Retinoid compositions and methods of use

Abstract

Described herein are retinoid compositions, and methods of using such retinoid compositions for treating ocular conditions including macular degeneration, the retinoid compositions comprising (a) a retinoid, preferably a C20-deuterated vitamin A, the retinoid inhibiting dimerization to N-retinyl-N-retinylidene ethanolamine (A2E); (b) a lipid excipient, preferably an omega-3 fatty acid including eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA); and (c) a surfactant, wherein the composition increases bioavailability of the retinoid in a subject.

Description

[0001] Cross-referencing This application claims the benefit of Australian application number 2024900129, filed on 19 January 2024, the entire contents of which are incorporated herein by reference.

[0002] Overview Retinoids, such as vitamin A, can be used to treat diseases or conditions, such as eye diseases or eye conditions. For example, by administering retinoids to a subject, the abundance of lipofuscin in the subject decreases, thereby treating eye diseases or eye conditions associated with the accumulation of lipofuscin or N-retinyl-N-retinylethanolamine (A2E) in the subject's eyes. Retinoids can also be used for non-medical purposes, such as for aesthetic, cosmetic, or supplement purposes.

[0003] However, the use of retinoids has drawbacks. For example, administering excessive doses of retinoids to subjects can lead to hypervitaminosis. On the other hand, ensuring adequate bioavailability of retinoids delivered to the desired sites in subjects remains an ongoing challenge. For instance, retinoids are not readily soluble in aqueous environments, making their formulation and administration to subjects difficult.

[0004] Therefore, there remains a need for compositions and methods for delivering retinoids to subjects in amounts that ensure adequate bioavailability. There also remains a need for compositions and methods that utilize retinoids for the treatment of diseases or conditions or for non-medical purposes (e.g., aesthetic, cosmetic, or supplemental).

[0005] The aspects disclosed herein provide a composition comprising: retinoids having a structure of formula I: The composition contains: a lipid excipient; and a surfactant, wherein retinoids are present in the composition at a percentage (w / w) of about 0.1% to about 90%. In some embodiments, the retinoids comprise the structure of formula I: In this system, each of the numbers 1 to 20 represents a position of a carbon atom covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronide), or R6 (CH2OCHOCH3 or retinyl acetate). In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at position 19 or at position 20. In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at position 19 or position 20, said position 19 comprising three hydrogen atoms replacing three hydrogen atoms (19, 19, 19-trideuterated retinol), and said position 20 comprising three hydrogen atoms replacing three hydrogen atoms (20, 20, 20-trideuterated retinol). In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at both positions 19 and 20, said position 19 comprising three hydrogen atoms replacing three hydrogen atoms, and said position 20 comprising three hydrogen atoms replacing three hydrogen atoms. In some embodiments, 19, 19, 19-trideuterated retinol comprises 19, 19, 19-trideuterated retinol analogs. In some embodiments, the 19,19,19-trideuterated retinol analogues comprise 19,19,19-trideuterated retinol esters. In some embodiments, the 19,19,19-trideuterated retinol analogues comprise 19,19,19-trideuterated retinol acetate. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol analogues. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol esters. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 19 and 20, wherein position 19 comprises replacing three hydrogen atoms with three deuterium atoms, and position 20 comprises replacing three hydrogen atoms with three deuterium atoms (19, 19, 19, 20, 20, 20-hexadeuterated retinol). In some embodiments, 19, 19, 19, 20, 20, 20-hexadeuterated retinol comprises 19, 19, 19, 20, 20, 20-hexadeuterated retinol analogs.In some embodiments, the 19,19,19,20,20,20-hexadeuterated retinoid analogues include 19,19,19,20,20,20-hexadeuterated retinoid esters. In some embodiments, the 19,19,19,20,20,20-hexadeuterated retinoid analogues include 19,19,19,20,20,20-hexadeuterated retinoid acetate. In some embodiments, the composition comprises from about 1.0 mg to about 5.0 mg of retinoids. In some embodiments, the composition comprises from about 2.0 mg to about 3.0 mg of retinoids. In some embodiments, the composition comprises about 2.5 mg of retinoids. In some embodiments, the lipid excipient comprises an ω-3 fatty acid. In some embodiments, the omega-3 fatty acid includes eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). In some embodiments, the omega-3 fatty acid includes both EPA and DHA. In some embodiments, the composition contains from about 100 mg to about 500 mg of EPA. In some embodiments, the composition contains from about 200 mg to about 400 mg of EPA. In some embodiments, the composition contains about 300 mg of EPA. In some embodiments, the composition contains from about 50 mg to about 200 mg of DHA. In some embodiments, the composition contains from about 100 mg to about 150 mg of DHA. In some embodiments, the composition contains about 110 mg of DHA. In some embodiments, the composition contains at least one additional ingredient. In some embodiments, at least one additional ingredient includes an antioxidant. In some embodiments, the antioxidant includes vitamin C, vitamin E, zinc, or grape seed extract. In some embodiments, at least one additional ingredient includes a curcumin compound. In some embodiments, at least one additional ingredient includes curcuminoids. In some embodiments, the composition contains from about 20 mg to about 100 mg of curcuminoids. In some embodiments, the composition comprises about 50 mg of curcumin. In some embodiments, at least one additional ingredient comprises a carotenoid. In some embodiments, the carotenoid comprises lutein, zeaxanthin, or astaxanthin. In some embodiments, the carotenoid comprises both lutein and zeaxanthin. In some embodiments, the composition comprises from about 1 mg to about 100 mg of lutein. In some embodiments, the composition comprises about 10 mg of lutein. In some embodiments, the composition comprises from about 1 mg to about 10 mg of zeaxanthin. In some embodiments, the composition comprises about 2 mg of zeaxanthin. In some embodiments, at least one additional ingredient comprises a flavonoid. In some embodiments, the flavonoid comprises anthocyanins. In some embodiments, at least one additional ingredient comprises an amino acid.In some embodiments, the amino acid includes taurine. In some embodiments, at least one additional component includes an emulsifier. In some embodiments, the surfactant includes Tween, Kolliphor, Labrasol, Gelucire, Capmul, polyethylene glycol (PEG), Transcutol, Capryol, or combinations thereof. In some embodiments, the surfactant consists of Gelucire, Capmul, Tween, and PEG. In some embodiments, Gelucire includes Gelucire 44 / 14. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Gelucire. In some embodiments, the composition contains about 0.1 mL of Gelucire. In some embodiments, Capmul includes Capmul MCM. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Capmul. In some embodiments, the composition contains about 0.1 mL of Capmul. In some embodiments, Tween includes Tween 80. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Tween. In some embodiments, the composition contains about 0.3 mL of Tween. In some embodiments, the PEG includes PEG 400. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of PEG. In some embodiments, the composition contains about 0.1 mL of PEG. In some embodiments, Kolliphor includes Kolliphor EL. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Kolliphor. In some embodiments, the composition contains about 0.3 mL of Kolliphor. In some embodiments, Transcutol includes Transcutol HP. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Transcutol. In some embodiments, the composition contains about 0.1 mL of Transcutol. In some embodiments, the composition is formulated as a semi-solid. In some embodiments, the composition is formulated as a soft gel capsule. In some embodiments, the composition is formulated as a solid dispersion. In some embodiments, the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof. In some embodiments, the composition is formulated for ocular application to a subject. In some embodiments, the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in the subject. In some embodiments, the composition modulates gene expression in retinal pigment epithelial (RPE) cells. In some embodiments, the composition increases the bioavailability of retinoids delivered to RPE cells.In some embodiments, bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability of retinol delivered to RPE cells without lipid excipients or surfactants. In some embodiments, the composition increases the bioavailability of retinol in a subject compared to the second bioavailability of retinol in a comparable composition without lipid excipients or surfactants. In some embodiments, bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability in a subject. In some embodiments, the composition does not decrease the bioavailability of retinol in a subject compared to the second bioavailability of retinol in a comparable composition without lipid excipients or surfactants. In some embodiments, bioavailability and second bioavailability are determined by the plasma concentration of retinol obtained from the subject. In some embodiments, the composition increases the stability of retinol compared to the second stability of retinol in a comparable composition without lipid excipients or surfactants. In some embodiments, the stability of retinoids is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second stability of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the composition increases the solubility of retinoids compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the solubility of retinoids is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 0.5% to about 90%. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%. In some embodiments, the composition also comprises an oil. In some embodiments, the oil includes corn oil, oleic acid, Maisine cc, or combinations thereof.

[0006] The aspects disclosed herein provide a method for treating an ocular disease or condition in a subject, the method comprising administering a composition comprising: retinoids; a lipid excipient; and a surfactant, wherein the lipid excipient increases the bioavailability of retinoids in the subject by at least 10% compared to the second bioavailability of retinoids formulated with an excipient different from the lipid excipient. In some embodiments, the retinoids comprise the structure of formula I: Formula I, wherein each of the numbers 1 to 20 represents a position of a carbon covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronide), or R6 (CH2OCHOCH3 or retinyl acetate). In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at position 19 or at position 20. In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at position 19 or position 20, said position 19 comprising three hydrogen atoms replacing three hydrogen atoms (19, 19, 19-trideuterated retinol), and said position 20 comprising three hydrogen atoms replacing three hydrogen atoms (20, 20, 20-trideuterated retinol). In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at both positions 19 and 20, said position 19 comprising three hydrogen atoms replacing three hydrogen atoms, and said position 20 comprising three hydrogen atoms replacing three hydrogen atoms. In some embodiments, 19, 19, 19-trideuterated retinol comprises 19, 19, 19-trideuterated retinol analogs. In some embodiments, the 19,19,19-trideuterated retinol analogues comprise 19,19,19-trideuterated retinol esters. In some embodiments, the 19,19,19-trideuterated retinol analogues comprise 19,19,19-trideuterated retinol acetate. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol analogues. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol esters. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 19 and 20, wherein position 19 comprises replacing three hydrogen atoms with three deuterium atoms, and position 20 comprises replacing three hydrogen atoms with three deuterium atoms (19, 19, 19, 20, 20, 20-hexadeuterated retinol). In some embodiments, 19, 19, 19, 20, 20, 20-hexadeuterated retinol comprises 19, 19, 19, 20, 20, 20-hexadeuterated retinol analogs.In some embodiments, the 19,19,19,20,20,20-hexadeuterated retinoid analogues include 19,19,19,20,20,20-hexadeuterated retinoid esters. In some embodiments, the 19,19,19,20,20,20-hexadeuterated retinoid analogues include 19,19,19,20,20,20-hexadeuterated retinoid acetate. In some embodiments, the composition comprises from about 1.0 mg to about 5.0 mg of retinoids. In some embodiments, the composition comprises from about 2.0 mg to about 3.0 mg of retinoids. In some embodiments, the composition comprises about 2.5 mg of retinoids. In some embodiments, the lipid excipient comprises an ω-3 fatty acid. In some embodiments, the omega-3 fatty acid includes eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). In some embodiments, the omega-3 fatty acid includes both EPA and DHA. In some embodiments, the composition contains from about 100 mg to about 500 mg of EPA. In some embodiments, the composition contains from about 200 mg to about 400 mg of EPA. In some embodiments, the composition contains about 300 mg of EPA. In some embodiments, the composition contains from about 50 mg to about 200 mg of DHA. In some embodiments, the composition contains from about 100 mg to about 150 mg of DHA. In some embodiments, the composition contains about 110 mg of DHA. In some embodiments, the composition contains at least one additional ingredient. In some embodiments, at least one additional ingredient includes an antioxidant. In some embodiments, the antioxidant includes vitamin C, vitamin E, zinc, or grape seed extract. In some embodiments, at least one additional ingredient includes a curcumin compound. In some embodiments, at least one additional ingredient includes curcuminoids. In some embodiments, the composition contains from about 20 mg to about 100 mg of curcuminoids. In some embodiments, the composition comprises about 50 mg of curcumin. In some embodiments, at least one additional ingredient comprises a carotenoid. In some embodiments, the carotenoid comprises lutein, zeaxanthin, or astaxanthin. In some embodiments, the carotenoid comprises both lutein and zeaxanthin. In some embodiments, the composition comprises from about 1 mg to about 100 mg of lutein. In some embodiments, the composition comprises about 10 mg of lutein. In some embodiments, the composition comprises from about 1 mg to about 10 mg of zeaxanthin. In some embodiments, the composition comprises about 2 mg of zeaxanthin. In some embodiments, at least one additional ingredient comprises a flavonoid. In some embodiments, the flavonoid comprises anthocyanins. In some embodiments, at least one additional ingredient comprises an amino acid.In some embodiments, the amino acid includes taurine. In some embodiments, at least one additional component includes an emulsifier. In some embodiments, the surfactant includes Tween, Kolliphor, Labrasol, Gelucire, Capmul, polyethylene glycol (PEG), Transcutol, Capryol, or combinations thereof. In some embodiments, the surfactant consists of Gelucire, Capmul, Tween, and PEG. In some embodiments, Gelucire includes Gelucire 44 / 14. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Gelucire. In some embodiments, the composition contains about 0.1 mL of Gelucire. In some embodiments, Capmul includes Capmul MCM. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Capmul. In some embodiments, the composition contains about 0.1 mL of Capmul. In some embodiments, Tween includes Tween 80. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Tween. In some embodiments, the composition contains about 0.3 mL of Tween. In some embodiments, the PEG includes PEG 400. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of PEG. In some embodiments, the composition contains about 0.1 mL of PEG. In some embodiments, Kolliphor includes Kolliphor EL. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Kolliphor. In some embodiments, the composition contains about 0.3 mL of Kolliphor. In some embodiments, Transcutol includes Transcutol HP. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Transcutol. In some embodiments, the composition contains about 0.1 mL of Transcutol. In some embodiments, the composition is formulated as a semi-solid. In some embodiments, the composition is formulated as a soft gel capsule. In some embodiments, the composition is formulated as a solid dispersion. In some embodiments, the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof. In some embodiments, the composition is formulated for ocular application to a subject. In some embodiments, the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in the subject. In some embodiments, the composition modulates gene expression in retinal pigment epithelial (RPE) cells. In some embodiments, the composition increases the bioavailability of retinoids delivered to RPE cells.In some embodiments, bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability of retinol delivered to RPE cells without lipid excipients or surfactants. In some embodiments, the composition increases the bioavailability of retinol in a subject compared to the second bioavailability of retinol in a comparable composition without lipid excipients or surfactants. In some embodiments, bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability in a subject. In some embodiments, the composition does not decrease the bioavailability of retinol in a subject compared to the second bioavailability of retinol in a comparable composition without lipid excipients or surfactants. In some embodiments, bioavailability and second bioavailability are determined by the plasma concentration of retinol obtained from the subject. In some embodiments, the composition increases the stability of retinol compared to the second stability of retinol in a comparable composition without lipid excipients or surfactants. In some embodiments, the stability of retinoids is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second stability of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the composition increases the solubility of retinoids compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the solubility of retinoids is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 0.5% to about 90%. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%. In some embodiments, the composition also comprises an oil. In some embodiments, the oil includes corn oil, oleic acid, Maisine cc, or combinations thereof. In some embodiments, the ocular disease or condition is associated with the accumulation of N-sub-retinyl-N-retinylethanolamine (A2E). In some embodiments, the method further includes reducing the accumulation of A2E in the subject. In some embodiments, the ocular disease or condition is associated with retinal pigment epithelium (RPE) cells. In some embodiments, the method further includes regulating gene expression in RPE cells. In some embodiments, gene expression includes the expression of ATP-binding box subfamily A (ABC1) member 4 (ABCA4), elongation of very long chain fatty acids protein 4 (ELOVL4), or a combination thereof.In some embodiments, the ocular disease or condition is macular degeneration. In some embodiments, macular degeneration includes age-related macular degeneration (AMD), bestrophinopathies, bull's eyemaculopathy, central serous retinopathy, Charles-Bunnet syndrome (CBS), cone dystrophy, Doyne's cellulopathy, diabetic macular edema (DMO), macular hole, macular edema, myopic macular degeneration, pattern dystrophy, pseudoxanthoma elastica (PXE), punctate intrachoroidal lesions (PIC), retinal vein occlusion (RVO), Sorsby fundus dystrophy, Stargardt disease, geographic atrophy, or combinations thereof. In some embodiments, AMD includes dry AMD. In some embodiments, AMD includes early AMD. In some embodiments, AMD includes wet AMD.

[0007] The aspects disclosed herein provide for use of the composition, which includes contacting a subject with the composition comprising: retinoids; a lipid excipient; and a surfactant, wherein the lipid excipient increases the bioavailability of retinoids in a subject by at least 10% compared to the second bioavailability of retinoids formulated with an excipient different from the lipid excipient, and wherein the use is for non-medical purposes. In some embodiments, the retinoids comprise the structure of formula I: In this system, each of the numbers 1 to 20 represents a position of a carbon atom covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), or R5 (COO-glucuronide). In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at position 19 or at position 20. In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at position 19 or position 20, said position 19 comprising three hydrogen atoms replacing three hydrogen atoms (19, 19, 19-trideuterated retinol), said position 20 comprising three hydrogen atoms replacing three hydrogen atoms (20, 20, 20-trideuterated retinol). In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at both positions 19 and 20, said position 19 comprising three hydrogen atoms replacing three hydrogen atoms, said position 20 comprising three hydrogen atoms replacing three hydrogen atoms. In some embodiments, 19, 19, 19-trideuterated retinol comprises 19, 19, 19-trideuterated retinol analogs. In some embodiments, the 19,19,19-trideuterated retinol analogues comprise 19,19,19-trideuterated retinol esters. In some embodiments, the 19,19,19-trideuterated retinol analogues comprise 19,19,19-trideuterated retinol acetate. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol analogues. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol esters. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 19 and 20, wherein position 19 comprises replacing three hydrogen atoms with three deuterium atoms, and position 20 comprises replacing three hydrogen atoms with three deuterium atoms (19, 19, 19, 20, 20, 20-hexadeuterated retinol). In some embodiments, 19, 19, 19, 20, 20, 20-hexadeuterated retinol comprises 19, 19, 19, 20, 20, 20-hexadeuterated retinol analogs. In some embodiments, 19, 19, 19, 20, 20, 20-hexadeuterated retinol analogs comprise 19, 19, 19, 20, 20, 20-hexadeuterated retinol esters.In some embodiments, the 19,19,19,20,20,20-hexadeuterated retinoid analogues include 19,19,19,20,20,20-hexadeuterated retinoid acetate. In some embodiments, the composition comprises from about 1.0 mg to about 5.0 mg of retinoids. In some embodiments, the composition comprises from about 2.0 mg to about 3.0 mg of retinoids. In some embodiments, the composition comprises about 2.5 mg of retinoids. In some embodiments, the lipid excipient comprises an omega-3 fatty acid. In some embodiments, the omega-3 fatty acid comprises EPA or DHA. In some embodiments, the omega-3 fatty acid comprises both EPA and DHA. In some embodiments, the composition comprises from about 100 mg to about 500 mg of EPA. In some embodiments, the composition comprises from about 200 mg to about 400 mg of EPA. In some embodiments, the composition comprises about 300 mg of EPA. In some embodiments, the composition contains from about 50 mg to about 200 mg of DHA. In some embodiments, the composition contains from about 100 mg to about 150 mg of DHA. In some embodiments, the composition contains about 110 mg of DHA. In some embodiments, the composition contains at least one additional ingredient. In some embodiments, at least one additional ingredient includes an antioxidant. In some embodiments, the antioxidant includes vitamin C, vitamin E, zinc, or grape seed extract. In some embodiments, at least one additional ingredient includes a curcumin compound. In some embodiments, at least one additional ingredient includes curcuminoids. In some embodiments, the composition contains from about 20 mg to about 100 mg of curcuminoids. In some embodiments, the composition contains about 50 mg of curcuminoids. In some embodiments, at least one additional ingredient includes a carotenoid. In some embodiments, the carotenoid includes lutein, zeaxanthin, or astaxanthin. In some embodiments, the composition contains from about 1 mg to about 100 mg of lutein. In some embodiments, the composition contains about 10 mg of lutein. In some embodiments, the composition comprises from about 1 mg to about 10 mg of zeaxanthin. In some embodiments, the composition comprises about 2 mg of zeaxanthin. In some embodiments, at least one additional component comprises a flavonoid. In some embodiments, the flavonoid comprises anthocyanins. In some embodiments, at least one additional component comprises an amino acid. In some embodiments, the amino acid comprises taurine. In some embodiments, at least one additional component comprises an emulsifier. In some embodiments, the surfactant comprises Tween, Kolliphor, Labrasol, Gelucire, Capmul, PEG, Transcutol, Capryol, or combinations thereof.In some embodiments, the surfactant comprises Gelucire, Capmul, Tween, and PEG. In some embodiments, Gelucire includes Gelucire 44 / 14. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Gelucire. In some embodiments, the composition contains about 0.1 mL of Gelucire. In some embodiments, Capmul includes Capmul MCM. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Capmul. In some embodiments, the composition contains about 0.1 mL of Capmul. In some embodiments, Tween includes Tween 80. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of Tween. In some embodiments, the composition contains about 0.3 mL of Tween. In some embodiments, the PEG includes PEG 400. In some embodiments, the composition contains from about 0.05 mL to about 0.5 mL of PEG. In some embodiments, the composition contains about 0.1 mL of PEG. In some embodiments, Kolliphor includes Kolliphor EL. In some embodiments, the composition comprises from about 0.05 mL to about 0.5 mL of Kolliphor. In some embodiments, the composition comprises about 0.3 mL of Kolliphor. In some embodiments, Transcutol comprises Transcutol HP. In some embodiments, the composition comprises from about 0.05 mL to about 0.5 mL of Transcutol. In some embodiments, the composition comprises about 0.1 mL of Transcutol. In some embodiments, the composition is formulated as a semi-solid. In some embodiments, the composition is formulated as a soft gel capsule. In some embodiments, the composition is formulated as a solid dispersion. In some embodiments, the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof. In some embodiments, the composition is formulated for ocular application to a subject. In some embodiments, the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in a subject. In some embodiments, the composition modulates gene expression in retinal pigment epithelial (RPE) cells. In some embodiments, the composition increases the bioavailability of retinoids delivered to RPE cells. In some embodiments, bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability of delivering retinoids to RPE cells without lipid excipients or surfactants.In some embodiments, the composition increases the stability of retinoids compared to the second stability of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the stability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second stability of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the composition increases the bioavailability of retinoids in a subject compared to the second bioavailability of retinoids in a comparable composition without lipid excipients or surfactants. In some embodiments, the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability in a subject. In some embodiments, the composition does not decrease the bioavailability of retinoids in a subject compared to the second bioavailability of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, bioavailability and second bioavailability are determined by the plasma concentration of retinoids obtained from the subject. In some embodiments, the composition increases the solubility of retinoids compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the solubility is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 0.5% to about 90%. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%. In some embodiments, the composition comprises an oil. In some embodiments, the oil includes corn oil, oleic acid, Maisine cc, or combinations thereof. In some embodiments, the use is for aesthetic purposes. In some embodiments, the use is for cosmetic purposes. In some embodiments, the use is for supplementary purposes. In some embodiments, the use is not for treating a disease or condition. In some embodiments, the composition is formulated for transdermal delivery of retinoids to a subject. In some embodiments, the composition is formulated as a semi-solid. In some embodiments, the composition is formulated as a soft gel capsule. In some embodiments, the composition is formulated as a solid dispersion. In some embodiments, the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof. In some embodiments, the composition is formulated as a supplement.

