Compositions and methods for light-activated therapeutic or cosmetic treatment

Abstract

Provided herein are compositions for providing or amplifying a therapeutic or cosmetic benefit to a subject. Application of a composition comprising a photoactive agent to an external area of the subject in combination with irradiation of the external area with visible or near-visible light, induces a photochemical reaction in the photoactive agent that provides or amplifies the therapeutic or cosmetic benefit. Certain compositions can be directed to specific tissues or cells or organelles in the subject. The beneficial light-responsive agents include but are not limited to agents with light-triggered therapeutic or cosmetic properties. Also provided herein are related methods of use of the composition for providing benefits to a subject, including but not limited to the skin, hair, and / or nails of the subject.

Description

COMPOSITIONS AND METHODS FORLIGHT-ACTIVATED THERAPEUTIC OR COSMETIC TREATMENTCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of under 35 U. S. C. § 119(e) of prior U. S.Provisional Application Serial No. 63 / 725,741. filed November 27, 2024, the entire content of which is incorporated herein.FIELD

[0002] The disclosed concept relates generally to compositions for providing a therapeutic or cosmetic benefit to a subject, or amplifying an existing therapeutic or cosmetic benefit, and more specifically, to compositions comprising a photoactive agent and methods for inducing a therapeutic effect by applying the composition to an external area of the subject and irradiating the external area with visible or near-visible light.BACKGROUND

[0003] Many agents with therapeutic and cosmetic benefits have been incorporated into compositions for application to the skin, and other external areas of the body, including but not limited to hair, hair follicles, nails, and nail beds. These agents have been both isolated from natural products and developed in the laboratory. The range of benefits is broad, and for some of these agents, both therapeutic and cosmetic value can be identified.

[0004] Certain agents used in care compositions for the skin and other external areas of the body are photoactive, that is, they interact with light. For example, both compounds that absorb and reflect light, i.e., pigments, and compounds that emit light, i.e., phosphors, can alter the apparent hue and color of skin and hair. As a further example, UV-absorbing pigments in sunscreens can provide both therapeutic and cosmetic value, in that they can both maintain the appearance and texture of skin over time and can reduce the risk of skin cancer.

[0005] Light can be applied intentionally to the surface of exterior areas of the body, including the skin. As example, photodynamic therapy exposed skin that has been pre-treated with a composition containing a photoactive agent, i.e.. a photosensitizer, to light of specific wavelengths. The light-activated photosensitizer generates reactive oxygen species that selectively destroy targeted cells or tissues, i.e., inert agent(s) in the skin are converted to active agent(s) through the action of light.1#124545638vlAttorney Docket No. 500187-00015 PATENT

[0006] Photoactive agents used in therapeutic and cosmetic compositions often exhibit performance that depends on the local environment in which they are activated. Their activity can vary based on factors such as tissue type, cellular context, or subcellular location. Thus, when these photoactive agents are applied topically, only a portion of the applied material may reach conditions suitable for optimal activation, and thus produce a desired effect. As a result, relatively high amounts of a photoactive agent may be required to achieve a meaningful effect. This can lead to inefficient use of the active ingredient, increased cost of treatment, and potential concerns associated with overexposure either to the photoactive agent or to the light source. This latter effect can reduce or completely eliminate the appeal of the composition to a consumer.

[0007] For these reasons, there remains a need for improved compositions and related methods that enhance the effectiveness of light-responsive agents, in particular those that can provide a therapeutic or cosmetic benefit under ambient light or intentionally applied light. Such improvements would allow more reliable activation, reduced usage levels, and an overall more efficient and appealing product for consumers.SUMMARY

[0008] These needs, and others, are met by providing novel compositions comprising a photoactive agent. The composition may be applied topically to an external area of a subject, including but not limited to skin, wherein the composition is configured to deliver the photoactive agent to an intended tissue or cell or organelle. After topical application of the composition, the external area of the subject may be irradiated with visible or near- visible light. The photoactive agent, having been delivered to its desired site, undergoes a photochemical transformation at that site which provides a therapeutic or cosmetic benefit to the subject. Alternatively, the photochemical transformation amplifies an existing therapeutic or cosmetic benefit that is provided by the photoactive agent to the subject.