[0008] Among the various embodiments disclosed herein, a composition is provided comprising: retinoids; and a lipid excipient, wherein the retinoids are present in the composition in a percentage (w / w) of about 0.1% to about 90%.

[0009] In some implementations, retinoids include the structure of formula I: In this system, each of the numbers 1 to 20 represents a position of a carbon atom covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronide), or R6 (CH2OCHOCH3 or retinyl acetate). In some embodiments, the position of the carbon atom substituted with at least one hydrogen atom is at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the position of the carbon atom substituted with at least one hydrogen atom is at position 20. In some embodiments, the position of the carbon atom substituted with at least one hydrogen atom is at position 20, wherein position 20 comprises the substitution of three hydrogen atom atom with three deuterium atom (20,20,20-trideuterated retinol). In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is substituted with at least one deuterium are located at positions 14 and 20, wherein position 14 comprises substituted one hydrogen atom with one deuterium, and position 20 comprises substituted three hydrogen atoms with three deuteriums (14,20,20,20-tetradeuterated retinol). In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol analogs. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol esters. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 12, 14, and 20, wherein position 12 comprises replacing one hydrogen atom with one deuterium, and position 20 comprises replacing three hydrogen atoms with three deuteriums (12, 14, 20, 20, 20-pentadeuterated retinol). In some embodiments, 12, 14, 20, 20, 20-pentadeuterated retinol comprises 12, 14, 20, 20, 20-pentadeuterated retinol analogs.In some embodiments, the 12,14,20,20,20-pentadeuterated retinol analogues include 12,14,20,20,20-pentadeuterated retinol esters. In some embodiments, the 12,14,20,20,20-pentadeuterated retinol analogues include 12,14,20,20,20-pentadeuterated retinol acetate.

[0010] In some embodiments, the composition is formulated as a semi-solid.

[0011] In some embodiments, the composition is formulated as a soft gel capsule.

[0012] In some embodiments, the composition is formulated as a solid dispersion.

[0013] In some embodiments, the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

[0014] In some embodiments, the composition comprises at least one additional ingredient. In some embodiments, at least one additional ingredient includes an antioxidant. In some embodiments, the antioxidant includes vitamin C, vitamin E, zinc, or grape seed extract. In some embodiments, at least one additional ingredient includes a fatty acid. In some embodiments, the fatty acid includes omega-3 fatty acids. In some embodiments, at least one additional ingredient includes a carotenoid. In some embodiments, the carotenoid includes lutein, zeaxanthin, or astaxanthin. In some embodiments, at least one additional ingredient includes flavonoids. In some embodiments, the flavonoid includes anthocyanins. In some embodiments, at least one additional ingredient includes an amino acid. In some embodiments, the amino acid includes taurine.

[0015] In some embodiments, the composition is formulated for ocular application to a subject.

[0016] In some embodiments, the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in the subject.

[0017] In some embodiments, the composition modulates gene expression in retinal pigment epithelial (RPE) cells. In some embodiments, the composition increases the bioavailability of retinoids delivered to RPE cells.

[0018] In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 0.5% to about 90%. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%.

[0019] Among the various embodiments disclosed herein, a method for treating an eye disease or eye condition in a subject is provided, the method comprising administering a composition comprising: retinoids; and a lipid excipient, wherein the lipid excipient increases the bioavailability of retinoids in the subject by at least 10% compared to the second bioavailability of retinoids formulated with an excipient different from the lipid excipient.

[0020] In some implementations, retinoids include the structure of formula I: Formula I, wherein each of the numbers 1 to 20 represents a position of a carbon covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronide), or R6 (CH2OCHOCH3 or retinyl acetate). In some embodiments, the position of the carbon with at least one hydrogen atom substituted with at least one deuterium atom is at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the position of the carbon with at least one hydrogen atom substituted with at least one deuterium atom is at position 20. In some embodiments, the position of the carbon with at least one hydrogen atom substituted with at least one deuterium atom is at position 20, wherein position 20 comprises three hydrogen atoms substituted with three deuterium atoms (20, 20, 20-trideuterated retinol). In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol acetate. In some embodiments, the carbons at positions 14 and 20 are substituted with at least one deuterium, wherein position 14 comprises substituted one hydrogen atom with one deuterium, and position 20 comprises substituted three hydrogen atoms with three deuteriums (14,20,20,20-tetradeuterated retinol). In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol analogs. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol esters. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 12, 14, and 20, wherein position 12 comprises replacing one hydrogen atom with one deuterium, and position 20 comprises replacing three hydrogen atoms with three deuteriums (12, 14, 20, 20, 20-pentadeuterated retinol). In some embodiments, 12, 14, 20, 20, 20-pentadeuterated retinol comprises 12, 14, 20, 20, 20-pentadeuterated retinol analogs.In some embodiments, the 12,14,20,20,20-pentadeuterated retinol analogues include 12,14,20,20,20-pentadeuterated retinol esters. In some embodiments, the 12,14,20,20,20-pentadeuterated retinol analogues include 12,14,20,20,20-pentadeuterated retinol acetate.

[0021] In some embodiments, the composition is formulated as a semi-solid.

[0022] In some embodiments, the composition is formulated as a soft gel capsule.

[0023] In some embodiments, the composition is formulated as a solid dispersion.

[0024] In some embodiments, the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

[0025] In some embodiments, the composition comprises at least one additional ingredient. In some embodiments, at least one additional ingredient includes an antioxidant. In some embodiments, the antioxidant includes vitamin C, vitamin E, zinc, or grape seed extract. In some embodiments, at least one additional ingredient includes a fatty acid. In some embodiments, the fatty acid includes omega-3 fatty acids. In some embodiments, at least one additional ingredient includes a carotenoid. In some embodiments, the carotenoid includes lutein, zeaxanthin, or astaxanthin. In some embodiments, at least one additional ingredient includes a flavonoid. In some embodiments, the flavonoid includes anthocyanins. In some embodiments, at least one additional ingredient includes an amino acid. In some embodiments, the amino acid includes taurine. In some embodiments, the composition is formulated for ocular application to a subject.

[0026] In some implementations, eye diseases or eye conditions are associated with the accumulation of N-sub-retinyl-N-retinylethanolamine (A2E).

[0027] In some implementations, the method also includes reducing the accumulation of A2E in the subject.

[0028] In some embodiments, eye diseases or conditions are associated with retinal pigment epithelial (RPE) cells. In some embodiments, the method also includes regulating gene expression in RPE cells.

[0029] In some implementations, gene expression includes the expression of ATP-binding box subfamily A (ABC1) member 4 (ABCA4), very long chain fatty acid extension protein 4 (ELOVL4), or a combination thereof.

[0030] In some implementations, the eye disease or condition is macular degeneration.

[0031] In some embodiments, macular degeneration includes age-related macular degeneration (AMD), vitrectomycosis, bull's-eye macular degeneration, central serous retinopathy, Charles-Bonnett syndrome (CBS), cone dystrophy, Doyne's cellulopathy, diabetic macular edema (DMO), macular hole, macular edema, myopic macular degeneration, pattern dystrophy, pseudoxanthoma elastica (PXE), punctate intrachorioretinopathy (PIC), retinal vein occlusion (RVO), Sotheby's dystrophy, Staggart's disease, geographic atrophy, or combinations thereof. In some embodiments, AMD includes dry AMD. In some embodiments, AMD includes early AMD. In some embodiments, AMD includes wet AMD.

[0032] In some implementations, lipid excipients increase the bioavailability of retinoids in subjects by at least 50% compared to the second bioavailability of retinoids formulated with excipients different from lipid excipients.

[0033] In some embodiments, the lipid excipient increases the bioavailability of retinoids in subjects by 100% compared to the second bioavailability of retinoids formulated with excipients different from lipid excipients. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%.

[0034] In various embodiments disclosed herein, use of the composition is provided, the use including contacting a subject with the composition comprising: retinoids; and a lipid excipient, wherein the lipid excipient increases the bioavailability of retinoids in a subject by at least 10% compared to the second bioavailability of retinoids formulated with an excipient different from the lipid excipient, and wherein the use is for non-medical purposes.

[0035] In some implementations, retinoids include the structure of formula I: Formula I, wherein each of the numbers 1 to 20 represents a position of a carbon covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), or R5 (COO-glucuronide). In some embodiments, the position of the carbon atom substituted with at least one hydrogen atom is at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the position of the carbon atom substituted with at least one hydrogen atom is at position 20. In some embodiments, the position of the carbon atom substituted with at least one hydrogen atom is at position 20, wherein position 20 comprises the substitution of three hydrogen atom with three deuterium atom. In some embodiments, the position of the carbon atom substituted with at least one hydrogen atom is at position 20, wherein position 20 comprises the substitution of three hydrogen atom with three deuterium atom (20,20,20-trideuterated retinol). In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is substituted with at least one deuterium are located at positions 14 and 20, wherein position 14 comprises substituted one hydrogen atom with one deuterium, and position 20 comprises substituted three hydrogen atoms with three deuteriums (14,20,20,20-tetradeuterated retinol). In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol analogs. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol esters. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 12, 14, and 20, wherein position 12 comprises replacing one hydrogen atom with one deuterium, and position 20 comprises replacing three hydrogen atoms with three deuteriums (12, 14, 20, 20, 20-pentadeuterated retinol). In some embodiments, 12, 14, 20, 20, 20-pentadeuterated retinol comprises 12, 14, 20, 20, 20-pentadeuterated retinol analogs.In some embodiments, the 12,14,20,20,20-pentadeuterated retinol analogues include 12,14,20,20,20-pentadeuterated retinol esters. In some embodiments, the 12,14,20,20,20-pentadeuterated retinol analogues include 12,14,20,20,20-pentadeuterated retinol acetate.

[0036] In some embodiments, the use is for aesthetic purposes. In some embodiments, the use is for cosmetic purposes. In some embodiments, the use is for supplementary purposes.

[0037] In some implementations, the purpose is not to treat diseases or conditions.

[0038] In some embodiments, the composition is formulated for transdermal delivery of retinoids to a subject.

[0039] In some embodiments, the composition is formulated as a semi-solid.

[0040] In some embodiments, the composition is formulated as a soft gel capsule.

[0041] In some embodiments, the composition is formulated as a solid dispersion.

[0042] In some embodiments, the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

[0043] In some embodiments, the composition comprises at least one additional ingredient. In some embodiments, at least one additional ingredient includes an antioxidant. In some embodiments, the antioxidant includes vitamin C, vitamin E, zinc, or grape seed extract. In some embodiments, at least one additional ingredient includes a fatty acid. In some embodiments, the fatty acid includes omega-3 fatty acids. In some embodiments, at least one additional ingredient includes a carotenoid. In some embodiments, the carotenoid includes lutein, zeaxanthin, or astaxanthin. In some embodiments, at least one additional ingredient includes flavonoids. In some embodiments, the flavonoid includes anthocyanins. In some embodiments, at least one additional ingredient includes an amino acid. In some embodiments, the amino acid includes taurine.

[0044] In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%. In some embodiments, lipid excipients increase the bioavailability of retinoids in subjects by 100% compared to the second bioavailability of retinoids formulated with excipients different from lipid excipients. In some embodiments, the composition is formulated as a supplement.

[0045] By incorporating references All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the extent that each individual publication, patent, or patent application is specifically and individually indicated to be incorporated by reference. In the event that any publication, patent, or patent application incorporated by reference contradicts the disclosure contained in this specification, this specification is intended to supersede and / or give precedence to any such contradictory material. Brief description of the attached diagram The novel features of this disclosure are set forth in particular in the appended claims. A better understanding of the features and advantages of this disclosure will be obtained by referring to the following detailed description (which sets forth illustrative embodiments utilizing the principles of this disclosure) and the accompanying drawings (which are also referred to herein as "Figures" and "FIGs"), in which: Figure 1 The figure shows a graph illustrating the linearity of the ultra-high performance liquid chromatography (UPLC) method for determination and analysis as disclosed herein.

[0047] Figure 2 The figure shows an image illustrating the appearance of the first round of lipid formulations, F01-F17.

[0048] Figure 3 The image shows the diluted appearance of the first-round lipid formulation without retinol-d6, diluted with simulated gastric juice (SGF) and FaSSIF.

[0049] Figure 4 The figure shows an image illustrating the diluted appearance of a first-round lipid formulation containing retinol-d6 diluted with SGF and FaSSIF.

[0050] Figure 5 The image shows what the second round of lipid formulations looks like.

[0051] Figure 6 The figure shows images illustrating the diluted appearance of the second-round lipid formulation without retinol-d6. In the dilution studies without retinol-d6 but containing lutein, zeaxanthin, and curcumin, F22 showed a good PDI. F18-F22 showed suspensions with a coarse-particle state after dilution with simulated gastric juice (SGF) and FaSSIF. PSD results were significantly affected by the presence of insoluble substances, resulting in multiple peaks and poor data quality. Therefore, lutein, zeaxanthin, and curcumin were excluded in the following dilution studies involving retinol-d6 to avoid their influence.

[0052] Figure 7 The figure shows the appearance of F23 and the diluted appearance of the second-round lipid formulation containing retinol-d6.

[0053] Figure 8 The figure shows an overlay of placebo and standard (STD) solutions.

[0054] Figure 9 The figure shows the time-series measurement of retinol-d3 plasma concentration over a 24-hour period.

[0055] The novel features of this disclosure are set forth in particular in the appended claims. A better understanding of the features and advantages of this disclosure will be obtained by referring to the detailed description of the following illustrative embodiments.

[0056] Detailed Explanation Retinoids can treat a variety of diseases or conditions. For example, retinoids can be administered to subjects with retinal defects. Such retinal defects can manifest as eye diseases or eye conditions. Retinoids can also be used for non-medical purposes, such as for aesthetic, cosmetic, or supplementary uses. However, frequent or excessive administration of retinoids can lead to toxicity, such as hypervitaminosis A syndrome, where symptoms of retinoid toxicity can include changes in lipid metabolism, liver damage, nausea, vomiting, blurred vision, or bone damage. Therefore, in some aspects, as described herein, a composition is provided comprising: retinoids; and a lipid excipient. In some embodiments, retinoids are present in the composition at a percentage (weight / weight or w / w) of about 10% to about 90%. In some embodiments, retinoids are present in the composition at a percentage (weight / weight or w / w) of about 1% to about 50%. In some embodiments, retinoids comprise the structure of formula I: Formula I, where each number represents the position of a carbon covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronide), or R6 (CH2OCHOCH3 or retinyl acetate). In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at position 20. In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at position 20, wherein position 20 comprises three hydrogen atoms substituted with three deuterium atoms (20, 20, 20-trideuterated retinol). In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is substituted with at least one deuterium are located at positions 14 and 20, wherein position 14 comprises substituted one hydrogen atom with one deuterium, and position 20 comprises substituted three hydrogen atoms with three deuteriums (14,20,20,20-tetradeuterated retinol). In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol analogs. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol esters. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 12, 14, and 20, wherein position 12 comprises replacing one hydrogen atom with one deuterium, and position 20 comprises replacing three hydrogen atoms with three deuteriums (12, 14, 20, 20, 20-pentadeuterated retinol). In some embodiments, 12, 14, 20, 20, 20-pentadeuterated retinol comprises 12, 14, 20, 20, 20-pentadeuterated retinol analogs.In some embodiments, the 12,14,20,20,20-pentadeuterated retinoid analogues comprise 12,14,20,20,20-pentadeuterated retinoid esters. In some embodiments, the 12,14,20,20,20-pentadeuterated retinoid analogues comprise 12,14,20,20,20-pentadeuterated retinoid acetate. In some embodiments, the retinoids described herein comprise retinol-d6. In some embodiments, the retinoids described herein consist of retinol-d6. In some embodiments, the retinoids described herein comprise vitamin A-d6. In some embodiments, the retinoids described herein consist of vitamin A-d6. In some embodiments, the retinoids described herein comprise retinol-d3. In some embodiments, the retinoids described herein consist of retinol-d3. In some embodiments, the retinoids described herein comprise vitamin A-d3.

[0057] In some embodiments, the composition is formulated for the treatment of the ocular diseases or conditions described herein. In some embodiments, the composition is formulated with a lipid excipient, in part because retinoids are lipid-soluble molecules. In some embodiments, the composition containing retinoids may comprise an oil-based capsule (e.g., a soft gel capsule). In some embodiments, the composition comprises additional excipients to increase water solubility or retinoid bioavailability. For example, hydroxypropyl-β-cyclodextrin (HPBCD) or nanoparticles (e.g., lipid nanoparticles, nanomicelles, nanocapsules, nanospheres, or combinations thereof) may be added to the composition to increase: the abundance of retinoids in the composition or the retinoid bioavailability in a subject after administration of the composition to a subject. In some embodiments, the composition comprises retinoids, including deuterated retinoids. In some embodiments, the composition comprises at least one additional ingredient. In some embodiments, at least one additional ingredient is an antioxidant. In some embodiments, the composition is an oil-based formulation (e.g., a soft gel capsule). In some embodiments, the composition is a lipid-based formulation (e.g., lipid nanoparticles, amorphous solid dispersions, or lipid polymer mixtures). Example 1 provides a non-limiting example of the manufacture and composition of the compositions described herein. In some embodiments, the composition may be any of the formulations illustrated in Table 6 (e.g., any of F01-F17). For example, as illustrated in Table 6, in some embodiments, the composition may be formulations F01, F02, F03, F04, F05, F06, F07, F08, F09, F10, F11, F12, F13, F14, F15, F16, or F17. In some embodiments, the composition may be any of the formulations illustrated in Table 9 (e.g., any of F18-F22). For example, as illustrated in Table 9, in some embodiments, the composition may be formulations F18, F19, F20, F21, or F22.

[0058] In some aspects, this document describes a method for treating an ocular disease or ocular condition in a subject. In some embodiments, the method includes administering a composition comprising: retinoids; and a lipid excipient. In some embodiments, the lipid excipient increases the bioavailability of retinoids in a subject by at least 10% compared to the bioavailability of retinoids formulated with an excipient different from the lipid excipient. In some embodiments, the lipid excipient increases the bioavailability of retinoids in a subject by 100% compared to the bioavailability of retinoids formulated with an excipient different from the lipid excipient. In some embodiments, the increased bioavailability of retinoids increases the therapeutic efficacy for treating an ocular disease or ocular condition. In some embodiments, the increased bioavailability of retinoids reduces retinoid toxicity in a subject. In some embodiments, retinoids (e.g., deuterated vitamin A or vitamin A derivatives), when administered to a subject, can reduce the formation or abundance of vitamin A dimers in the subject. In some embodiments, retinoids (e.g., deuterated vitamin A or vitamin A derivatives), when administered to a subject, can reduce the formation or abundance of lipofuscin in the subject. In some embodiments, retinoids (e.g., deuterated vitamin A or vitamin A derivatives), when administered to a subject, can reduce the formation or abundance of N-retinyl-N-retinylethanolamine (A2E), a toxic compound that accumulates in the retinal pigment epithelium (RPE) cells of the eye. A2E is formed as a byproduct of the visual cycle, in which retinaldehyde (a vitamin A derivative) reacts with phosphatidylethanolamine in RPE cells to regulate the visual cycle and maintain retinal health. Retinoids can reduce the formation or abundance of A2E through several mechanisms, including the regulation of the visual cycle. Retinoids are an essential component of the visual cycle, the process by which light is converted into electrical signals in the retina. By regulating this cycle, retinoids can influence the production of toxic byproducts such as A2E. In addition, retinoids exhibit antioxidant properties that can help neutralize free radicals and reduce oxidative stress in cells. Oxidative stress is associated with the formation of A2E and other harmful compounds in the retina. Furthermore, retinoids can affect the function and metabolism of retinal pigment epithelial cells (RPEs). By maintaining the proper function of these cells, retinoids can potentially reduce the accumulation of A2E. Additionally, retinoids can regulate the gene expression of enzymes involved in the formation of A2E in RPE cells. In some embodiments, gene expression includes the expression of ATP-binding box subfamily A (ABC1) member 4 (ABCA4), very long chain fatty acid extended protein 4 (ELOVL4), or combinations thereof. In some embodiments, the ocular disease or condition to be treated with the compositions described herein includes macular degeneration, such as age-related macular degeneration (AMD).

[0059] In some aspects, the use of the compositions described herein is described. In some embodiments, the use is for non-medical purposes. In some embodiments, the use is not a method of treatment. In some embodiments, the use of the compositions does not treat the eye diseases or eye conditions described herein. In some embodiments, the use is for aesthetic purposes. In some embodiments, the use is for cosmetic purposes. In some embodiments, the use is for supplementary purposes.

[0060] Composition In some aspects, this document describes a composition comprising retinoids. In some embodiments, the composition comprises retinoids and a lipid excipient. In some embodiments, the composition comprises retinoids, a lipid excipient, and a surfactant. In some embodiments, the composition comprising a lipid excipient and a surfactant increases bioavailability, solubility, stability, or a combination thereof, compared to comparable compositions in which retinoids are formulated without a lipid excipient or surfactant. In some embodiments, the composition comprising a lipid excipient and a surfactant increases bioavailability, solubility, stability, or a combination thereof, compared to comparable compositions in which retinoids are formulated without a lipid excipient and a surfactant.

[0061] In some embodiments, retinoids are present in the composition at a percentage (w / w) from about 10% to about 90%. In some embodiments, the bioavailability of retinoids (e.g., the abundance of retinoids delivered to the desired site in the subject after administration of the composition) is increased compared to the bioavailability of retinoids formulated in the absence of lipid excipients. In some embodiments, the lipid excipients increase the bioavailability of retinoids by at least 10%, at least 20%, at least 50%, at least two times, at least five times, or at least ten times.

[0062] In some embodiments, retinoids comprise vitamin A derivatives. In some embodiments, vitamin A derivatives comprise deuterated vitamin A. In some embodiments, the vitamin A derivative is deuterated vitamin A. In some embodiments, deuterated vitamin A comprises hydrogen atoms substituted with deuterium. In some embodiments, deuterated vitamin A comprises one or more hydrogen atoms substituted with one or more deuterium atoms. In some embodiments, deuterated vitamin A comprises two or more hydrogen atoms substituted with two or more deuterium atoms. In some embodiments, deuterated vitamin A comprises three or more hydrogen atoms substituted with three or more deuterium atoms. In some embodiments, deuterated vitamin A comprises four or more hydrogen atoms substituted with four or more deuterium atoms. In some embodiments, deuterated vitamin A comprises five or more hydrogen atoms substituted with five or more deuterium atoms. In some embodiments, deuterated vitamin A comprises six or more hydrogen atoms substituted with six or more deuterium atoms. In some embodiments, deuterated vitamin A comprises seven or more hydrogen atoms substituted with seven or more deuterium atoms. In some embodiments, deuterated vitamin A comprises eight or more hydrogen atoms substituted with eight or more deuterium atoms. In some embodiments, deuterated vitamin A comprises hydrogen atoms substituted with deuterium atoms, wherein the substituted hydrogen atoms are covalently linked to two or more carbon atoms of the deuterated vitamin A. In some embodiments, deuterated vitamin A comprises two or more hydrogen atoms substituted with deuterium atoms, wherein the two or more substituted hydrogen atoms are covalently linked to two or more carbon atoms of the deuterated vitamin A. In some embodiments, vitamin A derivatives include retinyl esters, retinol, retinal, retinoic acid, or combinations thereof. In some embodiments, vitamin A derivatives include synthetic retinoids, such as adapalene.

[0063] In some embodiments, retinoids are present in the composition at a percentage (weight / weight or w / w) of about 10% to about 90%. In some embodiments, retinoids are present in the composition at a percentage (weight / weight or w / w) of about 1% to about 50%. In some embodiments, the retinoids comprise the structure of formula I: Formula I, wherein each of the numbers 1 to 20 represents a position of a carbon covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronide), or R6 (CH2OCHOCH3 or retinyl acetate). In some embodiments, the position of the carbon with at least one hydrogen atom substituted with at least one deuterium atom is at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the position of the carbon with at least one hydrogen atom substituted with at least one deuterium atom is at position 20. In some embodiments, the position of the carbon with at least one hydrogen atom substituted with at least one deuterium atom is at position 20, wherein position 20 comprises three hydrogen atoms substituted with three deuterium atoms (20, 20, 20-trideuterated retinol). In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol acetate. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol. In some embodiments, 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters. In some embodiments, 20,20,20-trideuterated retinoids comprise 20,20,20-trideuterated retinyl acetate. In some embodiments, 20,20,20-trideuterated retinoids comprise 20,20,20-trideuterated retinaldehyde. In some embodiments, 20,20,20-trideuterated retinoids comprise 20,20,20-trideuterated pro-vitamin A carotenoids. In some embodiments, the retinoids comprise the following structure: .

[0064] In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at position 19 or position 20. In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at position 19 or position 20, wherein position 19 comprises three hydrogen atoms replaced by three deuterium atoms (19, 19, 19-trideuterated retinol), and position 20 comprises three hydrogen atoms replaced by three deuterium atoms (20, 20, 20-trideuterated retinol). In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium atom is located at both position 19 and position 20, wherein position 19 comprises three hydrogen atoms replaced by three deuterium atoms, and position 20 comprises three hydrogen atoms replaced by three deuterium atoms.

[0065] In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 19 and 20, wherein position 19 comprises replacing three hydrogen atoms with three deuterium atoms, and position 20 comprises replacing three hydrogen atoms with three deuterium atoms (19, 19, 19, 20, 20, 20-hexadeuterated retinol or retinol-d6). In some embodiments, 19, 19, 19, 20, 20, 20-hexadeuterated retinol or retinol-d6 comprises the following structure: In some embodiments, 19,19,19, 20, 20, 20-hexadecimalized retinol comprises 19,19,19, 20, 20, 20-hexadecimalized retinol analogs. In some embodiments, 19,19,19, 20, 20, 20-hexadecimalized retinol analogs comprise 19,19,19,20, 20, 20-hexadecimalized retinol esters. In some embodiments, 19,19,19, 20, 20, 20-hexadecimalized retinol analogs comprise 19,19,19, 20, 20, 20-hexadecimalized retinol acetate. In some embodiments, 19,19,19,20,20,20-hexadeuterated retinol comprises 19,19,19,20,20,20-hexadeuterated retinol. In some embodiments, 19,19,19,20,20,20-hexadeuterated retinol comprises 19,19,19,20,20,20-hexadeuterated retinol ester. In some embodiments, 19,19,19,20,20,20-hexadeuterated retinol comprises 19,19,19,20,20,20-hexadeuterated retinol acetate. In some embodiments, 19,19,19,20,20,20-hexadeuterated retinoids include 19,19,19,20,20,20-hexadeuterated retinaldehyde. In some embodiments, 19,19,19,20,20,20-hexadeuterated retinoids include 19,19,19,20,20,20-hexadeuterated pro-vitamin A carotenoids.

[0066] In some embodiments, the carbon atom in which at least one hydrogen atom is replaced by at least one deuterium is located at positions 14 and 20, wherein position 14 comprises replacing one hydrogen atom with one deuterium atom, and position 20 comprises replacing three hydrogen atom atom with three deuterium atom (14, 20, 20, 20-tetradeuterated retinol). In some embodiments, 14, 20, 20, 20-tetradeuterated retinol comprises 14, 20, 20, 20-tetradeuterated retinol analogues. In some embodiments, 14, 20, 20, 20-tetradeuterated retinol comprises 14, 20, 20, 20-tetradeuterated retinol ester. In some embodiments, 14, 20, 20, 20-tetradeuterated retinol comprises 14, 20, 20, 20-tetradeuterated retinol acetate. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol acetate. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinol ester. In some embodiments, 14,20,20,20-tetradeuterium retinol comprises 14,20,20,20-tetradeuterium retinaldehyde. In some implementations, 14,20,20,20-tetradeuterated retinoids include 14,20,20,20-tetradeuterated pro-vitamin A carotenoids.

[0067] In some embodiments, the carbon atoms in which at least one hydrogen atom is substituted with at least one deuterium are located at positions 12, 14, and 20, wherein position 12 comprises substituted one hydrogen atom with one deuterium, and position 20 comprises substituted three hydrogen atoms with three deuterium atoms (12, 14, 20, 20, 20-pentadeuterated retinol). In some embodiments, 12, 14, 20, 20, 20-pentadeuterated retinol comprises 12, 14, 20, 20, 20-pentadeuterated retinol analogs. In some embodiments, 12, 14, 20, 20, 20-pentadeuterated retinol comprises 12, 14, 20, 20, 20-pentadeuterated retinol esters. In some embodiments, 12,14,20,20,20-pentadeuterated retinol comprises 12,14,20,20,20-pentadeuterated retinol acetate. In some embodiments, 12,14,20,20,20-pentadeuterated retinol comprises 12,14,20,20,20-pentadeuterated retinol. In some embodiments, 12,14,20,20,20-pentadeuterated retinol comprises 12,14,20,20,20-pentadeuterated retinol ester. In some embodiments, 12,14,20,20,20-pentadeuterated retinoids include 12,14,20,20,20-pentadeuterated retinyl acetate. In some embodiments, 12,14,20,20,20-pentadeuterated retinoids include 12,14,20,20,20-pentadeuterated retinaldehyde. In some embodiments, 12,14,20,20,20-pentadeuterated retinoids include 12,14,20,20,20-pentadeuterated pro-vitamin A carotenoids.

[0068] In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at position 19. In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at position 19, wherein position 19 comprises three hydrogen atoms replaced by three deuterium atoms (19, 19, 19-trideuterated retinol). In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium atom is located at positions 10 and 19, wherein position 10 comprises one hydrogen atom replaced by one deuterium atom, and position 19 comprises three hydrogen atoms replaced by three deuterium atoms (14, 20, 20, 20-tetradeuterated retinol). In some embodiments, 10, 19, 19, 19-tetradeuterated retinol comprises 10, 19, 19, 19-tetradeuterated retinol analogs. In some embodiments, 10,19,19,19-tetradeuterium retinol comprises 10,19,19,19-tetradeuterium retinol esters. In some embodiments, 10,19,19,19-tetradeuterium retinol comprises 10,19,19,19-tetradeuterium retinol acetate. In some embodiments, 10,19,19,19-tetradeuterium retinol comprises 10,19,19,19-tetradeuterium retinol. In some embodiments, 10,19,19,19-tetradeuterium retinol comprises 10,19,19,19-tetradeuterium retinol esters. In some embodiments, 10,19,19,19-tetradeuterium retinoids include 10,19,19,19-tetradeuterium retinyl acetate. In some embodiments, 10,19,19,19-tetradeuterium retinoids include 10,19,19,19-tetradeuterium retinaldehyde. In some embodiments, 10,19,19,19-tetradeuterium retinoids include 10,19,19,19-tetradeuterium pro-carotene.

[0069] In some embodiments, the retinoid containing the structure of Formula I comprises replacing one hydrogen atom with one deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least one hydrogen atom with at least one deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing two hydrogen atom with two deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least two hydrogen atom with at least two deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing three hydrogen atom with three deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least three hydrogen atom with at least three deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing four hydrogen atom with four deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least four hydrogen atom with at least four deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing five hydrogen atom with five deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least five hydrogen atom with at least five deuterium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing six hydrogen atoms with six deuterium atoms. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least six hydrogen atoms with at least six deuterium atoms. In some embodiments, the retinoid containing the structure of Formula I comprises replacing seven hydrogen atoms with seven deuterium atoms. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least seven hydrogen atoms with at least seven deuterium atoms. In some embodiments, the retinoid containing the structure of Formula I comprises replacing eight hydrogen atoms with eight deuterium atoms. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least eight hydrogen atoms with at least eight deuterium atoms. In some embodiments, the retinoid containing the structure of Formula I comprises replacing one hydrogen atom with one tritium atom. In some embodiments, the retinoid containing the structure of Formula I comprises replacing at least one hydrogen atom with at least one tritium atom.

[0070] In some embodiments, the retinoids described herein include derivatives or analogs of retinoic acid. In some embodiments, the retinoids include retinoic acid (all-trans retinoic acid). In some embodiments, the retinoids include adapalene. In some embodiments, the retinoids include tazarotene. In some embodiments, the retinoids include trifarotene. In some embodiments, the retinoids include alitretinoin. In some embodiments, the retinoids include bexarotene. In some embodiments, the retinoids include isotretinoin. In some embodiments, the retinoids include retinyl palmitate. In some embodiments, the retinoids include 9-cis-retinal analogs (e.g., QLT091001). In some embodiments, the retinoids include tamibarotene. In some embodiments, the retinoids include acitretin. In some embodiments, the retinoids include tararotene.

[0071] In some embodiments, the composition, when administered to a subject, imparts therapeutic efficacy to the subject for treating a disease or condition in the subject. In some embodiments, the disease or condition is associated with lipofuscin. In some embodiments, the disease or condition is associated with the accumulation of lipofuscin. In some embodiments, the disease or condition is associated with the presence or abundance of lipofuscin in retinal pigment epithelial (RPE) cells. In some embodiments, the disease or condition is associated with N-retinyl-N-retinylethanolamine (A2E). In some embodiments, the disease or condition is associated with the accumulation of A2E. In some embodiments, the disease or condition is associated with RPE cells. In some embodiments, the disease or condition is associated with the presence or abundance of A2E in RPE cells. In some embodiments, the disease or condition is macular degeneration. Non-limiting examples of macular degeneration include age-related macular degeneration (AMD), yolk sac macular degeneration, bull's eye macular degeneration, central serous retinopathy, Charles-Bonnett syndrome (CBS), cone dystrophy, Doyne cellulopathy, diabetic macular edema (DMO), macular hole, macular edema, myopic macular degeneration, pattern dystrophy, pseudoxanthoma elastica (PXE), punctate intrachorioretinopathy (PIC), retinal vein occlusion (RVO), Sotheby's dystrophy, or Staggart's disease.

[0072] In some embodiments, the composition reduces the accumulation of vitamin A dimer in the subject. In some embodiments, the composition reduces the accumulation of lipofuscin in the subject. In some embodiments, the composition modulates the expression of one or more genes associated with lipofuscin accumulation in the subject. In some embodiments, the composition reduces the accumulation of A2E in the subject. In some embodiments, the composition modulates the expression of one or more genes associated with A2E accumulation or retinoic acid metabolism in the subject. In some embodiments, the composition increases the bioavailability of retinoids delivered to RPE cells in the subject. In some embodiments, the composition reduces retinoid-related toxicity in the subject. For example, the subject does not exhibit or does exhibit reduced retinoid toxicity when administered the composition described herein compared to when the subject is administered retinoids in other formulations.

[0073] In some embodiments, the composition comprises at least one lipid excipient. In some embodiments, the at least one lipid excipient comprises an oil that dissolves or encapsulates retinoids. In some embodiments, the at least one lipid excipient comprises a lipid. For example, the lipid excipient may be a lipid used to formulate the composition as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof. In some embodiments, the at least one lipid excipient comprises an omega-3 fatty acid. In some embodiments, the omega-3 fatty acid comprises eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). In some embodiments, the composition comprises an omega-3 fatty acid, which includes EPA and DHA. In some embodiments, the composition comprises about 50 mg to about 1,000 mg of EPA. In some embodiments, the composition comprises about 50 mg to about 100 mg, about 50 mg to about 200 mg, about 50 mg to about 250 mg, about 50 mg to about 300 mg, about 50 mg to about 350 mg, about 50 mg to about 400 mg, about 50 mg to about 450 mg, about 50 mg to about 500 mg, about 50 mg to about 750 mg, or about 50 mg to about 1,000 mg of EPA. In some embodiments, the composition comprises about 100 mg to about 200 mg, about 100 mg to about 250 mg, about 100 mg to about 300 mg, about 100 mg to about 350 mg, about 100 mg to about 400 mg, about 100 mg to about 450 mg, about 100 mg to about 500 mg, about 100 mg to about 750 mg, or about 100 mg to about 1,000 mg of EPA. In some embodiments, the composition comprises about 200 mg to about 250 mg, about 200 mg to about 300 mg, about 200 mg to about 350 mg, about 200 mg to about 400 mg, about 200 mg to about 450 mg, about 200 mg to about 500 mg, about 200 mg to about 750 mg, or about 200 mg to about 1,000 mg of EPA. In some embodiments, the composition comprises about 250 mg to about 300 mg, about 250 mg to about 350 mg, about 250 mg to about 400 mg, about 250 mg to about 450 mg, about 250 mg to about 500 mg, about 250 mg to about 750 mg, or about 250 mg to about 1,000 mg of EPA. In some embodiments, the composition comprises about 300 mg to about 350 mg, about 300 mg to about 400 mg, about 300 mg to about 450 mg, about 300 mg to about 500 mg, about 300 mg to about 750 mg, or about 300 mg to about 1,000 mg of EPA.In some embodiments, the composition comprises about 350 mg to about 400 mg, about 350 mg to about 450 mg, about 350 mg to about 500 mg, about 350 mg to about 750 mg, or about 350 mg to about 1,000 mg of EPA. In some embodiments, the composition comprises about 400 mg to about 450 mg, about 400 mg to about 500 mg, about 400 mg to about 750 mg, or about 400 mg to about 1,000 mg of EPA. In some embodiments, the composition comprises about 500 mg to about 750 mg, about 500 mg to about 1,000 mg, or about 750 mg to about 1,000 mg of EPA. In some embodiments, the composition comprises about 50 mg, about 100 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 750 mg, or about 1,000 mg of EPA. In some embodiments, the composition comprises at least about 50 mg, at least about 100 mg, at least about 200 mg, at least about 250 mg, at least about 300 mg, at least about 350 mg, at least about 400 mg, at least about 450 mg, at least about 500 mg, or at least about 750 mg of EPA. In some embodiments, the composition comprises up to about 100 mg, up to about 200 mg, up to about 250 mg, up to about 300 mg, up to about 350 mg, up to about 400 mg, up to about 450 mg, up to about 500 mg, up to about 750 mg, or up to about 1,000 mg of EPA.

[0074] In some embodiments, the composition comprises about 50 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 50 mg to about 110 mg, about 50 mg to about 120 mg, about 50 mg to about 130 mg, about 50 mg to about 140 mg, about 50 mg to about 150 mg, about 50 mg to about 200 mg, about 50 mg to about 250 mg, about 50 mg to about 300 mg, about 50 mg to about 350 mg, about 50 mg to about 400 mg, or about 50 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 110 mg to about 120 mg, about 110 mg to about 130 mg, about 110 mg to about 140 mg, about 110 mg to about 150 mg, about 110 mg to about 200 mg, about 110 mg to about 250 mg, about 110 mg to about 300 mg, about 110 mg to about 350 mg, about 110 mg to about 300 mg, or about 110 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 120 mg to about 130 mg, about 120 mg to about 140 mg, about 120 mg to about 150 mg, about 120 mg to about 200 mg, about 120 mg to about 250 mg, about 120 mg to about 300 mg, about 120 mg to about 350 mg, about 120 mg to about 400 mg, or about 120 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 130 mg to about 140 mg, about 130 mg to about 150 mg, about 130 mg to about 200 mg, about 130 mg to about 250 mg, about 130 mg to about 300 mg, about 130 mg to about 350 mg, about 130 mg to about 400 mg, or about 130 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 150 mg to about 200 mg, about 150 mg to about 250 mg, about 150 mg to about 300 mg, about 150 mg to about 350 mg, about 150 mg to about 400 mg, or about 150 mg to about 500 mg of DHA.In some embodiments, the composition comprises about 200 mg to about 250 mg, about 200 mg to about 300 mg, about 200 mg to about 350 mg, about 200 mg to about 400 mg, or about 200 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 250 mg to about 300 mg, about 250 mg to about 350 mg, about 250 mg to about 400 mg, or about 250 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 300 mg to about 350 mg, about 300 mg to about 400 mg, or about 300 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 350 mg to about 400 mg, or about 350 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 400 mg to about 500 mg of DHA. In some embodiments, the composition comprises about 50 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, or about 500 mg of DHA. In some embodiments, the composition comprises at least about 50 mg, at least about 110 mg, at least about 120 mg, at least about 130 mg, at least about 140 mg, at least about 150 mg, at least about 200 mg, at least about 250 mg, at least about 300 mg, at least about 350 mg, at least about 400 mg, or at least about 500 mg of DHA. In some embodiments, the composition comprises up to about 50 mg, up to about 110 mg, up to about 120 mg, up to about 130 mg, up to about 140 mg, up to about 150 mg, up to about 200 mg, up to about 250 mg, up to about 300 mg, up to about 350 mg, up to about 400 mg, or up to about 500 mg of DHA.

[0075] In some embodiments, the composition is formulated as a semi-solid. In some embodiments, the composition is formulated as a soft gel capsule. In some embodiments, the composition is formulated as a solid dispersion. In some embodiments, the composition is formulated for oral delivery of retinoids. In some embodiments, the composition is formulated as eye drops. In some embodiments, the composition is formulated for topical or transdermal delivery of retinoids. In some embodiments, the composition containing retinoids can be formulated for topical application to the eye or for systemic application, such as intravenous, intramuscular, subcutaneous, enteral, parenteral, or oral administration. In some embodiments, the composition can be formulated with another ophthalmological agent, such as an isotonic agent, buffer, surfactant, or preservative. In some embodiments, the pH of the composition is within an acceptable range for ophthalmologic formulation, such as about pH 4 to pH 8. In some embodiments, the composition is formulated for slow or timed release of retinoids. For example, compositions can be formulated for delayed or sustained release of retinoids to deliver retinoids over a course of one or more dosing periods. Such compositions can reduce or eliminate the need for repeated administration.

[0076] In some embodiments, the compositions described herein can be formulated for the delivery of retinoids to a subject. Example 1 illustrates a non-limiting example of the manufacture of the composition. In some embodiments, the compositions described herein can be formulated as oil-based capsules, wherein the retinoids are soluble in a carrier oil. Non-limiting examples of carrier oils include soybean oil, sunflower oil, safflower oil, or fish oil. The choice of carrier oil can adjust the stability, bioavailability, or shelf life of the retinoids. In some embodiments, the retinoids can be mixed with the carrier oil. In some embodiments, the mixture can then be encapsulated in a soft gel capsule shell made of gelatin or other suitable material. In some embodiments, the composition may also include additional excipients for increasing water solubility or retinoid bioavailability. For example, hydroxypropyl-β-cyclodextrin (HPBCD) or nanoparticles (e.g., lipid nanoparticles, nanomicelles, nanocapsules, or nanospheres) can be added to the composition. The inclusion of HPBCD can increase the water solubility of the retinoids. In some embodiments, the composition may also be formulated as a polymer or dispersion, wherein the composition comprises a combination of hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, polyvinylpyrrolidone-vinyl acetate, hydroxypropyl methylcellulose-acetic acid-succinate, or any mixture thereof. In some embodiments, the polymer or dispersion may be further processed by rapid evaporation, spray drying, precipitation, or melt extrusion to obtain an amorphous composition. In some embodiments, the compositions described herein may also be formulated as liquid capsules, oil-in-water emulsions, or lipid matrices. In some embodiments, the composition may be formulated as a solid dispersion. For example, retinoids may be incorporated into poly(lactic-co-glycolic acid) (PLGA) millimeter cylindrical implants.

[0077] In some embodiments, the composition is formulated for non-medical use. In some embodiments, the composition does not treat a disease or condition. For example, the composition may be used for aesthetic or cosmetic purposes. In some embodiments, the composition is a supplement.

[0078] In some embodiments, the composition comprises at least one additional ingredient. In some embodiments, the at least one additional ingredient includes an antioxidant. Non-limiting examples of antioxidants include vitamin C, vitamin E, zinc, grape seed extract, or combinations thereof. In some embodiments, the at least one additional ingredient includes a fatty acid, such as omega-3 fatty acids. In some embodiments, the at least one additional ingredient includes a carotenoid. Non-limiting examples of carotenoids include lutein, zeaxanthin, astaxanthin, or combinations thereof. In some embodiments, the at least one additional ingredient includes a flavonoid, such as anthocyanins. In some embodiments, the at least one additional ingredient includes an amino acid, such as taurine. In some embodiments, the composition comprises at least one additional ingredient, which includes an antioxidant, fatty acid, carotenoid, flavonoid, amino acid, or a combination thereof. In some embodiments, the composition comprises at least one additional ingredient, which includes two or more of an antioxidant, fatty acid, carotenoid, flavonoid, and amino acid. In some embodiments, the composition comprises at least one additional ingredient, which includes an antioxidant, fatty acid, carotenoid, flavonoid, and amino acid.