[0009] The photoactive agent may comprise a chromophore, such as a porphyrin from a plant, marine, aquatic, or animal source; a vitamin or derivative thereof; a natural product or extract from algae, plankton, seaweed, Tetraselmis, Chlorella, Spirulina, Ulva, Dunaliella, Fucus, Laminaria, Chondrus, Lindera, Camellia (such as green tea, black tea, white tea), Silybum (such as silymarin), Aspalathus (such as rooibos), Glycyrrhiza (such as licorice), Curcuma (such as curcumin), Frangula (such as coffeeberry), Vitis (such as grape, grape seeds); a mineral or derivative thereof; or any combination thereof.

[0010] #124545638vl 2Attorney Docket No. 500187-00015 PATENTDETAILED DESCRIPTION

[0011] Provided herein is a composition comprising a photoactive agent, wherein the photoactive agent, after topical application of the composition to an external area of a subject, followed by irradiation of the external area of the subject with visible or near-visible light, undergoes a photochemical transformation that provides or amplifies a therapeutic or cosmetic benefit to the subject. Also provided herein are methods of use of the disclosed compositions.

[0012] The compositions and methods disclosed herein are distinct from those of photodynamic therapy. In that therapeutic technique, a photosensitizer is delivered to a desired target in the body, typically a tumor, and irradiation of the photosensitizer generates reactive oxygen species, which in turn attack the target and cause necrosis.

[0013] In contrast, the compositions and methods disclosed herein are intended to provide a direct benefit to the irradiated area. This is not to be confused with an indirect benefit to a subject that might be provided by destruction of potentially life-threatening tumors. Rather, the photochemical cascade initiated through use of compositions and methods disclosed herein will provide a positive effect in the area at or surrounding the photoactive agent.

[0014] In the same vein, the compositions and methods disclosed herein should be distinguished from sunscreens and their use to prevent against the damaging effect of solar irradiation.Sunscreens generally do not provide meaningful selectivity towards a target tissue or cell or organelle. More importantly, the photochemical “reaction” of sunscreens is simply absorption of otherwise damaging solar radiation, generally in the near-UV portion of the spectrum. In contrast, this disclosure contemplates photochemical reactions that extend beyond solely absorption and absorption / emission (i.e., fluorescence and phosphorescence). It will again be appreciated that, although a subject will no doubt benefit from protection of UV irradiation due to absorption by a sunscreen, the sunscreen cannot properly be considered as a photoactive agent that is transformed chemically and / or physically, upon irradiation, to a beneficial species.

[0015] In some embodiments, the disclosed compositions comprise an agent that is capable of directing the photoactive agent to a particular tissue or cell or organelle. In some embodiments, the composition comprises an agent that is covalently or non-covalently linked to the photoactive agent, and which directs the agent to a particular tissue or cell or organelle. In some embodiments, the composition comprises a microcapsule which can selectively release the photoactive agent at a particular tissue or cell or organelle.#124545638vl 3Attorney Docket No. 500187-00015 PATENT

[0016] In some embodiments, the contents of the microcapsule are released into the cytoplasm of the cell. As a result of this selectivity, for a given dosage of photoactive agent, a higher concentration of the agent will eventually be located in the tissue or cell or organelle.

[0017] The advantages of delivery of a photoactive agent, with the compositions and methods outlined herein, will be apparent. For delivery of a certain amount of agent to the intended tissue or cell or organelle, the selectivity can allow for application of a smaller dosage of agent to an external area of the subject than otherwise would be needed, providing both cost and safety benefits.Likewise, accumulation of the agent in the intended tissue or cell or organelle can decrease either the intensity or duration of light irradiation necessary to achieve an intended effect, thereby minimizing unnecessary and potentially hazardous overexposure to light.