[0079] In some embodiments, the composition comprises at least one additional ingredient, which includes a curcumin compound. In some embodiments, the curcumin compound includes curcuminoids. In some embodiments, the composition comprises about 10 mg to about 500 mg of curcuminoids. In some embodiments, the composition comprises about 10 mg to about 110 mg, about 10 mg to about 20 mg, about 10 mg to about 30 mg, about 10 mg to about 50 mg, about 10 mg to about 100 mg, about 10 mg to about 150 mg, about 10 mg to about 200 mg, about 10 mg to about 250 mg, about 10 mg to about 300 mg, about 10 mg to about 400 mg, or about 10 mg to about 500 mg of curcuminoids. In some embodiments, the composition comprises about 20 mg to about 30 mg, about 20 mg to about 50 mg, about 20 mg to about 100 mg, about 20 mg to about 150 mg, about 20 mg to about 200 mg, about 20 mg to about 250 mg, about 20 mg to about 300 mg, about 20 mg to about 400 mg, or about 20 mg to about 500 mg of curcuminoids. In some embodiments, the composition comprises about 30 mg to about 50 mg, about 30 mg to about 100 mg, about 30 mg to about 150 mg, about 30 mg to about 200 mg, about 30 mg to about 250 mg, about 30 mg to about 300 mg, about 30 mg to about 400 mg, or about 30 mg to about 500 mg of curcuminoids. In some embodiments, the composition comprises about 50 mg to about 100 mg, about 50 mg to about 150 mg, about 50 mg to about 200 mg, about 50 mg to about 250 mg, about 50 mg to about 300 mg, about 50 mg to about 400 mg, or about 50 mg to about 500 mg of curcuminoids. In some embodiments, the composition comprises about 100 mg to about 150 mg, about 100 mg to about 200 mg, about 100 mg to about 250 mg, about 100 mg to about 300 mg, about 100 mg to about 400 mg, or about 100 mg to about 500 mg of curcuminoids. In some embodiments, the composition comprises about 150 mg to about 200 mg, about 150 mg to about 250 mg, about 150 mg to about 300 mg, about 150 mg to about 400 mg, or about 150 mg to about 500 mg of curcuminoids. In some embodiments, the composition comprises about 200 mg to about 250 mg, about 200 mg to about 300 mg, about 200 mg to about 400 mg, or about 200 mg to about 500 mg of curcuminoids.In some embodiments, the composition comprises about 250 mg to about 300 mg, about 250 mg to about 400 mg, about 250 mg to about 500 mg, about 300 mg to about 400 mg, or about 300 mg to about 500 mg of curcuminoids. In some embodiments, the composition comprises about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, or about 500 mg of curcuminoids. In some embodiments, the composition comprises at least about 10 mg, at least about 20 mg, at least about 30 mg, at least about 40 mg, at least about 50 mg, at least about 100 mg, at least about 150 mg, at least about 200 mg, at least about 250 mg, at least about 300 mg, at least about 400 mg, or at least about 500 mg of curcuminoids. In some embodiments, the composition comprises up to about 10 mg, up to about 20 mg, up to about 30 mg, up to about 400 mg, up to about 50 mg, up to about 100 mg, up to about 150 mg, up to about 200 mg, up to about 250 mg, up to about 300 mg, up to about 400 mg, or up to about 500 mg of curcuminoids.

[0080] In some embodiments, the composition comprises at least one additional ingredient, which includes a carotenoid. In some embodiments, the carotenoid includes lutein, zeaxanthin, or astaxanthin. In some embodiments, the composition comprises about 0.5 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 0.5 mg to about 1 mg, about 0.5 mg to about 2 mg, about 0.5 mg to about 5 mg, about 0.5 mg to about 10 mg, about 0.5 mg to about 20 mg, about 0.5 mg to about 30 mg, about 0.5 mg to about 40 mg, or about 0.5 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 1 mg to about 2 mg, about 1 mg to about 5 mg, about 1 mg to about 10 mg, about 1 mg to about 20 mg, about 1 mg to about 30 mg, about 1 mg to about 40 mg, or about 1 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 2 mg to about 5 mg, about 2 mg to about 10 mg, about 2 mg to about 20 mg, about 2 mg to about 30 mg, about 2 mg to about 40 mg, or about 2 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 5 mg to about 10 mg, about 5 mg to about 20 mg, about 5 mg to about 30 mg, about 5 mg to about 40 mg, or about 5 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 10 mg to about 20 mg, about 10 mg to about 30 mg, about 10 mg to about 40 mg, or about 10 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 20 mg to about 30 mg, about 20 mg to about 40 mg, or about 20 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 30 mg to about 40 mg, or about 30 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 40 mg to about 50 mg of lutein. In some embodiments, the composition comprises about 0.5 mg, about 1 mg, about 2 mg, about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, or about 50 mg of lutein. In some embodiments, the composition comprises at least about 0.5 mg, at least about 1 mg, at least about 2 mg, at least about 5 mg, at least about 10 mg, at least about 20 mg, at least about 30 mg, at least about 40 mg, or at least about 50 mg of lutein. In some embodiments, the composition comprises at most about 1 mg, at most about 2 mg, at most about 5 mg, at most about 10 mg, at most about 20 mg, at most about 30 mg, at most about 40 mg, or at most about 50 mg of lutein.

[0081] In some embodiments, the composition comprises about 0.5 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 0.5 mg to about 1 mg, about 0.5 mg to about 2 mg, about 0.5 mg to about 5 mg, about 0.5 mg to about 10 mg, about 0.5 mg to about 20 mg, about 0.5 mg to about 30 mg, about 0.5 mg to about 40 mg, or about 0.5 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 1 mg to about 2 mg, about 1 mg to about 5 mg, about 1 mg to about 10 mg, about 1 mg to about 20 mg, about 1 mg to about 30 mg, about 1 mg to about 40 mg, or about 1 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 2 mg to about 5 mg, about 2 mg to about 10 mg, about 2 mg to about 20 mg, about 2 mg to about 30 mg, about 2 mg to about 40 mg, or about 2 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 5 mg to about 10 mg, about 5 mg to about 20 mg, about 5 mg to about 30 mg, about 5 mg to about 40 mg, or about 5 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 10 mg to about 20 mg, about 10 mg to about 30 mg, about 10 mg to about 40 mg, or about 10 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 20 mg to about 30 mg, about 20 mg to about 40 mg, or about 20 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 30 mg to about 40 mg, or about 30 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 40 mg to about 50 mg of zeaxanthin. In some embodiments, the composition comprises about 0.5 mg, about 1 mg, about 2 mg, about 5 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, or about 50 mg of zeaxanthin. In some embodiments, the composition comprises at least about 0.5 mg, at least about 1 mg, at least about 2 mg, at least about 5 mg, at least about 10 mg, at least about 20 mg, at least about 30 mg, at least about 40 mg, or at least about 50 mg of zeaxanthin. In some embodiments, the composition comprises at most about 1 mg, at most about 2 mg, at most about 5 mg, at most about 10 mg, at most about 20 mg, at most about 30 mg, at most about 40 mg, or at most about 50 mg of zeaxanthin.

[0082] In some embodiments, the composition comprises a surfactant. Non-limiting examples of surfactants may include Tween, Kolliphor, Labrasol, Gelucire, Capmul, polyethylene glycol (PEG), Transcutol, Capryol, or combinations thereof. In some embodiments, the composition comprises a surfactant including Gelucire (e.g., Gelucire 44 / 14). In some embodiments, the composition comprises about 0.01 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 0.01 mL to about 0.05 mL, about 0.01 mL to about 0.1 mL, about 0.01 mL to about 0.5 mL, about 0.01 mL to about 1 mL, about 0.01 mL to about 2 mL, about 0.01 mL to about 3 mL, about 0.01 mL to about 4 mL, or about 0.01 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 0.05 mL to about 0.1 mL, about 0.05 mL to about 0.5 mL, about 0.05 mL to about 1 mL, about 0.05 mL to about 2 mL, about 0.05 mL to about 3 mL, about 0.05 mL to about 4 mL, or about 0.05 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 0.1 mL to about 0.5 mL, about 0.1 mL to about 1 mL, about 0.1 mL to about 2 mL, about 0.1 mL to about 3 mL, about 0.1 mL to about 4 mL, or about 0.1 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 0.5 mL to about 1 mL, about 0.5 mL to about 2 mL, about 0.5 mL to about 3 mL, about 0.5 mL to about 4 mL, or about 0.5 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 1 mL to about 2 mL, about 1 mL to about 3 mL, about 1 mL to about 4 mL, or about 1 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 2 mL to about 3 mL, about 2 mL to about 4 mL, or about 2 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 3 mL to about 4 mL or about 3 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 4 mL to about 5 mL of Gelucire. In some embodiments, the composition comprises about 0.01 mL, about 0.05 mL, about 0.1 mL, about 0.5 mL, about 1 mL, about 2 mL, about 3 mL, about 4 mL, or about 5 mL of Gelucire.In some embodiments, the composition comprises at least about 0.01 mL, at least about 0.05 mL, at least about 0.1 mL, at least about 0.5 mL, at least about 1 mL, at least about 2 mL, at least about 3 mL, at least about 4 mL, or at least about 5 mL of Gelucire. In some embodiments, the composition comprises up to about 0.05 mL, up to about 0.1 mL, up to about 0.5 mL, up to about 1 mL, up to about 2 mL, up to about 3 mL, up to about 4 mL, or up to about 5 mL of Gelucire.

[0083] In some embodiments, the composition comprises a surfactant, including Capmul (e.g., Capmul MCM). In some embodiments, the composition comprises about 0.01 mL to about 5 mL of Capmul. In some embodiments, the composition comprises about 0.01 mL to about 0.05 mL, about 0.01 mL to about 0.1 mL, about 0.01 mL to about 0.5 mL, about 0.01 mL to about 1 mL, about 0.01 mL to about 2 mL, about 0.01 mL to about 3 mL, about 0.01 mL to about 4 mL, or about 0.01 mL to about 5 mL of Capmul. In some embodiments, the composition comprises about 0.05 mL to about 0.1 mL, about 0.05 mL to about 0.5 mL, about 0.05 mL to about 1 mL, about 0.05 mL to about 2 mL, about 0.05 mL to about 3 mL, about 0.05 mL to about 4 mL, or about 0.05 mL to about 5 mL of Capmul. In some embodiments, the composition comprises about 0.1 mL to about 0.5 mL, about 0.1 mL to about 1 mL, about 0.1 mL to about 2 mL, about 0.1 mL to about 3 mL, about 0.1 mL to about 4 mL, or about 0.1 mL to about 5 mL of capmul. In some embodiments, the composition comprises about 0.5 mL to about 1 mL, about 0.5 mL to about 2 mL, about 0.5 mL to about 3 mL, about 0.5 mL to about 4 mL, or about 0.5 mL to about 5 mL of capmul. In some embodiments, the composition comprises about 1 mL to about 2 mL, about 1 mL to about 3 mL, about 1 mL to about 4 mL, or about 1 mL to about 5 mL of capmul. In some embodiments, the composition comprises about 2 mL to about 3 mL, about 2 mL to about 4 mL, or about 2 mL to about 5 mL of capmul. In some embodiments, the composition comprises about 3 mL to about 4 mL or about 3 mL to about 5 mL of capmul. In some embodiments, the composition comprises about 4 mL to about 5 mL of capmul. In some embodiments, the composition comprises about 0.01 mL, about 0.05 mL, about 0.1 mL, about 0.5 mL, about 1 mL, about 2 mL, about 3 mL, about 4 mL, or about 5 mL of capmul. In some embodiments, the composition comprises at least about 0.01 mL, at least about 0.05 mL, at least about 0.1 mL, at least about 0.5 mL, at least about 1 mL, at least about 2 mL, at least about 3 mL, at least about 4 mL, or at least about 5 mL of capmul.In some embodiments, the composition comprises up to about 0.05 mL, up to about 0.1 mL, up to about 0.5 mL, up to about 1 mL, up to about 2 mL, up to about 3 mL, up to about 4 mL, or up to about 5 mL of capmul.

[0084] In some embodiments, the composition comprises a surfactant, including Tween (e.g., Tween 80). In some embodiments, the composition comprises about 0.01 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 0.01 mL to about 0.05 mL, about 0.01 mL to about 0.1 mL, about 0.01 mL to about 0.3 mL, about 0.01 mL to about 0.5 mL, about 0.01 mL to about 1 mL, about 0.01 mL to about 2 mL, about 0.01 mL to about 3 mL, about 0.01 mL to about 4 mL, or about 0.01 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 0.05 mL to about 0.1 mL, about 0.05 mL to about 0.3 mL, about 0.05 mL to about 0.5 mL, about 0.05 mL to about 1 mL, about 0.05 mL to about 2 mL, about 0.05 mL to about 3 mL, about 0.05 mL to about 4 mL, or about 0.05 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 0.1 mL to about 0.3 mL, about 0.1 mL to about 0.5 mL, about 0.1 mL to about 1 mL, about 0.1 mL to about 2 mL, about 0.1 mL to about 3 mL, about 0.1 mL to about 4 mL, or about 0.1 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 0.3 mL to about 0.5 mL, about 0.3 mL to about 1 mL, about 0.3 mL to about 2 mL, about 0.3 mL to about 3 mL, about 0.3 mL to about 4 mL, or about 0.3 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 1 mL to about 2 mL, about 1 mL to about 3 mL, about 1 mL to about 4 mL, or about 1 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 2 mL to about 3 mL, about 2 mL to about 4 mL, or about 2 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 3 mL to about 4 mL or about 3 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 4 mL to about 5 mL of Tween. In some embodiments, the composition comprises about 0.01 mL, about 0.05 mL, about 0.1 mL, about 0.3 mL, about 0.5 mL, about 1 mL, about 2 mL, about 3 mL, about 4 mL, or about 5 mL of Tween.In some embodiments, the composition comprises at least about 0.01 mL, at least about 0.05 mL, at least about 0.1 mL, at least about 0.3 mL, at least about 0.5 mL, at least about 1 mL, at least about 2 mL, at least about 3 mL, at least about 4 mL, or at least about 5 mL of Tween. In some embodiments, the composition comprises up to about 0.05 mL, up to about 0.1 mL, up to about 0.3 mL, up to about 0.5 mL, up to about 1 mL, up to about 2 mL, up to about 3 mL, up to about 4 mL, or up to about 5 mL of Tween.

[0085] In some embodiments, the composition comprises a surfactant, including PEG (e.g., PEG400). In some embodiments, the composition comprises about 0.01 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 0.01 mL to about 0.05 mL, about 0.01 mL to about 0.1 mL, about 0.01 mL to about 0.3 mL, about 0.01 mL to about 0.5 mL, about 0.01 mL to about 1 mL, about 0.01 mL to about 2 mL, about 0.01 mL to about 3 mL, about 0.01 mL to about 4 mL, or about 0.01 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 0.05 mL to about 0.1 mL, about 0.05 mL to about 0.3 mL, about 0.05 mL to about 0.5 mL, about 0.05 mL to about 1 mL, about 0.05 mL to about 2 mL, about 0.05 mL to about 3 mL, about 0.05 mL to about 4 mL, or about 0.05 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 0.1 mL to about 0.3 mL, about 0.1 mL to about 0.5 mL, about 0.1 mL to about 1 mL, about 0.1 mL to about 2 mL, about 0.1 mL to about 3 mL, about 0.1 mL to about 4 mL, or about 0.1 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 0.3 mL to about 0.5 mL, about 0.3 mL to about 1 mL, about 0.3 mL to about 2 mL, about 0.3 mL to about 3 mL, about 0.3 mL to about 4 mL, or about 0.3 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 1 mL to about 2 mL, about 1 mL to about 3 mL, about 1 mL to about 4 mL, or about 1 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 2 mL to about 3 mL, about 2 mL to about 4 mL, or about 2 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 3 mL to about 4 mL, or about 3 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 4 mL to about 5 mL of PEG. In some embodiments, the composition comprises about 0.01 mL, about 0.05 mL, about 0.1 mL, about 0.3 mL, about 0.5 mL, about 1 mL, about 2 mL, about 3 mL, about 4 mL, or about 5 mL of PEG.In some embodiments, the composition comprises at least about 0.01 mL, at least about 0.05 mL, at least about 0.1 mL, at least about 0.3 mL, at least about 0.5 mL, at least about 1 mL, at least about 2 mL, at least about 3 mL, at least about 4 mL, or at least about 5 mL of PEG. In some embodiments, the composition comprises up to about 0.05 mL, up to about 0.1 mL, up to about 0.3 mL, up to about 0.5 mL, up to about 1 mL, up to about 2 mL, up to about 3 mL, up to about 4 mL, or up to about 5 mL of PEG.

[0086] In some embodiments, the composition comprises a surfactant, including Kolliphor (e.g., Kolliphor EL). In some embodiments, the composition comprises about 0.01 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 0.01 mL to about 0.05 mL, about 0.01 mL to about 0.1 mL, about 0.01 mL to about 0.3 mL, about 0.01 mL to about 0.5 mL, about 0.01 mL to about 1 mL, about 0.01 mL to about 2 mL, about 0.01 mL to about 3 mL, about 0.01 mL to about 4 mL, or about 0.01 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 0.05 mL to about 0.1 mL, about 0.05 mL to about 0.3 mL, about 0.05 mL to about 0.5 mL, about 0.05 mL to about 1 mL, about 0.05 mL to about 2 mL, about 0.05 mL to about 3 mL, about 0.05 mL to about 4 mL, or about 0.05 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 0.1 mL to about 0.3 mL, about 0.1 mL to about 0.5 mL, about 0.1 mL to about 1 mL, about 0.1 mL to about 2 mL, about 0.1 mL to about 3 mL, about 0.1 mL to about 4 mL, or about 0.1 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 0.3 mL to about 0.5 mL, about 0.3 mL to about 1 mL, about 0.3 mL to about 2 mL, about 0.3 mL to about 3 mL, about 0.3 mL to about 4 mL, or about 0.3 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 0.5 mL to about 1 mL, about 0.5 mL to about 2 mL, about 0.5 mL to about 3 mL, about 0.5 mL to about 4 mL, or about 0.5 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 1 mL to about 2 mL, about 1 mL to about 3 mL, about 1 mL to about 4 mL, or about 1 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 2 mL to about 3 mL, about 2 mL to about 4 mL, or about 2 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 3 mL to about 4 mL or about 3 mL to about 5 mL of Kolliphor. In some embodiments, the composition comprises about 4 mL to about 5 mL of Kolliphor.In some embodiments, the composition comprises about 0.01 mL, about 0.05 mL, about 0.1 mL, about 0.3 mL, about 0.5 mL, about 1 mL, about 2 mL, about 3 mL, about 4 mL, or about 5 mL of Kolliphor. In some embodiments, the composition comprises at least about 0.01 mL, at least about 0.05 mL, at least about 0.1 mL, at least about 0.3 mL, at least about 0.5 mL, at least about 1 mL, at least about 2 mL, at least about 3 mL, at least about 4 mL, or at least about 5 mL of Kolliphor. In some embodiments, the composition comprises at most about 0.05 mL, at most about 0.1 mL, at most about 0.3 mL, at most about 0.5 mL, at most about 1 mL, at most about 2 mL, at most about 3 mL, at most about 4 mL, or at most about 5 mL of Kolliphor.

[0087] In some embodiments, the composition comprises a surfactant, including Transcutol (e.g., Transcutol HP). In some embodiments, the composition comprises about 0.01 mL to about 5 mL of Transcutol. In some embodiments, the composition comprises about 0.01 mL to about 0.05 mL, about 0.01 mL to about 0.1 mL, about 0.01 mL to about 0.3 mL, about 0.01 mL to about 0.5 mL, about 0.01 mL to about 1 mL, about 0.01 mL to about 2 mL, about 0.01 mL to about 3 mL, about 0.01 mL to about 4 mL, or about 0.01 mL to about 5 mL of Transcutol. In some embodiments, the composition comprises about 0.05 mL to about 0.1 mL, about 0.05 mL to about 0.3 mL, about 0.05 mL to about 0.5 mL, about 0.05 mL to about 1 mL, about 0.05 mL to about 2 mL, about 0.05 mL to about 3 mL, about 0.5 mL to about 4 mL, or about 0.05 mL to about 5 mL of Transcutol. In some embodiments, the composition comprises about 0.1 mL to about 0.3 mL, about 0.1 mL to about 0.5 mL, about 0.1 mL to about 1 mL, about 0.1 mL to about 2 mL, about 0.1 mL to about 3 mL, about 0.1 mL to about 4 mL, or about 0.1 mL to about 5 mL of Transcutol. In some embodiments, the composition comprises about 0.3 mL to about 0.5 mL, about 0.3 mL to about 1 mL, about 0.3 mL to about 2 mL, about 0.3 mL to about 3 mL, about 0.3 mL to about 4 mL, or about 0.3 mL to about 5 mL of Transcutol. In some embodiments, the composition comprises about 1 mL to about 2 mL, about 1 mL to about 3 mL, about 1 mL to about 4 mL, or about 1 mL to about 5 mL of Transcutol. In some embodiments, the composition comprises about 2 mL to about 3 mL, about 2 mL to about 4 mL, or about 2 mL to about 5 mL of Transcutol. In some embodiments, the composition comprises about 3 mL to about 4 mL, or about 3 mL or about 5 mL of Transcutol. In some embodiments, the composition comprises about 4 mL to about 5 mL of Transcutol.In some embodiments, the composition comprises about 0.01 mL, about 0.05 mL, about 0.1 mL, about 0.3 mL, about 0.5 mL, about 1 mL, about 2 mL, about 3 mL, about 4 mL, or about 5 mL of Transcutol. In some embodiments, the composition comprises at least about 0.01 mL, at least about 0.05 mL, at least about 0.1 mL, at least about 0.3 mL, at least about 0.5 mL, at least about 1 mL, at least about 2 mL, at least about 3 mL, at least about 4 mL, or at least about 5 mL of Transcutol. In some embodiments, the composition comprises at most about 0.05 mL, at most about 0.1 mL, at most about 0.3 mL, at most about 0.5 mL, at most about 1 mL, at most about 2 mL, at most about 3 mL, at most about 4 mL, or at most about 5 mL of Transcutol.

[0088] In some embodiments, the composition is formulated for ocular application to a subject. In some embodiments, the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in the subject. In some embodiments, the composition modulates gene expression in retinal pigment epithelial (RPE) cells. In some embodiments, the composition increases the bioavailability of retinoids delivered to RPE cells compared to the second bioavailability of retinoids delivered to RPE cells without lipid excipients or surfactants. In some embodiments, the bioavailability is increased by at least about 5% to about 5,000%. In some embodiments, bioavailability is increased by at least about 5% to about 10%, about 5% to about 20%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 5% to about 100%, about 5% to about 200%, about 5% to about 500%, about 5% to about 1,000%, about 5% to about 5,000%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, and about 10% to Approximately 100%, approximately 10% to approximately 200%, approximately 10% to approximately 500%, approximately 10% to approximately 1,000%, approximately 10% to approximately 5,000%, approximately 20% to approximately 30%, approximately 20% to approximately 40%, approximately 20% to approximately 50%, approximately 20% to approximately 100%, approximately 20% to approximately 200%, approximately 20% to approximately 500%, approximately 20% to approximately 1,000%, approximately 20% to approximately 5,000%, approximately 30% to approximately 40%, approximately 30% to approximately 50%. Approximately 30% to approximately 100%, approximately 30% to approximately 200%, approximately 30% to approximately 500%, approximately 30% to approximately 1,000%, approximately 30% to approximately 5,000%, approximately 40% to approximately 50%, approximately 40% to approximately 100%, approximately 40% to approximately 200%, approximately 40% to approximately 500%, approximately 40% to approximately 1,000%, approximately 40% to approximately 5,000%, approximately 50% to approximately 100%, approximately 50% to approximately 200%, approximately 50% to approximately 500%. About 50% to about 1,000%, about 50% to about 5,000%, about 100% to about 200%, about 100% to about 500%, about 100% to about 1,000%, about 100% to about 5,000%, about 200% to about 500%, about 200% to about 1,000%, about 200% to about 5,000%, about 500% to about 1,000%, about 500% to about 5,000%, or about 1,000% to about 5,000%. In some embodiments, bioavailability is increased by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 100%, about 200%, about 500%, about 1,000%, or about 5,000%.In some embodiments, bioavailability is increased by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 100%, about 200%, about 500%, or about 1,000%. In some embodiments, bioavailability is increased by at least, and at most, about 10%, about 20%, about 30%, about 40%, about 50%, about 100%, about 200%, about 500%, about 1,000%, or about 5,000% compared to the second bioavailability of delivering retinoids to RPE cells without lipid excipients or surfactants.

[0089] In some embodiments, the composition increases the stability of retinoids compared to the second stability of retinoids in comparable compositions that do not contain lipid excipients or surfactants. In some embodiments, the stability is increased by at least about 5% to about 5,000% compared to the second stability of retinoids in comparable compositions that do not contain lipid excipients or surfactants. In some embodiments, the stability is increased by at least about 5% to about 10%, about 5% to about 20%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 5% to about 100%, about 5% to about 200%, about 5% to about 500%, about 5% to about 1,000%, about 5% to about 5,000%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about 50%, and so on. 100%, about 10% to about 200%, about 10% to about 500%, about 10% to about 1,000%, about 10% to about 5,000%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 100%, about 20% to about 200%, about 20% to about 500%, about 20% to about 1,000%, about 20% to about 5,000%, about 30% to about 40%, about 30% to about 50%. Approximately 30% to approximately 100%, approximately 30% to approximately 200%, approximately 30% to approximately 500%, approximately 30% to approximately 1,000%, approximately 30% to approximately 5,000%, approximately 40% to approximately 50%, approximately 40% to approximately 100%, approximately 40% to approximately 200%, approximately 40% to approximately 500%, approximately 40% to approximately 1,000%, approximately 40% to approximately 5,000%, approximately 50% to approximately 100%, approximately 50% to approximately 200%, approximately 50% to approximately 500%. Approximately 50% to approximately 1,000%, approximately 50% to approximately 5,000%, approximately 100% to approximately 200%, approximately 100% to approximately 500%, approximately 100% to approximately 1,000%, approximately 100% to approximately 5,000%, approximately 200% to approximately 500%, approximately 200% to approximately 1,000%, approximately 200% to approximately 5,000%, approximately 500% to approximately 1,000%, approximately 500% to approximately 5,000%, or approximately 1,000% to approximately 5,000%. In some embodiments, stability is increased by at least approximately 5%, approximately 10%, approximately 20%, approximately 30%, approximately 40%, approximately 50%, approximately 100%, approximately 200%, approximately 500%, approximately 1,000%, or approximately 5,000%. In some implementations, stability is increased by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 100%, about 200%, about 500%, or about 1,000%.In some embodiments, the stability is increased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 100%, about 200%, about 500%, about 1,000%, or about 5,000% compared to the second stability of retinoids in comparable compositions that do not contain lipid excipients or surfactants.

[0090] In some embodiments, the composition increases the solubility of retinoids compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the solubility increases by at least about 5% to about 5,000% compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the solubility increases by at least about 5% to about 10%, about 5% to about 20%, about 5% to about 30%, about 5% to about 40%, about 5% to about 50%, about 5% to about 100%, about 5% to about 200%, about 5% to about 500%, about 5% to about 1,000%, about 5% to about 5,000%, about 10% to about 20%, about 10% to about 30%, about 10% to about 40%, about 10% to about 50%, about 10% to about... 100%, about 10% to about 200%, about 10% to about 500%, about 10% to about 1,000%, about 10% to about 5,000%, about 20% to about 30%, about 20% to about 40%, about 20% to about 50%, about 20% to about 100%, about 20% to about 200%, about 20% to about 500%, about 20% to about 1,000%, about 20% to about 5,000%, about 30% to about 40%, about 30% to about 50%. Approximately 30% to approximately 100%, approximately 30% to approximately 200%, approximately 30% to approximately 500%, approximately 30% to approximately 1,000%, approximately 30% to approximately 5,000%, approximately 40% to approximately 50%, approximately 40% to approximately 100%, approximately 40% to approximately 200%, approximately 40% to approximately 500%, approximately 40% to approximately 1,000%, approximately 40% to approximately 5,000%, approximately 50% to approximately 100%, approximately 50% to approximately 200%, approximately 50% to approximately 500%. About 50% to about 1,000%, about 50% to about 5,000%, about 100% to about 200%, about 100% to about 500%, about 100% to about 1,000%, about 100% to about 5,000%, about 200% to about 500%, about 200% to about 1,000%, about 200% to about 5,000%, about 500% to about 1,000%, about 500% to about 5,000%, or about 1,000% to about 5,000%. In some embodiments, the solubility increases by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 100%, about 200%, about 500%, about 1,000%, or about 5,000%. In some implementations, the solubility increases by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 100%, about 200%, about 500%, about 1,000%, or about 5,000%.In some embodiments, the solubility is increased by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 100%, about 200%, about 500%, about 1,000%, or about 5,000% compared to the second solubility of retinoids in a comparable composition that does not contain lipid excipients or surfactants.

[0091] In some embodiments, the composition increases the bioavailability of retinoids in a subject compared to the second bioavailability of retinoids in a comparable composition that does not contain lipid excipients or surfactants. In some embodiments, the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability in a subject. In some embodiments, the composition does not decrease the bioavailability of retinoids in a subject compared to the second bioavailability of retinoids in a comparable composition that does not contain lipid excipients or surfactants. In some embodiments, bioavailability and second bioavailability are determined by the plasma concentration of retinoids obtained from the subject. Figure 9 The figure illustrates that the bioavailability of retinol formulated in the non-limiting examples of the compositions described herein is not reduced compared to other comparable formulations.

[0092] method In some aspects, this document describes a method for treating a disease or condition in a subject by administering the composition described herein to the subject. In some embodiments, the disease or condition is associated with retinoic acid deficiency in the subject. In some embodiments, a composition comprising both retinoids and a lipid excipient increases the bioavailability of retinoids in the subject compared to the second bioavailability of retinoids formulated with an excipient different from a lipid excipient. In some embodiments, a composition comprising both retinoids and a lipid excipient increases the bioavailability of retinoids in the subject by at least 10%, at least 20%, at least 50%, at least 100%, or more. In some embodiments, the increased bioavailability of retinoids in the subject increases the therapeutic efficacy for treating the disease or condition. In some embodiments, the increased bioavailability of retinoids in the subject reduces the dose of retinoid required to achieve equivalent therapeutic efficacy in the subject. In some embodiments, the method described herein reduces retinoid toxicity in the subject. Examples 2 and 3 illustrate studies examining the safety and therapeutic efficacy of the compositions described herein.

[0093] In some embodiments, the method includes administering the composition described herein to a subject who suffers from an eye disease or eye condition. In some embodiments, the eye disease or eye condition is associated with the accumulation of lipofuscin. In some embodiments, the method reduces the accumulation of vitamin A dimer in the subject. In some embodiments, the method reduces the accumulation of lipofuscin in the subject. In some embodiments, the eye disease or eye condition is associated with retinal pigment epithelial (RPE) cells. In some embodiments, the eye disease or eye condition is associated with the accumulation of lipofuscin in RPE cells. In some embodiments, the eye disease or eye condition is associated with the accumulation of A2E. In some embodiments, the eye disease or eye condition is associated with the accumulation of A2E in RPE cells. In some embodiments, the method reduces the accumulation of A2E in the subject. In some embodiments, the eye disease or eye condition is associated with RPE cells. In some embodiments, the eye disease or eye condition is macular degeneration. Non-limiting examples of macular degeneration include age-related macular degeneration (AMD), vitrectomycosis, bull's-eye macular degeneration, central serous retinopathy, Charles-Bonnett syndrome (CBS), cone dystrophy, Doyne's cellulopathy, diabetic macular edema (DMO), macular hole, macular edema, myopic macular degeneration, pattern dystrophy, pseudoxanthoma elastica (PXE), punctate intrachorioretinopathy (PIC), retinal vein occlusion (RVO), Sotheby's dystrophy, Staggart's disease, or combinations thereof. In some embodiments, the ocular disease or condition is dry AMD. In some embodiments, the ocular disease or condition is early AMD. In some embodiments, the ocular disease or condition is wet AMD.

[0094] In some implementations, the efficacy of a treatment for an eye disease or condition can be determined by visual function (e.g., Example 3). In some implementations, improvements in visual function in one or both eyes of a subject can be evaluated based on measurements of visual field, visual acuity and retinal sensitivity tests, electroretinogram, dynamic pupillary response, nystagmus, cortical visual function, color vision, visual mobility tests, patient-reported quality of life / ability to perform daily tasks, or combinations thereof. Improvements in visual function in one or both eyes of a subject during a treatment regimen can be demonstrated by comparing the visual function of each eye of the subject to baseline measurements of visual function in each eye of the subject prior to treatment with the treatment regimen, or by comparing the visual function of each eye of the subject to a comparable untreated human visual system.

[0095] use In some aspects, this document describes methods of using the compositions described herein or uses of the compositions described herein. In some embodiments, the use is for non-medical or non-therapeutic purposes. Example 5 illustrates a non-limiting example of a non-medical or non-therapeutic use. In some embodiments, the use does not treat a disease or condition. For example, the use may be for aesthetic or cosmetic purposes. In some embodiments, the use is for aesthetic purposes. In some embodiments, the use is for cosmetic purposes. In some embodiments, the use is for supplementary purposes. In some embodiments, the composition formulated for non-medical or non-therapeutic purposes comprises retinoids; lipid excipients; or surfactants. In some embodiments, the lipid excipient increases the bioavailability of retinoids in a subject by at least 10% compared to the second bioavailability of retinoids formulated with excipients different from lipid excipients. In some embodiments, the retinoids comprise the structure of Formula I: In some embodiments, each of the numerals 1 to 20 represents a position of a carbon covalently bonded to at least one hydrogen atom, wherein the at least one hydrogen atom is substituted with at least one deuterium atom. In some embodiments, R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), or R5 (COO-glucuronide). In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at positions 10, 12, 14, 19, 20, or combinations thereof. In some embodiments, the carbon atom substituted with at least one hydrogen atom is located at position 19 or at position 20. In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at position 19 or position 20, said position 19 comprising three hydrogen atoms replacing three hydrogen atoms (19, 19, 19-trideuterated retinol), said position 20 comprising three hydrogen atoms replacing three hydrogen atoms (20, 20, 20-trideuterated retinol). Example 4 illustrates the potency study of the 20, 20, 20-trideuterated retinol described herein. In some embodiments, the carbon with at least one hydrogen atom replaced by at least one deuterium is located at positions 19 and 20, said position 19 comprising three hydrogen atoms replacing three hydrogen atoms, said position 20 comprising three hydrogen atoms replacing three hydrogen atoms. In some embodiments, 19, 19, 19-trideuterated retinol comprises 19, 19, 19-trideuterated retinol analogs. In some embodiments, the 19,19,19-trideuterated retinol analogues comprise 19,19,19-trideuterated retinol esters. In some embodiments, the 19,19,19-trideuterated retinol analogues comprise 19,19,19-trideuterated retinol acetate. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol analogues. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol esters. In some embodiments, the 20,20,20-trideuterated retinol analogues comprise 20,20,20-trideuterated retinol acetate. In some embodiments, the carbon atoms in which at least one hydrogen atom is replaced by at least one deuterium are located at positions 19 and 20, wherein position 19 comprises replacing three hydrogen atoms with three deuterium atoms, and position 20 comprises replacing three hydrogen atoms with three deuterium atoms (19, 19, 19, 20, 20, 20-hexadeuterated retinol). In some embodiments, 19, 19, 19, 20, 20, 20-hexadeuterated retinol comprises 19, 19, 19, 20, 20, 20-hexadeuterated retinol analogs.In some embodiments, the 19,19,19,20,20,20-hexadeuterated retinol analogues include 19,19,19,20,20,20-hexadeuterated retinol esters. In some embodiments, the 19,19,19,20,20,20-hexadeuterated retinol analogues include 19,19,19,20,20,20-hexadeuterated retinol acetate.

[0096] In some embodiments, the composition comprises from about 1.0 mg to about 5.0 mg of retinoids. In some embodiments, the lipid excipient comprises omega-3 fatty acids. In some embodiments, the omega-3 fatty acids include EPA or DHA. In some embodiments, the composition comprises from about 100 mg to about 500 mg of EPA. In some embodiments, the composition comprises from about 50 mg to about 200 mg of DHA. In some embodiments, the composition comprises at least one additional ingredient. In some embodiments, at least one additional ingredient includes an antioxidant, such as vitamin C, vitamin E, zinc, or grape seed extract. In some embodiments, at least one additional ingredient includes a curcumin compound. In some embodiments, at least one additional ingredient comprises from about 20 mg to about 100 mg of curcuminoids. In some embodiments, at least one additional ingredient includes a carotenoid, such as lutein, zeaxanthin, or astaxanthin. In some embodiments, the composition comprises from about 1 mg to about 100 mg of lutein. In some embodiments, the composition comprises from about 1 mg to about 10 mg of zeaxanthin. In some embodiments, at least one additional ingredient includes flavonoids, such as anthocyanins. In some embodiments, at least one additional ingredient includes amino acids or amino acid analogs. In some embodiments, at least one additional ingredient includes an emulsifier. In some embodiments, the surfactant includes Tween, Kolliphor, Labrasol, Gelucire, Capmul, PEG, Transcutol, Capryol, or combinations thereof. In some embodiments, the surfactant is composed of Gelucire, Capmul, Tween, and PEG.

[0097] In some embodiments, the composition is used in a semi-solid form. In some embodiments, the composition is formulated as a soft gel capsule. In some embodiments, the composition is formulated as a solid dispersion. In some embodiments, the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof. In some embodiments, the composition is formulated for ocular application to a subject. In some embodiments, the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in a subject. In some embodiments, the composition modulates gene expression in retinal pigment epithelial (RPE) cells. In some embodiments, the composition increases the bioavailability of retinoids delivered to RPE cells. As shown in Example 6, the compositions described herein can increase the bioavailability or stability of retinoids. In some embodiments, bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability of delivering retinoids to RPE cells without lipid excipients or surfactants. In some embodiments, the composition increases the stability of retinoids compared to the second stability of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the stability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second stability of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the composition increases the bioavailability of retinoids in a subject compared to the second bioavailability of retinoids in a comparable composition without lipid excipients or surfactants. In some embodiments, the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability in a subject. In some embodiments, the composition does not decrease the bioavailability of retinoids in a subject compared to the second bioavailability of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, bioavailability and second bioavailability are determined by the plasma concentration of retinoids obtained from the subject. In some embodiments, the composition increases the solubility of retinoids compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, the solubility increases by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second solubility of retinoids in comparable compositions without lipid excipients or surfactants. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 0.5% to about 90%. In some embodiments, retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%. In some embodiments, the composition comprises an oil.In some embodiments, the oil includes corn oil, oleic acid, Maisine cc, or combinations thereof. In some embodiments, the use described herein is for aesthetic purposes. In some embodiments, the use described herein is for cosmetic purposes. In some embodiments, the use described herein is for supplementary purposes. In some embodiments, the use described herein does not treat a disease or condition. In some embodiments, the use described herein involves topical or transdermal application of the composition to a subject.

[0098] The use of absolute or sequential terms, such as “will,” “will not,” “should,” “should not,” “must,” “must not,” “first,” “initially,” “next,” “following,” “before,” “after,” “finally,” and “end,” is not intended to limit the scope of the embodiments of the invention disclosed herein, but is illustrative.

[0099] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the,” as used herein, are intended to include the plural forms as well. Furthermore, with regard to the use of the terms “including,” “include,” “having,” “has,” “with,” or variations thereof in the detailed description and / or claims, such terms are intended to be inclusive in a manner similar to the term “comprising.”

[0100] As used herein, the terms “at least one,” “one or more,” and “and / or” are open-ended expressions that are both operationally connected and separate. For example, each of the expressions “at least one of A, B, and C,” “at least one of A, B, or C,” “one or more of A, B, and C,” “one or more of A, B, or C,” and “A, B, and / or C” means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B, and C together.

[0101] As used herein, "or" can mean "and," "or," or "and / or," and can be used exclusively and inclusively. For example, the term "A or B" can mean "A or B," "A but not B," "B but not A," and "A and B." In some cases, the context can indicate a specific meaning.

[0102] Any systems, methods, software, and platforms described herein are modular. Therefore, terms such as “first” and “second” do not necessarily imply priority, order of importance, or sequence of actions.

[0103] When the term "about" refers to a number or range of values, it means that the number or range is an approximation within experimental variability (or within statistical experimental error), and that the number or range may vary, for example, from 1% to 15% of the stated number or range. In an example, the term "about" means ±10% of the stated number or value.

[0104] The terms “increased,” “increasing,” or “increase” are generally used herein to mean an increase that is statistically significant. In some respects, the terms “increased” or “increase” mean an increase of at least 10% compared to a reference level, such as an increase of at least about 10%, at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90%, or up to and including 100%, or any increase between 10% and 100%. Other examples of “increase” include increases of at least 2, at least 5, at least 10, at least 20, at least 50, at least 100, at least 1000, or more than 1000 times compared to a reference level.

[0105] The terms “decreased,” “decreasing,” or “decrease” are generally used herein to mean a reduction of a statistically significant amount. In some aspects, “decreased” or “decrease” means a reduction of at least 10% compared to a reference level, such as at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90%, or up to and including 100% (e.g., a lack of level or an undetectable level compared to the reference level), or any reduction between 10% and 100%. In the context of a biomarker or symptom, these terms mean a reduction at a statistically significant level. A reduction can be, for example, at least 10%, at least 20%, at least 30%, at least 40%, or more, and preferably a reduction to a level acceptable within the normal range for an individual without a given disease.

[0106] Although preferred embodiments of the invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. The invention is not intended to be limited to the specific examples provided herein. While the invention has been described with reference to the foregoing description, the description and illustration of embodiments herein are not intended to be construed as limiting. Many variations, modifications, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it should be understood that all aspects of the invention are not limited to the specific depictions, configurations, or relative proportions set forth herein, as this depends on various conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in the practice of the invention. Therefore, the invention is intended to also cover any such alternatives, modifications, variations, or equivalents. The appended claims are intended to define the scope of the invention and thus cover the methods and structures and their equivalents within the scope of these claims.

[0107] Implementation Plan Implementation Scheme 1. A composition comprising: retinoids; and a lipid excipient, wherein the retinoids are present in the composition at a percentage (w / w) of about 0.1% to about 90%.

[0108] Implementation Scheme 2. The composition according to Implementation Scheme 1, wherein the retinoid comprises the structure of Formula I: Each of the numbers 1 to 20 represents a position of carbon covalently bonded to at least one hydrogen, wherein at least one hydrogen is replaced by at least one deuterium.

[0109] Implementation Scheme 3. The composition according to Implementation Scheme 2, wherein R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronide) or R6 (CH2OCHOCH3 or retinyl acetate).

[0110] Implementation Scheme 4. The composition according to Implementation Scheme 2, wherein the carbon in which at least one hydrogen is replaced by at least one deuterium is located at positions 10, 12, 14, 19, 20 or a combination thereof.

[0111] Implementation Scheme 5. The composition according to Implementation Scheme 4, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at position 20.

[0112] Implementation Scheme 6. The composition according to Implementation Scheme 5, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at position 20, said position 20 comprising the substitution of three hydrogen atoms with three deuterium atoms (20, 20, 20-trideuterated retinoids).

[0113] Implementation Scheme 7. The composition according to Implementation Scheme 6, wherein the 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs.

[0114] Implementation Scheme 8. The composition according to Implementation Scheme 7, wherein the 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters.

[0115] Implementation Scheme 9. The composition according to Implementation Scheme 7, wherein the 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol acetate.

[0116] Implementation Scheme 10. The composition according to Implementation Scheme 5, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at position 14 and at position 20, wherein position 14 comprises replacing one hydrogen atom with one deuterium, and position 20 comprises replacing three hydrogen atom with three deuteriums (14, 20, 20, 20-tetradeuterated retinoids).

[0117] Implementation Scheme 11. The composition according to Implementation Scheme 10, wherein the 14,20,20,20-tetradeuterated retinol comprises 14,20,20,20-tetradeuterated retinol analogs.

[0118] Implementation Scheme 12. The composition according to Implementation Scheme 11, wherein the 14,20,20,20-tetradeuterated retinol comprises 14,20,20,20-tetradeuterated retinol esters.

[0119] Implementation Scheme 13. The composition according to Implementation Scheme 11, wherein the 14,20,20,20-tetradeuterated retinol comprises 14,20,20,20-tetradeuterated retinol acetate.

[0120] Implementation Scheme 14. The composition according to Implementation Scheme 5, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at positions 12, 14 and 20, wherein position 12 comprises replacing one hydrogen atom with one deuterium, and position 20 comprises replacing three hydrogen atom with three deuteriums (12, 14, 20, 20, 20-pentadeuterated retinol).

[0121] Implementation Scheme 15. The composition according to Implementation Scheme 14, wherein the 12, 14, 20, 20, 20-pentadeuterated retinols include 12, 14, 20, 20, 20-pentadeuterated retinol analogs.

[0122] Implementation Scheme 16. The composition according to Implementation Scheme 14, wherein the 12, 14, 20, 20, 20-pentadeuterated retinol analogues include 12, 14, 20, 20, 20-pentadeuterated retinol esters.

[0123] Implementation Scheme 17. The composition according to Implementation Scheme 14, wherein the 12, 14, 20, 20, 20-pentadeuterated retinol analogues include 12, 14, 20, 20, 20-pentadeuterated retinol acetate.

[0124] Implementation Scheme 18. The composition according to Implementation Scheme 1, wherein the composition is formulated as a semi-solid.

[0125] Implementation Scheme 19. The composition according to any one of Implementation Schemes 1-18, wherein the composition is formulated as a soft gel capsule.

[0126] Implementation Scheme 20. The composition according to any one of Implementation Schemes 1-17, wherein the composition is formulated as a solid dispersion.

[0127] Implementation Scheme 21. The composition according to any one of Implementation Schemes 1-17, wherein the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

[0128] Implementation Scheme 22. The composition according to any one of Implementation Schemes 1-21, wherein the composition comprises at least one additional ingredient.

[0129] Implementation Scheme 23. The composition according to Implementation Scheme 22, wherein at least one additional component comprises an antioxidant.

[0130] Implementation Scheme 24. The composition according to Implementation Scheme 23, wherein the antioxidant includes vitamin C, vitamin E, zinc, or grape seed extract.

[0131] Implementation Scheme 25. The composition according to Implementation Scheme 22, wherein at least one additional component comprises a fatty acid.

[0132] Implementation Scheme 26. The composition according to Implementation Scheme 25, wherein the fatty acids include ω-3 fatty acids.

[0133] Implementation Scheme 27. The composition according to Implementation Scheme 22, wherein at least one additional component comprises a carotenoid.

[0134] Implementation Scheme 28. The composition according to Implementation Scheme 27, wherein the carotenoids include lutein, zeaxanthin or astaxanthin.

[0135] Implementation Scheme 29. The composition according to Implementation Scheme 22, wherein at least one additional component comprises flavonoids.

[0136] Implementation Scheme 30. The composition according to Implementation Scheme 29, wherein the flavonoids include anthocyanins.

[0137] Implementation Scheme 31. The composition according to Implementation Scheme 22, wherein at least one additional component comprises an amino acid.