[0018] In some embodiments, the external area of the subject may be chosen from skin, hair, hair follicles, nail, and nail beds. In some embodiments, the photoactive agent is topically applied to the skin.

[0019] In some embodiments, the photoactive agent provides, on irradiation with light, a therapeutic or cosmetic benefit to the subject. In some embodiments, irradiation of the photoactive agent with light amplifies an existing therapeutic or cosmetic benefit to the subject.

[0020] In some embodiments, the photoactive agent can undergo a photochemical reaction, on irradiation with light, which produces or transforms into an agent that is capable of providing or amplifying a therapeutic or cosmetic benefit to the subj ect. In some embodiments, the photochemical reaction is a cleavage reaction. In some embodiments, the photochemical reaction is a rearrangement reaction. In some embodiments, the photochemical reaction is an isomerization reaction.

[0021] In some embodiments, the photoactive agent comprises a chromophore. In some embodiments, the photoactive agent comprises a polycyclic chromophore. In some embodiments, the photoactive agent comprises a porphyrin.

[0022] In some embodiments, the photoactive agent comprises a naturally occurring chromophore. In some embodiments, the photoactive agent comprises a plant chromophore. In some embodiments, the photoactive agent comprises a chromophore from a marine or aquatic or algal source.

[0023] In some embodiments, the photoactive agent is a natural product. In some embodiments, the photoactive agent is an extract from a natural product. In some embodiments, the natural product is chosen from algae, plankton, seaweed, Tetraselmis, Chlorella, Spirulina, Ulva, Dunaliella, Fucus, #124545638vl 4Attorney Docket No. 500187-00015 PATENTLaminaria, Chondrus, Lindera, Camellia (such as green tea, black tea, white tea), Silybum (such as silymarin), Aspalathus (such as rooibos), Glycyrrhiza (such as licorice), Curcuma (such as curcumin), Frangula (such as coffeeberry), Vitis (such as grape, grape seeds).

[0024] In some embodiments, the photoactive agent is an antioxidant or a skin conditioning agent. In some embodiments, the antioxidant or skin conditioning agent is chosen from vitamin A and derivatives thereof, including retinol, retinyl palmitate, retinyl acetate, retinyl retinoate retinyl propionate, retinyl linoleate and retinaldehyde; vitamin B and derivatives thereof, including niacin and niacinamide; vitamin C and derivatives thereof, including ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, ascorbyl tetraisopalmitate, ascorbyl methylsilanol pectinate, tetrahexyldecyl ascorbate, aminopropyl ascorbyl phosphate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate; vitamin E and derivatives thereof, including tocopherol, tocopheryl linoleate and tocopheryl acetate; or other skin conditioning agents such as resveratrol, ubiquinone, ubiquinol. hydroxydecyl ubiquinone, ferulic acid, glutathione, polyphenols, beta carotene, zinc, and quercetin.

[0025] In some embodiments, the photoactive agent comprises a mineral agent. Exemplary mineral agents comprise magnesium, such as the magnesium ascorbyl phosphate (MAP) mentioned above, magnesium salt of pyrrolidone carboxylic acid (Mg PCA), magnesium sulfate, magnesium chloride, magnesium hydroxide, magnesium stearate, magnesium gluconate, magnesium lactate, or magnesium porphyrins; hematite; copper such as copper oxide, cuprous oxide, or copper peptide; gold or silver nanoparticles; and the like.

[0026] In some embodiments, the photoactive agent comprises an algae extract, a vitamin or derivative thereof, a mineral agent, or any combination thereof. In some embodiments, the vitamin or derivative thereof is vitamin C or a derivative of vitamin C, the algae extract comprises an extract from spirulina, and the mineral agent comprises magnesium PCA, magnesium sulfate, or a combination thereof.