[0138] Implementation Scheme 32. The composition according to Implementation Scheme 31, wherein the amino acid includes taurine.

[0139] Implementation Scheme 33. The composition according to any one of Implementation Schemes 1-32, wherein the composition is formulated for ocular application to a subject.

[0140] Implementation Scheme 34. The composition according to any one of Implementation Schemes 1-33, wherein the composition reduces the accumulation of N-sub-retinyl-N-retinylethanolamine (A2E) in the subject.

[0141] Implementation Scheme 35. The composition according to any one of Implementation Schemes 1-34, wherein the composition regulates gene expression in retinal pigment epithelial (RPE) cells.

[0142] Implementation Scheme 36. The composition according to Implementation Scheme 35, wherein the composition increases the bioavailability of retinoids delivered to RPE cells.

[0143] Implementation Scheme 37. The composition according to Implementation Scheme 1, wherein retinoids are present in the composition in a percentage (w / w) of about 0.5% to about 90%.

[0144] Implementation Scheme 38. The composition according to Implementation Scheme 37, wherein retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%.

[0145] Implementation Scheme 39. A method for treating an eye disease or eye condition in a subject, comprising administering a composition comprising: retinoids; and a lipid excipient, wherein the lipid excipient increases the bioavailability of retinoids in the subject by at least 10% compared to the second bioavailability of retinoids formulated with an excipient different from the lipid excipient.

[0146] Implementation Scheme 40. The method according to Implementation Scheme 39, wherein the retinoid comprises the structure of Formula I: Formula I, Each of the numbers 1 to 20 represents a position of carbon covalently bonded to at least one hydrogen, wherein at least one hydrogen is replaced by at least one deuterium.

[0147] Implementation Scheme 41. The method according to Implementation Scheme 40, wherein R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronic acid) or R6 (CH2OCHOCH3 or retinyl acetate).

[0148] Implementation Scheme 42. The method according to Implementation Scheme 40, wherein the carbon in which at least one hydrogen is replaced by at least one deuterium is located at positions 10, 12, 14, 19, 20 or combinations thereof.

[0149] Implementation Scheme 43. The method according to Implementation Scheme 42, wherein the carbon in which at least one hydrogen is replaced by at least one deuterium is at position 20.

[0150] Implementation Scheme 44. The method according to Implementation Scheme 43, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at position 20, said position 20 comprising replacing three hydrogen atoms with three deuterium atoms (20, 20, 20-trideuterated retinol).

[0151] Implementation Scheme 45. The method according to Implementation Scheme 44, wherein 20,20,20-trideuterated retinol includes 20,20,20-trideuterated retinol analogs.

[0152] Implementation Scheme 46. The method according to Implementation Scheme 45, wherein 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters.

[0153] Implementation Scheme 47. The method according to Implementation Scheme 45, wherein 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol acetate.

[0154] Implementation Scheme 48. The method according to Implementation Scheme 44, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at position 14 and at position 20, wherein position 14 comprises replacing one hydrogen atom with one deuterium, and position 20 comprises replacing three hydrogen atom with three deuteriums (14, 20, 20, 20-tetradeuterated retinol).

[0155] Implementation Scheme 49. The method according to Implementation Scheme 48, wherein the 14,20,20,20-tetradeuterated retinol includes 14,20,20,20-tetradeuterated retinol analogs.

[0156] Implementation Scheme 50. The method according to Implementation Scheme 49, wherein 14, 20, 20, 20-tetradeuterated retinols include 14, 20, 20, 20-tetradeuterated retinol esters.

[0157] Implementation Scheme 51. The method according to Implementation Scheme 49, wherein 14,20,20,20-tetradeuterated retinol comprises 14,20,20,20-tetradeuterated retinol acetate.

[0158] Implementation Scheme 52. The method according to Implementation Scheme 44, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at position 12, at position 14 and at position 20, wherein position 12 includes replacing one hydrogen atom with one deuterium, and position 20 includes replacing three hydrogen atom with three deuteriums (12,14, 20, 20, 20-pentadeuterated retinol).

[0159] Implementation Scheme 53. The method according to Implementation Scheme 52, wherein 12, 14, 20, 20, 20-pentadeuterated retinols include 12, 14, 20, 20, 20-pentadeuterated retinol analogs.

[0160] Implementation Scheme 54. The method according to Implementation Scheme 53, wherein the 12, 14, 20, 20, 20-pentadeuterated retinol analogues include 12, 14, 20, 20, 20-pentadeuterated retinol esters.

[0161] Implementation Scheme 55. The method according to Implementation Scheme 53, wherein the 12, 14, 20, 20, 20-pentadeuterated retinol analogues include 12, 14, 20, 20, 20-pentadeuterated retinol acetate.

[0162] Implementation Scheme 56. The method according to Implementation Scheme 39, wherein the composition is formulated as a semi-solid.

[0163] Implementation Scheme 57. The method according to any one of Implementation Schemes 39-56, wherein the composition is formulated into a soft gel capsule.

[0164] Implementation Scheme 58. The method according to any one of Implementation Schemes 39-56, wherein the composition is formulated as a solid dispersion.

[0165] Implementation Scheme 59. The method according to any one of Implementation Schemes 39-56, wherein the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

[0166] Implementation Scheme 60. The method according to any one of Implementation Schemes 39-59, wherein the composition comprises at least one additional ingredient.

[0167] Implementation Scheme 61. The method according to Implementation Scheme 60, wherein at least one additional component comprises an antioxidant.

[0168] Implementation Scheme 62. The method according to Implementation Scheme 61, wherein the antioxidant includes vitamin C, vitamin E, zinc, or grape seed extract.

[0169] Implementation Scheme 63. The method according to Implementation Scheme 60, wherein at least one additional component comprises a fatty acid.

[0170] Implementation Scheme 64. The method according to Implementation Scheme 63, wherein the fatty acids include ω-3 fatty acids.

[0171] Implementation Scheme 65. The method according to Implementation Scheme 60, wherein at least one additional ingredient comprises carotenoids.

[0172] Implementation Scheme 66. The method according to Implementation Scheme 65, wherein the carotenoids include lutein, zeaxanthin or astaxanthin.

[0173] Implementation Scheme 67. The method according to Implementation Scheme 60, wherein at least one additional component comprises flavonoids.

[0174] Implementation Scheme 68. The method according to Implementation Scheme 67, wherein flavonoids include anthocyanins.

[0175] Implementation Scheme 69. The method according to Implementation Scheme 60, wherein at least one additional component comprises an amino acid.

[0176] Implementation Scheme 70. The method according to Implementation Scheme 69, wherein the amino acid includes taurine.

[0177] Implementation Scheme 71. The method according to any one of Implementation Schemes 39-70, wherein the composition is formulated for ocular application to a subject.

[0178] Implementation Scheme 72. The method according to Implementation Scheme 71, wherein an eye disease or eye condition is associated with the accumulation of N-sub-retinyl-N-retinylethanolamine (A2E).

[0179] Implementation Scheme 73. The method according to Implementation Scheme 72 further includes reducing the accumulation of A2E in the subject.

[0180] Implementation Scheme 74. The method according to any one of Implementation Schemes 39-73, wherein the eye disease or eye condition is associated with retinal pigment epithelial (RPE) cells.

[0181] Implementation Scheme 75. The method according to Implementation Scheme 74 further includes regulating gene expression in RPE cells.

[0182] Implementation Scheme 76. The method according to Implementation Scheme 75, wherein gene expression includes the expression of ATP-binding box subfamily A (ABC1) member 4 (ABCA4), very long chain fatty acid extension protein 4 (ELOVL4), or a combination thereof.

[0183] Implementation Scheme 77. The method according to any one of Implementation Schemes 39-76, wherein the eye disease or eye condition is macular degeneration.

[0184] Implementation Scheme 78. The method according to Implementation Scheme 77, wherein macular degeneration includes age-related macular degeneration (AMD), vitrectomycosis, bull's-eye macular degeneration, central serous retinopathy, Charles-Bonnet syndrome (CBS), cone dystrophy, Doyne cellulopathy, diabetic macular edema (DMO), macular hole, macular edema, myopic macular degeneration, pattern dystrophy, pseudoxanthoma elastica (PXE), punctate intrachorioretinopathy (PIC), retinal vein occlusion (RVO), Sotheby's dystrophy, Staggart's disease, geographic atrophy, or combinations thereof.

[0185] Implementation Scheme 79. The method according to Implementation Scheme 78, wherein AMD includes dry AMD.

[0186] Implementation Scheme 80. The method according to Implementation Scheme 78, wherein AMD includes earlier versions of AMD.

[0187] Implementation Scheme 81. The method according to Implementation Scheme 78, wherein the AMD includes wet AMD.

[0188] Implementation Scheme 82. The method according to Implementation Scheme 39, wherein the lipid excipient increases the bioavailability of retinoids in subjects by at least 50% compared to the second bioavailability of retinoids formulated with an excipient different from the lipid excipient.

[0189] Implementation Scheme 83. The method according to Implementation Scheme 82, wherein the lipid excipient increases the bioavailability of retinoids in subjects by 100% compared to the second bioavailability of retinoids formulated with an excipient different from the lipid excipient.

[0190] Implementation Scheme 84. The method according to Implementation Scheme 39, wherein retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%.

[0191] Implementation Scheme 85. Use of the composition, including contacting a subject with the composition, the composition comprising: retinoids; and a lipid excipient, wherein the lipid excipient increases the bioavailability of retinoids in a subject by at least 10% compared to the second bioavailability of retinoids formulated with an excipient different from the lipid excipient, and wherein the use is for non-medical purposes.

[0192] Implementation Scheme 86. The use according to Implementation Scheme 85, wherein the retinoid comprises the structure of Formula I: Formula I, Each of the numbers 1 to 20 represents a position of carbon covalently bonded to at least one hydrogen, wherein at least one hydrogen is replaced by at least one deuterium.

[0193] Implementation Scheme 87. The use according to Implementation Scheme 86, wherein R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid) or R5 (COO-glucuronic acid).

[0194] Implementation Scheme 88. The use according to Implementation Scheme 87, wherein the carbon in which at least one hydrogen is replaced by at least one deuterium is located at positions 10, 12, 14, 19, 20 or a combination thereof.

[0195] Implementation Scheme 89. The use according to Implementation Scheme 88, wherein the carbon in which at least one hydrogen is replaced by at least one deuterium is at position 20.

[0196] Implementation Scheme 90. The use according to Implementation Scheme 89, wherein the carbon in which at least one hydrogen is replaced by at least one deuterium is at position 20, said position 20 comprising replacing three hydrogens by three deuteriums.

[0197] Implementation Scheme 91. The use according to Implementation Scheme 90, wherein the carbon with at least one hydrogen substituted by at least one deuterium is at position 20, said position 20 comprising the substitution of three hydrogens by three deuteriums (20, 20, 20-trideuterated retinol).

[0198] Implementation Scheme 92. The use according to Implementation Scheme 91, wherein 20,20,20-trideuterated retinol includes 20,20,20-trideuterated retinol analogs.

[0199] Implementation Scheme 93. The use according to Implementation Scheme 92, wherein 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol esters.

[0200] Implementation Scheme 94. The use according to Implementation Scheme 92, wherein 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol acetate.

[0201] Implementation Scheme 95. The use according to Implementation Scheme 90, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at position 14 and at position 20, wherein position 14 comprises replacing one hydrogen atom with one deuterium, and position 20 comprises replacing three hydrogen atom with three deuteriums (14, 20, 20, 20-tetradeuterated retinol).

[0202] Implementation Scheme 96. The use according to Implementation Scheme 95, wherein the 14,20,20,20-tetradeuterated retinol includes 14,20,20,20-tetradeuterated retinol analogs.

[0203] Implementation Scheme 97. The use according to Implementation Scheme 96, wherein the 14,20,20,20-tetradeuterated retinol comprises 14,20,20,20-tetradeuterated retinol esters.

[0204] Implementation Scheme 98. The use according to Implementation Scheme 96, wherein the 14,20,20,20-tetradeuterated retinol comprises 14,20,20,20-tetradeuterated retinol acetate.

[0205] Implementation Scheme 99. The use according to Implementation Scheme 90, wherein the carbon with at least one hydrogen atom replaced by at least one deuterium is at position 12, at position 14 and at position 20, wherein position 12 includes replacing one hydrogen atom with one deuterium, and position 20 includes replacing three hydrogen atom with three deuteriums (12,14, 20, 20, 20-pentadeuterated retinol).

[0206] Implementation Scheme 100. The use according to Implementation Scheme 99, wherein 12, 14, 20, 20, 20-pentadeuterated retinols include 12, 14, 20, 20, 20-pentadeuterated retinol analogs.

[0207] Implementation Scheme 101. The use according to Implementation Scheme 100, wherein the 12, 14, 20, 20, 20-pentadeuterated retinol analogues include 12, 14, 20, 20, 20-pentadeuterated retinol esters.

[0208] Implementation Scheme 102. The use according to Implementation Scheme 100, wherein the 12, 14, 20, 20, 20-pentadeuterated retinol analogues include 12, 14, 20, 20, 20-pentadeuterated retinol acetate.

[0209] Implementation scheme 103. The use as described in implementation scheme 85, wherein the use is for aesthetic purposes.

[0210] Implementation Scheme 104. The use as described in Implementation Scheme 85, wherein the use is a cosmetic use.

[0211] Implementation Scheme 105. Use as described in Implementation Scheme 85, wherein the use is a supplementary use.

[0212] Implementation Scheme 106. Use according to any one of Implementation Schemes 85-105, wherein the use does not treat a disease or condition.

[0213] Implementation Scheme 107. Use according to any one of Implementation Schemes 85-106, wherein the composition is formulated for transdermal delivery of retinoids to a subject.

[0214] Implementation Scheme 108. The use according to any one of Implementation Schemes 85-107, wherein the composition is formulated as a semi-solid.

[0215] Implementation Scheme 109. The use according to any one of Implementation Schemes 85-107, wherein the composition is formulated as a soft gel capsule.

[0216] Implementation Scheme 110. The use according to any one of Implementation Schemes 85-107, wherein the composition is formulated as a solid dispersion.

[0217] Implementation Scheme 111. Use according to any one of Implementation Schemes 85-107, wherein the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

[0218] Embodiment 112. The use according to any one of embodiments 85-111, wherein the composition comprises at least one additional ingredient.

[0219] Implementation Scheme 113. The use according to Implementation Scheme 112, wherein at least one additional component comprises an antioxidant.

[0220] Implementation Scheme 114. The use according to Implementation Scheme 113, wherein the antioxidant includes vitamin C, vitamin E, zinc or grape seed extract.

[0221] Implementation Scheme 115. The use according to Implementation Scheme 112, wherein at least one additional ingredient comprises fatty acids.

[0222] Implementation Scheme 116. The use according to Implementation Scheme 115, wherein the fatty acids include ω-3 fatty acids.

[0223] Implementation Scheme 117. The use according to Implementation Scheme 112, wherein at least one additional ingredient comprises carotenoids.

[0224] Implementation Scheme 118. The use according to Implementation Scheme 117, wherein the carotenoids include lutein, zeaxanthin or astaxanthin.

[0225] Implementation Scheme 119. The use according to Implementation Scheme 112, wherein at least one additional component comprises flavonoids.

[0226] Implementation Scheme 120. The use according to Implementation Scheme 119, wherein the flavonoids include anthocyanins.

[0227] Implementation Scheme 121. The use according to Implementation Scheme 112, wherein at least one additional component comprises an amino acid.

[0228] Implementation Scheme 122. The use according to Implementation Scheme 121, wherein the amino acid includes taurine.

[0229] Implementation Scheme 123. The use according to Implementation Scheme 85, wherein retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%.

[0230] Implementation Scheme 124. The use according to Implementation Scheme 85, wherein the lipid excipient increases the bioavailability of retinoids in subjects by 100% compared to the second bioavailability of retinoids formulated with excipients different from lipid excipients.

[0231] Implementation Scheme 125. Use according to any one of Implementation Schemes 85-124, wherein the composition is formulated as a supplement.

[0232] Example The following illustrative examples represent implementations of the stimuli, systems, and methods described herein and are not intended to be limiting in any way.

[0233] Example 1. Preparation of retinoid composition The compositions described herein can be formulated as oil-based capsules, wherein the retinoids are soluble in a carrier oil. Non-limiting examples of carrier oils include soybean oil, sunflower oil, safflower oil, or fish oil. The choice of carrier oil can adjust the stability, bioavailability, or shelf life of the retinoids. The retinoids can be mixed with the carrier oil. The mixture can then be encapsulated in a soft gel capsule shell made of gelatin or other suitable material.

[0234] The composition may also include additional excipients to increase water solubility or retinoid bioavailability. For example, hydroxypropyl-β-cyclodextrin (HPBCD) or nanoparticles (e.g., lipid nanoparticles, nanomicelles, nanocapsules, or nanospheres) may be added to the composition. The inclusion of HPBCD can increase the water solubility of retinoids.

[0235] The composition can also be formulated as a polymer or dispersion, wherein the composition comprises hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, polyvinylpyrrolidone-vinyl acetate, hydroxypropyl methylcellulose-acetic acid-succinate, or any mixture thereof. The polymer or dispersion may be further processed by rapid evaporation, spray drying, precipitation, or melt extrusion to obtain an amorphous composition. The compositions described herein can also be formulated as liquid capsules, oil-in-water emulsions, or lipid matrices. The composition can be formulated as a solid dispersion. For example, retinoids can be incorporated into poly(lactic-co-glycolic acid) (PLGA) millimeter cylindrical implants.

[0236] Example 2. Safety Study The compositions described herein can be studied in twenty (20) healthy human subjects to determine the safety of compositions comprising retinoids, lipid excipients, ingredients, or combinations thereof. The concentration of retinoids in the composition can be adjusted to facilitate the volume or dose to be administered. Compositions of retinoids in multiple doses can be prepared for the range of administration studied. The composition can be administered orally to subjects in a single dose or in escalating doses. Adverse events in subjects can be examined after administration of the composition. Examples of adverse events may include headache, facial flushing, facial burning sensation, or any symptoms associated with hypervitaminosis.

[0237] Example 3. Efficacy Study Studies of the compositions described herein can be conducted to determine the efficacy of oral administration of the compositions described herein to subjects with an eye disease or condition (e.g., macular degeneration). Subjects may orally receive a loading dose of the composition once daily for one or more days. Treatment may be administered on an outpatient basis. During the study, subjects may be asked to limit strenuous physical activity to reduce laboratory variability and avoid excessive vitamin A intake to minimize the influence of external factors on the assessment of safety variables.

[0238] Each subject's two eyes can be evaluated separately. Assessment of visual function may include: best-corrected visual acuity testing using the Early Treatment Diabetic Retinopathy Study (ETDRS) test, followed by low-contrast or high-contrast Smith-Kettlewell Institute low-brightness (SKILL) charts; visual field testing using the Goldmann visual field test; full-field electroretinography (ERG); or full-field stimulation threshold testing (FST). In vivo retinal microscopy can be performed using optical coherence tomography (OCT), and fundus autofluorescence can be determined using Spectralis. Efficacy can be measured by comparing the results of pre-treatment objective and subjective visual function tests with the results of the same parameters obtained during and after oral administration of the composition. Baseline ERG, ETDRS, and SKILL tests can be repeated. Visual function testing can be performed one or more days during and after treatment.

[0239] Example 4. 20,20,20-Trideuterated Retinoids Studies can be conducted on compositions comprising 20,20,20-trideuterated retinoids (e.g., Gildeuretinol or C20-D3-retinyl acetate) as described herein to determine the safety and therapeutic efficacy of 20,20,20-trideuterated retinoids. 20,20,20-trideuterated retinoids can be 20,20,20-trideuterated retinol, 20,20,20-trideuterated retinol ester, 20,20,20-trideuterated retinol acetate, 20,20,20-trideuterated retinaldehyde, 20,20,20-trideuterated pro-vitamin A carotenoids, or combinations thereof.

[0240] Safety studies may include administering a composition containing 20,20,20-trideuterated retinoids to twenty (20) healthy human subjects to determine the safety of compositions containing retinoids, lipid excipients, ingredients, or combinations thereof. The concentration of retinoids in the composition may be adjusted to facilitate the volume or dose to be administered. Compositions in multiple doses of retinoids may be prepared for the range of administration studied. The composition may be administered orally to subjects in a single dose or in escalating doses. Adverse events may be examined in subjects after administration of the composition. Examples of adverse events may include headache, facial flushing, facial burning sensation, or any symptoms associated with hypervitaminosis.

[0241] Efficacy studies can be conducted by administering 20,20,20-trideuterated retinol to subjects with eye diseases or conditions (e.g., macular degeneration). Subjects may receive a loading dose of the composition orally once daily for one or more days. Treatment may be administered on an outpatient basis. During the study, subjects may be asked to limit strenuous physical activity to reduce laboratory variability and avoid excessive vitamin A intake to minimize the influence of external factors on the assessment of safety variables.

[0242] Each subject's two eyes can be assessed separately. Assessment of visual function may include: best-corrected visual acuity testing using the Early Treatment Diabetic Retinopathy Study (ETDRS) test, followed by low-contrast or high-contrast Smith-Kettlewell Institute low-brightness (SKILL) charts; visual field testing using the Goldmann visual field test; full-field electroretinography (ERG); or full-field stimulation threshold testing (FST). In vivo retinal microscopy can be performed using optical coherence tomography (OCT), and fundus autofluorescence can be determined using Spectralis. Efficacy can be measured by comparing the results of pre-treatment objective and subjective visual function tests with the results of the same parameters obtained during and after oral administration of the composition. Baseline ERG, ETDRS, and SKILL tests can be repeated. Visual function tests can be performed one or more days during and after treatment.

[0243] Example 5. Aesthetic, cosmetic, or supplementary uses The retinoids described herein, such as 20,20,20-trideuterated retinoids (e.g., Gildeuretinol or C20-D3-retinyl acetate), can be formulated into compositions or supplements for aesthetic or cosmetic purposes. Retinoids can be formulated as topical creams or ointments for application to a subject for transdermal use. Retinoids can be formulated as soft gel capsules for oral administration. Retinoids can be used for aesthetic, cosmetic, or supplemental purposes where the subject does not use retinoids to treat a disease or condition. Retinoids can be used for aesthetic, cosmetic, or supplemental purposes where retinoids or any other ingredient in a composition containing retinoids does not require regulatory approval.

[0244] Example 6. Lipid-based formulation for retinoid storage and delivery Several lipid-based formulations were tested to develop and improve the bioavailability of retinoids after delivery to subjects with appropriate needs. The lipid formulations tested included 10 mg of lutein, 300 mg of eicosapentaenoic acid (EPA), 110 mg of docosahexaenoic acid (DHA), 2 mg of zeaxanthin, and 50 mg of curcumin. Table 1 summarizes the testing of the lipid-based formulations. As shown in Table 1, F21 exhibits improved retinoid bioavailability. F21 consists of: 2.5 mg of deuterated vitamin A, 10 mg of lutein, 2 mg of zeaxanthin, 50 mg of curcumin, 300 mg of EPA, 110 mg of DHA in 0.1 mL Capmul MCM, 0.1 mL of Gelucire 44 / 14, 0.3 mL of Tween 80, and 0.1 mL of PEG 400. Table 2 illustrates non-limiting examples of excipients as part of lipid-based formulations. Table 3 illustrates examples of ultra-high performance liquid chromatography (UPLC) methods used to obtain materials for formulating the lipid-based formulations described herein.