[0027] In some embodiments, the photoactive agent comprises magnesium ascorbyl phosphate, magnesium salt of pyrrolidone carboxylic acid, sodium ascorbyl phosphate, an extract of spirulina, such as an extract of Spirulina platensis, or any combination thereof.

[0028] In some embodiments, the photoactive agent comprises a combination of an extract of Spirulina platensis with one or more of MAP, Mg PCA, or sodium ascorbyl phosphate (SAP).

[0029] In some embodiments, the photoactive agent may be included in the disclosed compositions at from 0.001 % by weight, such as 0.005, 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 15, 20, 30, 40, 50, 60, 70, 80, or even 90 % by weight photoactive agent, and up to 99.9 % by weight, such as up#124545638vl 5Attorney Docket No. 500187-00015 PATENTto 90, 80, 70, 60, 50, 40, 30, 20, 18, 16, 14, 12, 10, 8, or 6 % by weight photoactive agent, based on the total weight of the composition. Any combination of upper and lower amount of the photoactive agent may define a possible range and is within the scope of the disclosed composition, such as 0.001 % to 99.9 % by weight, or 0.01 to 50.0 % by weight, or 0.01 to 25.0 % by weight, or 0.01 to 10 %, or 0.001 % to 15.0 % by weight, 0.1 % to 5.0 % by weight, or 1.0 % to 5.0 % by weight, or 0.1 % to 10 % by weight, based on the total weight of the composition.

[0030] In some embodiments, when more than one photoactive agent is included in the disclosed composition, each photoactive agent may be individually included in the disclosed compositions in any amount so that the total photoactive agent in the composition comprises from 0.001 % by weight, such as 0.005, 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 15, 20, 30, 40, 50, 60, 70, 80, or even 90 % by weight photoactive agent(s), and up to 99.9 % by weight, such as up to 90, 80, 70, 60, 50, 40, 30. 20. 18, 16, 14, 12, 10, 8. or 6 % by weight photoactive agent(s), based on the total weight of the composition. As above, any combination of upper and lower amount of the photoactive agents may define a possible range and is within the scope of the disclosed composition, such as 0.001 % to 25.0 % by weight, or 0.01 % to 5.0 % by weight, or 0.1 % to 10 % by weight, based on the total weight of the composition.

[0031] In some embodiments, the photoactive agent comprises a combination of spirulina, Mg PCA, and / or MAP. In some embodiments, the photoactive agent comprises a ratio of spirulina to Mg PCA + MAP of 200:0 to 0:200. such as 200:1 to 1:200, or 100:1 to 1:100. or 50:1 to 1:50, or 40:1 to 1:40, or 20:1 to 1:20, or 10: 1 to 1:10, or 5:1 to 1:5, or 2:1 to 1:2, or 1:1 (spirulina: (Mg PCA + MAP)). In some embodiments, the Mg PCA + MAP may be provided in the combination of spirulina, Mg PCA, and MAP in a ratio of 200:0 to 0:200, such as 200: 1 to 1:200, or 100: 1 to 1:100. or 50:1 to 1:50, or 40:1 to 1:40, or 20:1 to 1:20, or 10:1 to 1:10. or 5:1 to 1:5. or 2:1 to 1:2. or 1:1, or 1:0, or 0:1 (Mg PCA: MAP).

[0032] In some embodiments, the therapeutic or cosmetic benefit is a cosmetic benefit.

[0033] In some embodiments, the cosmetic benefit is a cosmetic improvement of the skin.

[0034] In some embodiments, the cosmetic improvement of the skin consists of an improvement in the plumpness, firmness, elasticity, or tightness of the skin.

[0035] In some embodiments, the cosmetic improvement of the skin is a cosmetic improvement of the texture of the skin. In some embodiments, the cosmetic improvement of the texture of the skin consists of a reduction in appearance or size of pores.#124545638vl 6Attorney Docket No. 500187-00015 PATENT

[0036] In some embodiments, the cosmetic improvement of the skin consists of a reduction in puffiness or inflammation of the skin.

[0037] In some embodiments, the cosmetic improvement of the skin consists of an improvement in the appearance of lines in the skin. In some embodiments, the improvement in the appearance of lines in the skin is chosen from reduced visual prominence of the lines, reduced length, width or depth of the lines, and reduced size or volume of the lines. In some embodiments, the lines in the skin are chosen from fine lines, crow’s feet, frown lines, forehead lines, and perioral smile lines. In some embodiments, the lines in the skin are chosen from lines on the chest and / or neck (e.g., decolletage), back of hands, and other regions of the body such as legs, arms, and the like.

[0038] In some embodiments, the cosmetic improvement of the skin consists of an improvement in the appearance of wrinkles in the skin. In some embodiments, the improvement in the appearance of wrinkles in the skin is chosen from reduced number, reduced width, reduced depth, and reduced visual prominence.

[0039] In some embodiments, the cosmetic improvement of the skin consists of an improvement in the overall visual appearance of the skin. In some embodiments, the improvement in the overall visual appearance of the skin is increased uniformity of skin tone. In some embodiments, the improvement in the overall visual appearance of the skin is chosen from improved skin brightness, luminosity, radiance, youthfulness, and glow. In some embodiments, the improvement in the overall visual appearance of the skin is decreased redness.

[0040] In some embodiments, the cosmetic improvement of the skin consists of an improvement in the visual appearance of a localized disfigurement to the skin. In some embodiments, the improvement in the visual appearance of a localized disfigurement to the skin is a reduction in the number, size, or visual prominence of the disfigurement to the skin. In some embodiments, the localized disfigurement to the skin is chosen from dark spots, blemishes, and hyperpigmented regions. In some embodiments, the localized disfigurement to the skin is chosen from a subocular, periocular, manual, and podiatric disfigurement. In some embodiments, the localized disfigurement to the skin is caused or exacerbated by excessive exposure to intense irradiation in the visible or ultraviolet spectrum. In some embodiments, the intense irradiation in the visible or ultraviolet spectrum is sunlight.

[0041] In some embodiments, the therapeutic or cosmetic benefit is a therapeutic benefit. In some embodiments, the therapeutic benefit is a therapeutic benefit to the skin. In some embodiments, the therapeutic benefit to the skin consists of decreased sensitivity, irritation, or pruritus. In some#124545638vl 7Attorney Docket No. 500187-00015 PATENTembodiments, the therapeutic benefit to the skin consists of decreased susceptibility to a dermatological disease. In some embodiments, the dermatological disease is chosen from dermatitis and skin cancer. In some embodiments, the therapeutic benefit to the skin consists of decreased susceptibility to excessive exposure to intense irradiation in the visible or ultraviolet spectrum. In some embodiments, the intense irradiation in the visible or ultraviolet spectrum is sunlight.

[0042] In some embodiments, the cosmetic or therapeutic benefit is chosen from reduced hair loss, increased hair growth, reduced dandruff, reduced seborrheic dermatitis, reduced psoriasis, reduced contact dermatitis, reduced folliculitis, or any combination thereof.

[0043] In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with visible light. In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with red light. In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with near-infrared light.

[0044] In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with light having a wavelength between 870-890 nm, inclusive.

[0045] In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with light having a wavelength between 750-870 nm, inclusive, optionally between 820-840 nm, inclusive.

[0046] In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with light having a wavelength between 650-670 nm, inclusive.

[0047] In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with light having a wavelength between 595-615 nm, inclusive.

[0048] In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with light having a wavelength between 575-675 nm, inclusive, optionally between 620-640 nm, inclusive.

[0049] In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with light having a wavelength between 490-580 nm, inclusive, optionally between 515-550 nm, inclusive.

[0050] In some embodiments, the therapeutic or cosmetic benefit is provided upon irradiation with light having a wavelength between 405-425 nm, inclusive.