[0245] Table 1. Summary of lipid-based formulation testing Table 2. Non-limiting examples of excipients or surfactants Table 3. UPLC of materials used to obtain lipid-based formulations Weigh retinol-d6 and add a diluent (e.g., methanol) to dissolve it as a reference standard. The target concentration is 0.1 mg / mL. The standard solution was prepared in duplicate. One was used as the working standard solution (STD), and the other was used as the test standard solution (STD-test). The working standard solution (STD) was diluted 2,000 times as the sensitivity solution (LOQ). The results for system suitability and linearity are shown in Table 4 and Figure 1 As shown in Table 4 and... Figure 1 As shown in the figure, increased sensitivity, precision, accuracy, and linearity were obtained and observed.

[0246] Table 4. Results of the system suitability tests used for determination “N” is the theoretical plate count for retinol-d6.

[0247] “T” is the tailing factor of the main peak of retinol-d6.

[0248] “Rs” is the resolution factor between the main peak and its adjacent peaks.

[0249] The LOQ for retinol-d6 is 0.05 μg / mL.

[0250] Different solvents were gradually added to the six components (curcumin, lutein, zeaxanthin, DHA, EPA, and retinol-d6), and the approximate solubility was obtained by vortexing combined with visual observation. The results are summarized in Table 5.

[0251] Table 5. Approximate solubility of curcumin, lutein, zeaxanthin, DHA, EPA and retinol-d6 Excipients with high solubility and listed in the FDA Inactive Ingredient Guidance Database are preferred for lipid formulation development. Curcumin and zeaxanthin showed good solubility in Gelucire 44 / 14, Gelucire 48 / 16, PEG 400, DMA, and Transcutol HP. DHA and EPA showed good miscibility with most surfactants and solvents except glycols. Retinol-d6 showed good solubility in EPA. For lutein, no surfactant or cosolvent with suitable solubility was found. However, lutein showed high solubility in DMA, Capmul MCM, and Capryol 90. DMA and Capryol 90, with their high toxicity, were not used in formulation development. Gelucire 44 / 14, Gelucire 48 / 16, PEG 400, Transcutol HP, and Capmul MCM were selected to improve solubility in formulations.

[0252] Appearance of lipid formulations Lipid formulations were developed based on a preliminary formulation-01 without retinol-d6. Oils, surfactants, and co-solvents were added to dissolve all components of the preliminary formulation-01. Media without the components of the preliminary formulation were prepared to observe whether the formulations would solidify or precipitate. Since solid components may not dissolve with stirring at room temperature (20°C–25°C) within 20 hours, all formulations were prepared at 40°C to accelerate the preparation time. The appearance of the compositions added to the preliminary formulation-01 and the first round of formulations is recorded in Table 6. The appearance of the formulations and corresponding media is shown in Table 6. Figure 2 As shown in the figure, all lipid formulations were clear at 40°C, but F02-F10 rapidly solidified at room temperature (20°C-25°C) in less than 2 hours. F11-F17 remained liquid at room temperature for a longer period and were further run in dilution studies.

[0253] Table 6. Composition and appearance of lipid formulations selected in the first round of screening Note: Preheat Gelucire 48 / 16 and Gelucire 44 / 14 to 50°C before adding. Dilution test for formulations without retinol-d6 The previously prepared formulations were used directly for dilution tests. All lipid formulations were diluted 1:9 (v / v) with SGF while stirring at 300 rpm and 37°C for 0.5 h, and then diluted 1:3 (v / v) with FaSSIF under the same conditions for 1 h. Appearance, power spectral density (PSD), and pH were recorded. Results are shown in Table 7 and... Figure 3 As shown in the figure. In the dilution study, F12 showed a good particle size distribution (PDI=0.299), while F15 showed a better appearance (almost clear solution).

[0254] Table 7. Dilution studies of the first-round lipid formulation without retinol-d6 Dilution test of formulations containing retinol-d6 Each previously prepared formulation was thoroughly mixed with 2.5 mg of retinol-d6 for dilution testing. The amount of retinol-d6 added was adjusted according to the formulation volume. A control was prepared by adding 2.5 mg of retinol-d6 to 3.6 mL of corn oil and mixing thoroughly. All lipid formulations containing retinol-d6 were diluted with SGF and FaSSIF. Results are shown in Table 8 and... Figure 4 As shown in the figure, F12, F14 and F17 exhibit good particle size distribution, and their polydispersity indices (PDI) are 0.299, 0.268 and 0.263, respectively.

[0255] Table 8. Dilution studies of the first-round lipid formulations containing retinol-d6 Second round of formulation screening To reduce the overall volume of the formulation to less than 1.3 mL (which can be contained in a single soft gel), a second-round lipid formulation in suspension form was developed. Simultaneously, the proportion of Gelucire was reduced to maintain the liquid state of the formulation, as Gelucire hardens at room temperature. The preliminary formulation to be tested-02 included 2.5 mg of retinol-d6, 10 mg of lutein, 2 mg of zeaxanthin, and 50 mg of curcumin.

[0256] Appearance of lipid formulations A lipid formulation was developed based on a preliminary formulation-02 that does not contain retinol-d6. 300 mg of EPA and 110 mg of DHA were added to the formulation as oil components. Other oils, surfactants, and co-solvents were added to the formulation to aid in the dissolution of the solid components. A mediator free of components from the preliminary formulation-02 was prepared to help observe whether the formulation would solidify.

[0257] The appearance of the composition added to the initial formulation-02 and the second-round formulation is recorded in Table 9. The appearance of the formulation and the corresponding mediator is shown in Table 9. Figure 5As shown in the figure. All lipid formulations remained in a reddish-brown suspension for 4 days (4d) at RT (20-25°C). However, 18% of the mediators showed a tendency to solidify.

[0258] Table 9. Composition and appearance of lipid formulations in the second round of screening Preheat Gelucire 48 / 16 and Gelucire 44 / 14 to 50°C before adding. Dilution test for formulations without retinol-d6 The previously prepared formulations were used directly for dilution tests. All lipid formulations were diluted 1:9 (v / v) with SGF while stirring at 300 rpm at 37°C for 0.5 h, and then diluted 1:3 (v / v) with FaSSIF under the same conditions for 1 h. Appearance, PSD, and pH were recorded. All results are shown in Table 10 and... Figure 6 As shown in the figure. In dilution studies containing lutein, zeaxanthin, and curcumin but without retinol-d6, F22 showed a good PDI. F18-F22 showed suspensions with a coarse-particle state after dilution with SGF and FaSSIF. PSD results were significantly affected by the presence of insoluble substances, resulting in multiple peaks and poor data quality. Therefore, lutein, zeaxanthin, and curcumin were excluded in the following dilution studies involving retinol-d6 to avoid their influence.

[0259] F22 showed a good particle size distribution in the dilution study (PDI = 0.275). However, F18-F22 showed a suspension with coarse particles after dilution with SGF and FaSSIF. The PSD results were significantly affected by the presence of insoluble substances, resulting in multiple peaks and poor data quality. Therefore, lutein, zeaxanthin, and curcumin were excluded in the following dilution studies involving retinol-d6 to avoid their influence.

[0260] Table 10. Dilution studies of second-round lipid formulations without retinol-d6 Preheat Gelucire 48 / 16 and Gelucire 44 / 14 to 50°C before adding. Dilution test of formulations containing retinol-d6 Each previously prepared medium was thoroughly mixed with 2.5 mg of retinol-d6 for dilution testing. Because F18 has a tendency to solidify, F18 was removed and F23 was added in the dilution study with retinol-d6. Results for appearance, PSD, and pH are shown in Table 11 and... Figure 7As shown in the figure, F23 remained liquid without solidification for 2 days at RT (20-25°C). After dilution with SGF and FaSSIF, F21 showed a better appearance (blue light microemulsion), and F22 showed a good particle size distribution (PDI=0.290). Therefore, digestion and stability studies were conducted on F21 and F22.

[0261] Table 11. Dilution study of second-round lipid formulations containing retinol-d6 Preheat Gelucire 48 / 16 and Gelucire 48 / 16 to 50°C before adding. Lipolysis tests of F21 and F22 The formulation of F21 includes 2.5 mg of retinol-d6, 10 mg of lutein, 2 mg of zeaxanthin, 50 mg of curcuminoids, 300 mg of EPA, 110 mg of DHA, 0.1 mL of Capmul MCM, 0.1 mL of Gelucire 44 / 14, 0.3 mL of Tween 80, and 0.1 mL of PEG 400. The formulation of F22 includes 2.5 mg of retinol-d6, 10 mg of lutein, 2 mg of zeaxanthin, 50 mg of curcuminoids, 300 mg of EPA, 110 mg of DHA, 0.1 mL of Capmul MCM, 0.1 mL of Gelucire 44 / 14, 0.3 mL of Kolliphor EL, and 0.1 mL of Transcutol HP. Lipolysis of F21 and F22, which exhibit good dilution properties, was tested. 2.5 mg of retinol-d6 was added to 1 mL of corn oil and mixed thoroughly as a control for the lipolysis test. The lipid formulation was dispersed in FaSSIF at 37 °C, and then the pancreatic enzyme extract solution was added after 30 minutes. At each time point (15 and 30 minutes in FaSSIF, and 5, 15, 30, and 60 minutes in the pancreatic enzyme extract solution), 0.5 mL of the suspension was added to 5 μL of 1 M 4-bromophenylboronic acid solution to inhibit lipolysis, and the supernatant was measured. The phenomena and final pH at 30 minutes were recorded. The results are summarized in Table 12. F21 and F22 showed significant effects, with solubility in FaSSIF improved by approximately 20-fold and 17-fold, respectively, at 30 minutes. After the addition of the pancreatic enzyme extract solution, F21 and F22 maintained higher concentrations of 11.2 μg / mL and 7.6 μg / mL, respectively, at 90 minutes, while retinol-d6 in corn oil was 0.43 μg / mL. F21 and F22 showed significant effects, improving the solubility of FaSSIF by approximately 20-fold and 17-fold, respectively, at 30 minutes. After the addition of the pancreatic enzyme extract solution, F21 and F22 maintained high concentrations of 11.2 μg / mL and 7.6 μg / mL for 60 minutes, respectively, while retinol-d6 in corn oil was 0.43 μg / mL.

[0262] Table 12. Lipolysis results of lipid-based formulations Stability tests of F-21 and F-22 The one-week stability of F21 and F22 was tested at 2℃–8℃ and RT (20℃–25℃), respectively. For purity method development (see...), please refer to... Figure 8The placebo (without retinol-d6) contained numerous UPLC peaks in Method-01, affecting the evaluation of retinol-d6-related substances. After optimizing the method for isolating retinol-d6 from the placebo, Method-02 was used to isolate the main peak of retinol-d6, but more impurity peaks appeared. These impurity peaks were still affected by the placebo peaks, making it difficult to test the purity of retinol-d6 in the formulation. Since it is difficult to evaluate the stability of the formulation by purity, the concentration of effective retinol-d6 in the formulation was tested at different time points to assess the stability of the formulation. The results are shown in Tables 13-15. Under 2℃-8℃ / dark / closed conditions, the concentration of retinol-d6 showed no significant change for 7 days in F21, but decreased by 18.2% from day 1 in F22. Under 25℃ / dark / closed conditions, the concentration of retinol-d6 decreased by 7.6% and 25.3% from day 1 in F21 and F22, respectively. Therefore, F21 is stable at 2℃–8℃ in darkness and under sealed conditions, but unstable at 25℃ in darkness and under sealed conditions. F22 is unstable under both 2℃–8℃ in darkness and under sealed conditions and 25℃ in darkness and under sealed conditions. F21, with its good stability, is recommended for PK studies. Under 2℃–8℃ in darkness and under sealed conditions, the concentration of retinol-d6 showed no significant change over 7 days in F21, but changed by 18.2% from day 1 in F22. Under 25℃ in darkness and under sealed conditions, the concentration of retinol-d6 changed by 7.6% and 25.3% from day 1 in F21 and F22, respectively. Therefore, F21 is stable at 2℃–8℃ in darkness and under sealed conditions, but unstable at 25℃ in darkness and under sealed conditions. F22 is unstable under both 2℃–8℃ in darkness and under sealed conditions and 25℃ in darkness and under sealed conditions.

[0263] Table 13. Stability Tests of F21 and F22 Table 14. Stability Tests of F21 and F22 Table 15. Stability Tests of F21 and F22 Table 16 illustrates the solubility screening of lipid-based formulations or emulsions in Example 6, where lutein showed better solubility in Capmul MCM and Capryol 90. Table 17 illustrates formulations 1-17 (F1-F17). All lipid formulations were prepared at 40°C, but F02-F10 rapidly solidified (<2 hours). Formulations F11-F17 remained liquid for longer periods at room temperature (20°C-25°C) and continued dilution studies were conducted. Table 18 illustrates the lipid-based emulsion formulation studies with retinol-d6. Table 19 illustrates the lipid-based emulsion formulation studies without retinol-d6. Tables 20-22 illustrate the second round of formulation screening. All lipid formulations remained a reddish-brown suspension for 4 days at room temperature (RT) (20°C-25°C), but the medium in 18 showed a tendency to solidify. Table 23 illustrates non-limiting examples of formulations for the delivery of retinoids to humans.

[0264] Table 16. Solubility Screening Table 17. Research on lipid-based emulsion formulations Table 18. Studies of lipid-based emulsion formulations in the presence of retinol-d6 Table 19. Studies of lipid-based emulsion formulations in the absence of retinol-d6 Table 20. Second Round of Formulation Screening Table 21. Second round of formulation screening Table 22. Second round of formulation screening Table 23. Formulations for retinol delivery in humans Table 24 summarizes the screening results as described in Example 6. Table 25 illustrates the solubility screening performed with various oils. Lutein showed increased solubility in Capmul MCM and Capryol 90.

[0265] Table 24. Summary of Lipid Formulation Screening Table 25. Research on lipid-based emulsion formulations Table 26 illustrates non-limiting examples of in vivo pharmacokinetic (PK) studies in which rats were administered product A, product B, or product C via oral gavage. Following administration, blood samples were collected to measure circulating retinol-d3 (vitamin A-d3) levels. Figure 9 The figure shows the time-course measurement of retinol-d3 plasma concentration over a 24-hour period. Figure 9 As shown, administration of retinol-d3 via product A did not result in a decrease in the bioavailability of retinol-d3 in vivo.

[0266] Table 26. Formulations used in in vivo pharmacokinetic (PK) studies While the foregoing disclosure has been described in detail for clarity and understanding, those skilled in the art will recognize, upon reading this disclosure, that various changes in form and detail may be made without departing from the true scope of this disclosure. For example, all the technologies and devices described above can be used in various combinations. All publications, patents, patent applications and / or other documents cited in this application are incorporated herein by reference in their entirety for all purposes, as if each individual publication, patent, patent application and / or other document were individually and separately indicated to be incorporated herein by reference for all purposes.

Claims

1. A composition comprising: (a) Retinol-like substances, including the structure of formula I: ； (b) lipid excipients; and (c) Surfactants, The retinoids are present in the composition at a percentage (w / w) of about 0.1% to about 90%.

2. The composition according to claim 1, wherein the retinoid comprises the structure of formula I: ， Each of the numbers 1 to 20 represents a position of carbon covalently bonded to at least one hydrogen, wherein at least one hydrogen is replaced by at least one deuterium.

3. The composition according to claim 2, wherein R comprises R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronic acid) or R6 (CH2OCHOCH3 or retinyl acetate).

4. The composition according to claim 2, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is located at positions 10, 12, 14, 19, 20 or a combination thereof.

5. The composition according to claim 4, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 or at position 20.

6. The composition of claim 5, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 or position 20, said position 19 comprising replacing three hydrogens with three deuteriums (19, 19, 19-trideuterated retinol), said position 20 comprising replacing three hydrogens with three deuteriums (20, 20, 20-trideuterated retinol).

7. The composition of claim 6, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 and at position 20, wherein position 19 comprises replacing three hydrogens with three deuteriums and position 20 comprises replacing three hydrogens with three deuteriums.

8. The composition according to claim 6 or 7, wherein the 19,19,19-trideuterated retinol comprises 19,19,19-trideuterated retinol analogs.

9. The composition of claim 8, wherein the 19,19,19-trideuterated retinol analogue comprises 19,19,19-trideuterated retinol esters.

10. The composition of claim 8, wherein the 19,19,19-trideuterated retinol analogue comprises 19,19,19-trideuterated retinol acetate.

11. The composition according to claim 6 or 7, wherein the 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs.

12. The composition of claim 11, wherein the 20,20,20-trideuterated retinol analogue comprises 20,20,20-trideuterated retinol esters.

13. The composition of claim 11, wherein the 20,20,20-trideuterated retinol analogue comprises 20,20,20-trideuterated retinol acetate.

14. The composition of claim 7, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 and at position 20, wherein position 19 comprises replacing three hydrogens with three deuteriums, and position 20 comprises replacing three hydrogens with three deuteriums (19, 19, 19, 20, 20, 20-hexadeuterated retinol).

15. The composition of claim 14, wherein the 19,19,19,20,20,20-hexadeuterated retinol comprises 19,19,19,20,20,20-hexadeuterated retinol analogs.

16. The composition of claim 15, wherein the 19,19,19,20,20,20-hexadeuterated retinol analogue comprises 19,19,19,20,20,20-hexadeuterated retinol esters.

17. The composition of claim 15, wherein the 19,19,19,20,20,20-hexadeuterated retinol analogue comprises 19,19,19,20,20,20-hexadeuterated retinol acetate.

18. The composition according to any one of claims 1-17, wherein the composition comprises from about 1.0 mg to about 5.0 mg of the retinoid.

19. The composition of claim 18, wherein the composition comprises from about 2.0 mg to about 3.0 mg of the retinoid.

20. The composition of claim 19, wherein the composition comprises about 2.5 mg of the retinoid.

21. The composition of claim 1, wherein the lipid excipient comprises an ω-3 fatty acid.

22. The composition of claim 21, wherein the ω-3 fatty acid comprises eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA).

23. The composition of claim 21, wherein the ω-3 fatty acid comprises EPA and DHA.

24. The composition according to claim 22 or 23, wherein the composition comprises from about 100 mg to about 500 mg of the EPA.

25. The composition of claim 24, wherein the composition comprises from about 200 mg to about 400 mg of the EPA.

26. The composition of claim 25, wherein the composition comprises about 300 mg of the EPA.

27. The composition according to any one of claims 22-26, wherein the composition comprises from about 50 mg to about 200 mg of the DHA.

28. The composition of claim 27, wherein the composition comprises from about 100 mg to about 150 mg of the DHA.

29. The composition of claim 28, wherein the composition comprises about 110 mg of the DHA.

30. The composition according to any one of claims 1-29, wherein the composition comprises at least one additional ingredient.

31. The composition of claim 30, wherein the at least one additional component comprises an antioxidant.

32. The composition of claim 31, wherein the antioxidant comprises vitamin C, vitamin E, zinc, or grape seed extract.

33. The composition according to claim 31, wherein the at least one additional ingredient comprises a curcumin compound.

34. The composition of claim 33, wherein the at least one additional ingredient comprises curcuminoids.

35. The composition of claim 34, wherein the composition comprises from about 20 mg to about 100 mg of the curcuminoid.

36. The composition of claim 35, wherein the composition comprises about 50 mg of the curcuminoid.

37. The composition of claim 30, wherein the at least one additional ingredient comprises a carotenoid.

38. The composition of claim 37, wherein the carotenoid comprises lutein, zeaxanthin, or astaxanthin.

39. The composition of claim 38, wherein the carotenoid comprises lutein and zeaxanthin.

40. The composition of claim 38, wherein the composition comprises from about 1 mg to about 100 mg of the lutein.

41. The composition of claim 38, wherein the composition comprises about 10 mg of the lutein.

42. The composition of claim 38, wherein the composition comprises from about 1 mg to about 10 mg of the zeaxanthin.

43. The composition of claim 42, wherein the composition comprises about 2 mg of the zeaxanthin.

44. The composition of claim 30, wherein the at least one additional component comprises flavonoids.

45. The composition of claim 44, wherein the flavonoids comprise anthocyanins.

46. ​​The composition of claim 30, wherein the at least one additional component comprises an amino acid.

47. The composition of claim 46, wherein the amino acid comprises taurine.

48. The composition of claim 30, wherein the at least one additional component comprises an emulsifier.

49. The composition according to any one of claims 1-48, wherein the surfactant comprises Tween, Kolliphor, Labrasol, Gelucire, Capmul, polyethylene glycol (PEG), Transcutol, Capryol, or a combination thereof.

50. The composition of claim 49, wherein the surfactant comprises the Gelucire, the Capmul, the Tween, and the PEG.

51. The composition according to claim 49 or 50, wherein the Gelucire comprises Gelucire 44 / 14.

52. The composition according to any one of claims 49-51, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Gelucire.

53. The composition of claim 52, wherein the composition comprises about 0.1 mL of the Gelucire.

54. The composition according to claim 49 or 50, wherein the Capmul comprises Capmul MCM.

55. The composition according to any one of claims 49, 50 or 54, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Capmul.

56. The composition of claim 55, wherein the composition comprises about 0.1 mL of the Capmul.

57. The composition according to claim 49 or 50, wherein the Tween comprises Tween 80.

58. The composition according to any one of claims 49, 50 or 57, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Tween.

59. The composition of claim 58, wherein the composition comprises about 0.3 mL of the Tween.

60. The composition according to claim 49 or 50, wherein the PEG comprises PEG 400.

61. The composition according to any one of claims 49, 50 or 60, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the PEG.

62. The composition of claim 61, wherein the composition comprises about 0.1 mL of the PEG.

63. The composition of claim 49, wherein the Kolliphor comprises Kolliphor EL.

64. The composition according to claim 49 or 63, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Kolliphor.

65. The composition of claim 64, wherein the composition comprises about 0.3 mL of the Kolliphor.

66. The composition of claim 49, wherein the Transcutol comprises Transcutol HP.

67. The composition according to claim 49 or 66, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Transcutol.

68. The composition of claim 67, wherein the composition comprises about 0.1 mL of the Transcutol.

69. The composition according to any one of claims 1-68, wherein the composition is formulated as a semi-solid.

70. The composition according to any one of claims 1-68, wherein the composition is formulated as a soft gel capsule.

71. The composition according to any one of claims 1-68, wherein the composition is formulated as a solid dispersion.

72. The composition according to any one of claims 1-68, wherein the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

73. The composition according to any one of claims 1-72, wherein the composition is formulated for ocular application to a subject.

74. The composition of claim 73, wherein the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in the subject.

75. The composition according to any one of claims 1-74, wherein the composition regulates gene expression in retinal pigment epithelial (RPE) cells.

76. The composition of claim 75, wherein the composition increases the bioavailability of the retinoids delivered to the RPE cells.

77. The composition of claim 76, wherein the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability of delivering the retinoid to the RPE cells without the lipid excipient or the surfactant.