[0051] In some embodiments, the therapeutic or cosmetic benefit is chosen from wound healing, stimulation of production of skin proteins such as collagen and elastin, protection of such proteins, #124545638vl 8Attorney Docket No. 500187-00015 PATENTalteration of mitochondrial function, alteration of ATP production, alteration of metabolic activity, and decrease in the amount of oxidizing species.

[0052] In some embodiments, the photoactive agent is provided in a delivery system such as a liposome or a microvesicle or a microcapsule. In some embodiments, the delivery system comprises a polymeric shell. In some embodiments, the delivery system comprises exosomes. In some embodiments, the delivery system comprises a nanoemulsion.

[0053] In some embodiments, the delivery system comprises nano- or microparticles, i.e., microcapsules, formed of biocompatible materials, such as lipids. Lipid-based microcapsules such as liposomes and lipid microcapsules can encapsulate both hydrophilic and hydrophobic agents.

[0054] In some embodiments, the delivery system comprises a liposome comprising an aqueous interior configured to encapsulate the photoactive agents. Suitable liposomes include multilamellar vesicles, small unilamellar vesicles, and large unilamellar vesicles, each of which can be formed from biocompatible phospholipids, for example phosphatidylcholine. In certain embodiments, the liposomes promote improved penetration, stability, and controlled release of the encapsulated photoactive agent(s).

[0055] In some embodiments, the delivery system comprises microcapsules formed of poly(lactic-co-glycolic acid) (PLGA), which is biocompatible and biodegradable. PLGA provides encapsulation of a variety of substances both hydrophilic and hydrophobic and with sizes ranging from small molecules to macromolecules, and delivery at various targeted locations through transdermal delivery. The ratio of lactic acid to glycolic acid in the PLGA polymer may be tuned to adjust the properties and degradation rate of the polymer. As such, encapsulation of the photoactive agents disclosed herein within PLGA microcapsules provides sustained and delayed release options for delivery of the photoactive agents deep into the skin.

[0056] In some embodiments, the delivery system comprises microcapsules formed of polyethylene glycol (PEG), chitosan, hyaluronic acid, alginate, collagen, gelatin, starch, pectin, carrageenan, xanthan gum, guar gum, polylactic acid (PLA), and / or poly caprolactone (PCL).

[0057] In some embodiments, the delivery system comprises microcapsules that are stimuli-responsive nanomaterials, such as materials that alter their shape in reaction to pH, temperature, and enzyme activity. The encapsulated photoactive agent may be released as a result of these structural alterations, enabling localization of the photoactive agent. Exemplary nanomaterials that respond to body temperatures include at least the block copolymer poly(ethylene oxide)a-poly(propylene oxide)b-poly(ethylene oxide)a (PEO-PPO-PEO); poly(oligo(ethylene glycol)#124545638vl 9Attorney Docket No. 500187-00015 PATENTmethacrylate-co-poly(glycidyl methacrylate) copolymers (P(OEGMA-co-PGMA)); collagen-based and chitosan-based polymers; and poly(N-isopropylacrylamide)-poly(N. N-dimethylacrylamide)-poly(acrylic acid) (PNIPAM-PDMA-PAA).

[0058] In some embodiments, the delivery system, e.g., liposome or microvesicle or microcapsule, includes one or more surface bound targeting agents configured to direct the delivery system to a specific tissue, cell, or organelle type. Such targeting agents may include antibodies, antibody fragments, peptides, ligands, carbohydrates, aptamers, or other receptor-binding molecules capable of selectively associating with markers expressed on the target tissues, cells, or organelles.Functionalization of the delivery system exterior in this manner enables enhanced localization, binding, and uptake of the encapsulated photoactive agents by the intended tissue or cell or organelle.

[0059] In some embodiments, the delivery system is internalized by a target tissue or cell or organelle. In some embodiments, the target cell is an epidermal cell. In some embodiments, the target cell is a non-epidermal cell. In some embodiments, the delivery system can penetrate at least one skin layer. In other aspects, the delivery system can penetrate the cornified layer (stratum comeum), translucent layer (stratum lucidum), granular layer (stratum granulosum), spinous layer (stratum spinosum), or basal / germinal layer (stratum basal / germinativum).