78. The composition according to any one of claims 1-77, wherein the composition increases the bioavailability of the retinoid in the subject compared to the second bioavailability of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

79. The composition of claim 78, wherein the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability in the subject.

80. The composition according to any one of claims 1-75, wherein the composition does not reduce the bioavailability of the retinoid in the subject compared to the second bioavailability of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

81. The composition of claim 80, wherein the bioavailability and the second bioavailability are determined by plasma concentrations of the retinoid obtained from the subject.

82. The composition according to any one of claims 1-81, wherein the composition increases the stability of the retinoids compared to the second stability of the retinoids in comparable compositions that do not contain the lipid excipients or the surfactants.

83. The composition of claim 82, wherein the stability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second stability of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

84. The composition according to any one of claims 1-83, wherein the composition increases the solubility of the retinoids compared to the second solubility of the retinoids in a comparable composition that does not contain the lipid excipient or the surfactant.

85. The composition of claim 84, wherein the solubility is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second solubility of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

86. The composition according to any one of claims 1-85, wherein the retinoids are present in the composition in a percentage (w / w) of about 0.5% to about 90%.

87. The composition of claim 86, wherein the retinoids are present in the composition in a percentage (w / w) of about 1% to about 50%.

88. The composition according to any one of claims 1-87 further comprises oil.

89. The composition of claim 84, wherein the oil comprises corn oil, oleic acid, Maisine cc, or a combination thereof.

90. A method for treating an eye disease or eye condition in a subject, the method comprising administering a composition comprising: (a) Retinoids; (b) lipid excipients; and (c) Surfactants, The lipid excipient increases the bioavailability of the retinoid in the subject by at least 10% compared to the second bioavailability of the retinoid formulated with an excipient different from the lipid excipient.

91. The method of claim 90, wherein the retinoid comprises the structure of formula I: Equation I, Each of the numbers 1 to 20 represents a position of carbon covalently bonded to at least one hydrogen, wherein at least one hydrogen is replaced by at least one deuterium.

92. The method according to claim 91, wherein R comprises R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid), R5 (COO-glucuronic acid) or R6 (CH2OCHOCH3 or retinyl acetate).

93. The method of claim 91, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is located at positions 10, 12, 14, 19, 20 or a combination thereof.

94. The method of claim 93, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 or at position 20.

95. The method of claim 94, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 or position 20, the position 19 comprising replacing three hydrogens with three deuteriums (19, 19, 19-trideuterated retinol), and the position 20 comprising replacing three hydrogens with three deuteriums (20, 20, 20-trideuterated retinol).

96. The method of claim 95, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 and at position 20, wherein position 19 comprises replacing three hydrogens with three deuteriums and position 20 comprises replacing three hydrogens with three deuteriums.

97. The method according to claim 95 or 96, wherein the 19,19,19-trideuterated retinol comprises 19,19,19-trideuterated retinol analogs.

98. The method of claim 97, wherein the 19,19,19-trideuterated retinol analogue comprises 19,19,19-trideuterated retinol esters.

99. The method of claim 97, wherein the 19,19,19-trideuterated retinol analogue comprises 19,19,19-trideuterated retinol acetate.

100. The method according to claim 95 or 96, wherein the 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs.

101. The method of claim 100, wherein the 20,20,20-trideuterated retinol analogue comprises 20,20,20-trideuterated retinol esters.

102. The method of claim 100, wherein the 20,20,20-trideuterated retinol analogue comprises 20,20,20-trideuterated retinol acetate.

103. The method of claim 96, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 and at position 20, wherein position 19 comprises replacing three hydrogens with three deuteriums, and position 20 comprises replacing three hydrogens with three deuteriums (19, 19, 19, 20, 20, 20-hexadeuterated retinol).

104. The method of claim 103, wherein the 19,19,19,20,20,20-hexadeuterated retinol comprises 19,19,19,20,20,20-hexadeuterated retinol analogs.

105. The method of claim 104, wherein the 19,19,19,20,20,20-hexadeuterated retinol analogue comprises 19,19,19,20,20,20-hexadeuterated retinol esters.

106. The method of claim 104, wherein the 19,19,19,20,20,20-hexadeuterated retinol analogue comprises 19,19,19,20,20,20-hexadeuterated retinol acetate.

107. The method according to any one of claims 90-106, wherein the composition comprises from about 1.0 mg to about 5.0 mg of the retinoid.

108. The method of claim 107, wherein the composition comprises from about 2.0 mg to about 3.0 mg of the retinoid.

109. The method of claim 108, wherein the composition comprises about 2.5 mg of the retinoid.

110. The method of claim 90, wherein the lipid excipient comprises an ω-3 fatty acid.

111. The method of claim 110, wherein the ω-3 fatty acid comprises eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA).

112. The method of claim 110, wherein the ω-3 fatty acid comprises EPA and DHA.

113. The method according to claim 111 or 112, wherein the composition comprises from about 100 mg to about 500 mg of the EPA.

114. The method of claim 113, wherein the composition comprises from about 200 mg to about 400 mg of the EPA.

115. The method of claim 114, wherein the composition comprises about 300 mg of the EPA.

116. The method according to any one of claims 111-115, wherein the composition comprises from about 50 mg to about 200 mg of the DHA.

117. The method of claim 116, wherein the composition comprises from about 100 mg to about 150 mg of the DHA.

118. The method of claim 117, wherein the composition comprises about 110 mg of the DHA.

119. The method according to any one of claims 90-118, wherein the composition comprises at least one additional ingredient.

120. The method of claim 119, wherein the at least one additional component comprises an antioxidant.

121. The method of claim 120, wherein the antioxidant comprises vitamin C, vitamin E, zinc, or grape seed extract.

122. The method of claim 119, wherein the at least one additional component comprises a curcumin compound.

123. The method of claim 120, wherein the at least one additional component comprises curcuminoids.

124. The method of claim 123, wherein the composition comprises from about 20 mg to about 100 mg of the curcuminoid.

125. The method of claim 124, wherein the composition comprises about 50 mg of the curcuminoid.

126. The method of claim 119, wherein the at least one additional ingredient comprises carotenoids.

127. The method of claim 126, wherein the carotenoid comprises lutein, zeaxanthin, or astaxanthin.

128. The method of claim 127, wherein the carotenoids include lutein and zeaxanthin.

129. The method of claim 127, wherein the composition comprises from about 1 mg to about 100 mg of the lutein.

130. The method of claim 127, wherein the composition comprises about 10 mg of the lutein.

131. The method of claim 127, wherein the composition comprises from about 1 mg to about 10 mg of the zeaxanthin.

132. The method of claim 131, wherein the composition comprises about 2 mg of the zeaxanthin.

133. The method of claim 119, wherein the at least one additional component comprises flavonoids.

134. The method of claim 133, wherein the flavonoids comprise anthocyanins.

135. The method of claim 119, wherein the at least one additional component comprises an amino acid.

136. The method of claim 135, wherein the amino acid comprises taurine.

137. The method of claim 119, wherein the at least one additional component comprises an emulsifier.

138. The method according to any one of claims 90-137, wherein the surfactant comprises Tween, Kolliphor, Labrasol, Gelucire, Capmul, polyethylene glycol (PEG), Transcutol, Capryol, or a combination thereof.

139. The method of claim 138, wherein the surfactant comprises the Gelucire, the Capmul, the Tween, and the PEG.

140. The method of claim 138 or 139, wherein the Gelucire comprises Gelucire 44 / 14.

141. The method according to any one of claims 138-140, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Gelucire.

142. The method of claim 114, wherein the composition comprises about 0.1 mL of the Gelucire.

143. The method of claim 138 or 139, wherein the Capmul comprises Capmul MCM.

144. The method according to any one of claims 138, 139 or 143, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Capmul.

145. The method of claim 144, wherein the composition comprises about 0.1 mL of the Capmul.

146. The method of claim 138 or 139, wherein the Tween comprises Tween 80.

147. The method according to any one of claims 138, 139 or 146, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Tween.

148. The method of claim 147, wherein the composition comprises about 0.3 mL of the Tween.

149. The method of claim 142 or 143, wherein the PEG comprises PEG 400.

150. The method according to any one of claims 138, 139 or 149, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the PEG.

151. The method of claim 150, wherein the composition comprises about 0.1 mL of the PEG.

152. The method of claim 138, wherein the Kolliphor includes Kolliphor EL.

153. The method according to any one of claims 138 or 152, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Kolliphor.

154. The method of claim 153, wherein the composition comprises about 0.3 mL of the Kolliphor.

155. The method of claim 138, wherein the Transcutol comprises Transcutol HP.

156. The method of claim 138 or 155, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Transcutol.

157. The method of claim 156, wherein the composition comprises about 0.1 mL of the Transcutol.

158. The method according to any one of claims 90-157, wherein the composition is formulated as a semi-solid.

159. The method according to any one of claims 90-157, wherein the composition is formulated as a soft gel capsule.

160. The method according to any one of claims 90-157, wherein the composition is formulated as a solid dispersion.

161. The method according to any one of claims 90-157, wherein the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

162. The method according to any one of claims 90-161, wherein the composition is formulated for ocular application to a subject.

163. The method of claim 162, wherein the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in the subject.

164. The method according to any one of claims 90-163, wherein the composition regulates gene expression in retinal pigment epithelial (RPE) cells.

165. The method of claim 164, wherein the composition increases the bioavailability of the retinoids delivered to the RPE cells.

166. The method of claim 165, wherein the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability of delivering the retinoid to the RPE cells without the lipid excipient or the surfactant.

167. The method according to any one of claims 90-166, wherein the composition increases the bioavailability of the retinoids in the subject compared to the second bioavailability of the retinoids in a comparable composition that does not contain the lipid excipient or the surfactant.

168. The method of claim 167, wherein the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability in the subject.

169. The method according to any one of claims 90-165, wherein the composition does not reduce the bioavailability of the retinoid in the subject compared to the second bioavailability of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

170. The method of claim 169, wherein the bioavailability and the second bioavailability are determined by plasma concentrations of the retinoid obtained from the subject.

171. The method according to any one of claims 90-170, wherein the composition increases the stability of the retinoids compared to the second stability of the retinoids in a comparable composition that does not contain the lipid excipient or the surfactant.

172. The method of claim 171, wherein the stability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second stability of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

173. The method according to any one of claims 90-172, wherein the composition increases the solubility of the retinoids compared to the second solubility of the retinoids in a comparable composition that does not contain the lipid excipient or the surfactant.

174. The method of claim 173, wherein the solubility is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second solubility of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

175. The method according to any one of claims 90-174, wherein the retinoids are present in the composition in a percentage (w / w) of about 0.5% to about 90%.

176. The method of claim 175, wherein the retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%.

177. The method according to any one of claims 90-176, wherein the composition further comprises oil.

178. The method of claim 177, wherein the oil comprises corn oil, oleic acid, Maisine cc, or a combination thereof.

179. The method according to any one of claims 90-178, wherein the eye disease or eye condition is associated with the accumulation of N-sub-retinyl-N-retinylethanolamine (A2E).

180. The method of claim 161, further comprising reducing the accumulation of A2E in the subject.

181. The method according to any one of claims 90-180, wherein the eye disease or eye condition is associated with retinal pigment epithelial (RPE) cells.

182. The method of claim 181, further comprising regulating gene expression in the RPE cells.

183. The method of claim 182, wherein the gene expression comprises the expression of ATP-binding box subfamily A (ABC1) member 4 (ABCA4), very long chain fatty acid extension protein 4 (ELOVL4), or a combination thereof.

184. The method according to any one of claims 90-183, wherein the eye disease or eye condition is macular degeneration.

185. The method of claim 184, wherein the macular degeneration includes age-related macular degeneration (AMD), vitrectomycosis, bull's-eye macular degeneration, central serous retinopathy, Charles-Bonnet syndrome (CBS), cone dystrophy, Doyne cellulopathy, diabetic macular edema (DMO), macular hole, macular edema, myopic macular degeneration, pattern dystrophy, pseudoxanthoma elastica (PXE), punctate intrachorioretinopathy (PIC), retinal vein occlusion (RVO), Sotheby's dystrophy, Staggart's disease, geographic atrophy, or combinations thereof.

186. The method of claim 185, wherein the AMD comprises dry AMD.

187. The method of claim 185, wherein the AMD includes earlier AMD.

188. The method of claim 185, wherein the AMD comprises wet AMD.

189. Use of the composition, including contacting a subject with the composition, the composition comprising: (a) Retinoids; (b) lipid excipients; and (c) Surfactants, The lipid excipient increases the bioavailability of the retinoid in the subject by at least 10% compared to the second bioavailability of the retinoid formulated with an excipient different from the lipid excipient. The intended use is non-medical.

190. The use according to claim 189, wherein the retinoid comprises the structure of formula I: ， Each of the numbers 1 to 20 represents a position of carbon covalently bonded to at least one hydrogen, wherein at least one hydrogen is replaced by at least one deuterium.

191. The use according to claim 190, wherein the R includes R1 (CH2OH or retinol), R2 (CH2O-fatty acid or retinyl ester), R3 (CHO or retinaldehyde), R4 (COOH or retinoic acid) or R5 (COO-glucuronic acid).

192. The use according to claim 191, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is located at positions 10, 12, 14, 19, 20 or a combination thereof.

193. The use according to claim 192, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 or at position 20.

194. The use according to claim 193, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 or position 20, the position 19 comprising replacing three hydrogens with three deuteriums (19, 19, 19-trideuterated retinol), and the position 20 comprising replacing three hydrogens with three deuteriums (20, 20, 20-trideuterated retinol).

195. The use according to claim 194, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 and at position 20, wherein position 19 comprises replacing three hydrogens with three deuteriums and position 20 comprises replacing three hydrogens with three deuteriums.

196. The use according to claim 194 or 195, wherein the 19,19,19-trideuterated retinol comprises 19,19,19-trideuterated retinol analogs.

197. The use according to claim 196, wherein the 19,19,19-trideuterated retinol analogue comprises 19,19,19-trideuterated retinol esters.

198. The use according to claim 196, wherein the 19,19,19-trideuterated retinol analogue comprises 19,19,19-trideuterated retinol acetate.

199. The use according to claim 194 or 195, wherein the 20,20,20-trideuterated retinol comprises 20,20,20-trideuterated retinol analogs.

200. The use according to claim 199, wherein the 20,20,20-trideuterated retinol analogue comprises 20,20,20-trideuterated retinol esters.

201. The use according to claim 199, wherein the 20,20,20-trideuterated retinol analogue comprises 20,20,20-trideuterated retinol acetate.

202. The use according to claim 195, wherein the carbon in which the at least one hydrogen is replaced by the at least one deuterium is at position 19 and at position 20, wherein position 19 comprises replacing three hydrogens with three deuteriums, and position 20 comprises replacing three hydrogens with three deuteriums (19, 19, 19, 20, 20, 20-hexadeuterated retinol).

203. The use according to claim 202, wherein the 19,19,19,20,20,20-hexadeuterated retinol comprises 19,19,19,20,20,20-hexadeuterated retinol analogs.

204. The use according to claim 203, wherein the 19,19,19,20,20,20-hexadeuterated retinol analogue comprises 19,19,19,20,20,20-hexadeuterated retinol esters.

205. The use according to claim 203, wherein the 19,19,19,20,20,20-hexadeuterated retinol analogue comprises 19,19,19,20,20,20-hexadeuterated retinol acetate.

206. The use according to any one of claims 189-205, wherein the composition comprises from about 1.0 mg to about 5.0 mg of the retinoid.

207. The use according to claim 206, wherein the composition comprises from about 2.0 mg to about 3.0 mg of the retinoid.

208. The use according to claim 207, wherein the composition comprises about 2.5 mg of the retinoid.

209. The use according to claim 189, wherein the lipid excipient comprises an ω-3 fatty acid.

210. The use according to claim 209, wherein the ω-3 fatty acid comprises EPA or DHA.

211. The use according to claim 210, wherein the ω-3 fatty acid comprises EPA and DHA.

212. The use according to claim 209 or 210, wherein the composition comprises from about 100 mg to about 500 mg of the EPA.

213. The use according to claim 212, wherein the composition comprises from about 200 mg to about 400 mg of the EPA.

214. The use according to claim 213, wherein the composition comprises about 300 mg of the EPA.

215. The use according to any one of claims 210-214, wherein the composition comprises from about 50 mg to about 200 mg of the DHA.

216. The use according to claim 215, wherein the composition comprises from about 100 mg to about 150 mg of the DHA.

217. The use according to claim 216, wherein the composition comprises about 110 mg of the DHA.

218. The use according to any one of claims 189-217, wherein the composition comprises at least one additional ingredient.

219. The use according to claim 218, wherein the at least one additional component comprises an antioxidant.

220. The use according to claim 219, wherein the antioxidant comprises vitamin C, vitamin E, zinc, or grape seed extract.

221. The use according to claim 218, wherein the at least one additional ingredient comprises a curcumin compound.

222. The use according to claim 218, wherein the at least one additional ingredient comprises curcuminoids.

223. The use according to claim 222, wherein the composition comprises from about 20 mg to about 100 mg of the curcuminoid.

224. The use according to claim 223, wherein the composition comprises about 50 mg of the curcuminoid.

225. The use according to claim 218, wherein the at least one additional ingredient comprises carotenoids.

226. The use according to claim 225, wherein the carotenoid comprises lutein, zeaxanthin, or astaxanthin.

227. The use according to claim 226, wherein the composition comprises from about 1 mg to about 100 mg of the lutein.

228. The use according to claim 227, wherein the composition comprises about 10 mg of the lutein.

229. The use according to claim 226, wherein the composition comprises from about 1 mg to about 10 mg of the zeaxanthin.

230. The use according to claim 229, wherein the composition comprises about 2 mg of the zeaxanthin.

231. The use according to claim 218, wherein the at least one additional component comprises flavonoids.

232. The use according to claim 231, wherein the flavonoids include anthocyanins.

233. The use according to claim 218, wherein the at least one additional component comprises an amino acid.

234. The use according to claim 233, wherein the amino acid comprises taurine.

235. The use according to claim 218, wherein the at least one additional component comprises an emulsifier.

236. The use according to any one of claims 189-235, wherein the surfactant comprises Tween, Kolliphor, Labrasol, Gelucire, Capmul, PEG, Transcutol, Capryol or a combination thereof.

237. The use according to claim 236, wherein the surfactant comprises the Gelucire, the Capmul, the Tween, and the PEG.

238. The use according to claim 236 or 237, wherein the Gelucire comprises Gelucire 44 / 14.

239. The use according to any one of claims 236-238, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Gelucire.

240. The use according to claim 239, wherein the composition comprises about 0.1 mL of the Gelucire.

241. The use according to claim 236 or 237, wherein the Capmul comprises Capmul MCM.

242. The use according to any one of claims 236, 237 or 241, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Capmul.

243. The use according to claim 242, wherein the composition comprises about 0.1 mL of the Capmul.

244. The use according to claim 236 or 237, wherein the Tween includes Tween 80.

245. The use according to any one of claims 236, 237 or 244, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Tween.

246. The use according to claim 245, wherein the composition comprises about 0.3 mL of the Tween.

247. The use according to claim 236 or 237, wherein the PEG comprises PEG 400.

248. The use according to any one of claims 236, 237 or 247, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the PEG.

249. The use according to claim 248, wherein the composition comprises about 0.1 mL of the PEG.

250. The use according to claim 236, wherein the Kolliphor includes Kolliphor EL.

251. The use according to claim 236 or 250, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Kolliphor.

252. The use according to claim 251, wherein the composition comprises about 0.3 mL of the Kolliphor.

253. The use according to claim 236, wherein the Transcutol comprises Transcutol HP.

254. The use according to claim 236 or 253, wherein the composition comprises from about 0.05 mL to about 0.5 mL of the Transcutol.

255. The use according to claim 254, wherein the composition comprises about 0.1 mL of the Transcutol.

256. The use according to any one of claims 189-255, wherein the composition is formulated as a semi-solid.

257. The use according to any one of claims 189-255, wherein the composition is formulated as a soft gel capsule.

258. The use according to any one of claims 189-255, wherein the composition is formulated as a solid dispersion.

259. The use according to any one of claims 189-255, wherein the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

260. The use according to any one of claims 189-259, wherein the composition is formulated for ocular application to a subject.

261. The use according to claim 260, wherein the composition reduces the accumulation of N-retinyl-N-retinylethanolamine (A2E) in the subject.

262. The use according to any one of claims 189-261, wherein the composition regulates gene expression in retinal pigment epithelial (RPE) cells.

263. The use according to claim 262, wherein the composition increases the bioavailability of the retinoids delivered to the RPE cells.

264. The use according to claim 263, wherein the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability of delivering the retinoid to the RPE cells without the lipid excipient or the surfactant.

265. The use according to any one of claims 189-264, wherein the composition increases the stability of the retinoids compared to the second stability of the retinoids in comparable compositions that do not contain the lipid excipients or the surfactants.

266. The use according to claim 265, wherein the stability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second stability of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

267. The use according to any one of claims 189-266, wherein the composition increases the bioavailability of the retinoid in the subject compared to the second bioavailability of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

268. The use according to claim 267, wherein the bioavailability is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second bioavailability in the subject.

269. The use according to any one of claims 189-265, wherein the composition does not reduce the bioavailability of the retinoid in the subject compared to the second bioavailability of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

270. The use according to claim 269, wherein the bioavailability and the second bioavailability are determined by plasma concentrations of the retinoid obtained from the subject.

271. The use according to any one of claims 189-270, wherein the composition increases the solubility of the retinoids compared to the second solubility of the retinoids in a comparable composition that does not contain the lipid excipient or the surfactant.

272. The use according to claim 271, wherein the solubility is increased by at least 10%, at least 50%, at least 100%, or at least 500% compared to the second solubility of the retinoid in a comparable composition that does not contain the lipid excipient or the surfactant.

273. The use according to any one of claims 189-272, wherein the retinoids are present in the composition in a percentage (w / w) of about 0.5% to about 90%.

274. The use according to claim 273, wherein the retinoids are present in the composition at a percentage (w / w) of about 1% to about 50%.

275. The use according to any one of claims 189-274, wherein the composition comprises an oil.

276. The use according to claim 275, wherein the oil comprises corn oil, oleic acid, Maisine cc, or a combination thereof.

277. The use according to any one of claims 189-276, wherein the use is an aesthetic use.

278. The use according to any one of claims 189-276, wherein the use is a cosmetic use.

279. The use according to any one of claims 189-276, wherein the use is a supplement use.

280. The use according to any one of claims 189-276, wherein the use does not treat a disease or condition.

281. The use according to any one of claims 189-276, wherein the composition is formulated for transdermal delivery of the retinoid to the subject.

282. The use according to any one of claims 189-281, wherein the composition is formulated as a semi-solid.

283. The use according to any one of claims 189-281, wherein the composition is formulated as a soft gel capsule.

284. The use according to any one of claims 189-281, wherein the composition is formulated as a solid dispersion.

285. The use according to any one of claims 189-284, wherein the composition is formulated as lipid nanoparticles, amorphous solid dispersions, lipid polymers, or combinations thereof.

286. The use according to any one of claims 189-285, wherein the composition is formulated as a supplement.

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