[0060] In some embodiments, the photoactive agent is included in the delivery system at 0.01 to 99.9 % by weight, such as 0.1 to 90 % by weight, 0.1 to 80 % by weight, 0.1 to 70 % by weight, 0.1 to 60 % by weight, 0.1 to 50 % by weight, 0.1 to 40 % by weight, 0.1 to 30 % by weight, 0.1 to 20 % by weight, or 0.01 to 10 % by weight, or 0.1 to 8 % by weight, or 1 to 6 % by weight, or 1 to 5% by weight, or 1 to 4 % by weight, or 1 to 3 % by weight, or 1 to 2 % by weight, based on the total weight of the delivery system comprising the photoactive agent.

[0061] In some embodiments, the delivery system comprises at least 1 % by weight, such as at least 2, 3, 4, 5, 6, 7, 8, or 9 % by weight of the photoactive agent, based on the total weight of the delivery system comprising the photoactive agent. In some embodiments, the delivery system comprises at least 10 % by weight, such as at least 20, 30, 40, 50, 60, 70, 80, or 90 % by weight of the photoactive agent, based on the total weight of the delivery system comprising the photoactive agent. In some embodiments, the delivery system comprises not more than 10 % by weight, such as not more than 9, 8, 7, 6. 5, 4, 3, or 2 % by weight of the photoactive agent, based on the total weight of the delivery system comprising the photoactive agent. In some embodiments, the delivery system comprises not more than 99.9 % by' weight, such as not more than 90, 80, 70, 60, 50, 40, 30,#124545638vl 10Attorney Docket No. 500187-00015 PATENTor 20 % by weight of the photoactive agent, based on the total weight of the delivery system comprising the photoactive agent. The delivery system may comprise the photoactive agent in a range defined by any combination of the noted upper and lower amounts.

[0062] As an example, the photoactive agent may be included in the delivery system, e.g., liposome, at 3% by weight, based on the total weight of the delivery system comprising the photoactive agent. The photoactive agent may comprise spirulina: Mg PCA: MAP from 3%: 0%: 0% to 1%: 1%: 1%, based on the total weight of the delivery system comprising the photoactive agent. As another example, the photoactive agent may comprise spirulina: (Mg PCA + MAP) at from 3%: 0% to 1%: 2 %, based on the total weight of the delivery system comprising the photoactive agent, wherein the ratio of Mg PCA to MAP can range between 100:0 to 0: 100, such as 80:1 to 1:80.

[0063] As another example, the photoactive agent may be included in the delivery system at 4 % total, based on the total weight of the delivery system comprising the photoactive agent. Thus, the photoactive agent may comprise spirulina: Mg PCA: MAP at from 4%: 0%: 0% to 1.33%: 1.33%: 1.33%, based on the total weight of the delivery system comprising the photoactive agent, or the photoactive agent may comprise spirulina: (Mg PCA + MAP) at from 4%: 0% to 1.33%: 2.67 %, based on the total weight of the delivery system comprising the photoactive agent, wherein the ratio of Mg PCA to MAP can range between 100:0 to 0:100, such as 80:1 to 1:80.

[0064] As yet another example, the photoactive agent may be included in the delivery system at 5 % total, based on the total weight of the delivery system comprising the photoactive agent. Thus, the photoactive agent may comprise spirulina: Mg PCA: MAP at from 5%: 0%: 0% to 1.66%: 1.66%: 1.66%, based on the total weight of the delivery system comprising the photoactive agent, or the photoactive agent may comprise spirulina: (Mg PCA + MAP) at from 5%: 0% to 1.66%: 3.33 %, based on the total weight of the delivery system comprising the photoactive agent, wherein the ratio of Mg PCA to MAP can range between 100:0 to 0:100, such as 80:1 to 1:80.

[0065] As yet another example, the photoactive agent may be included in the delivery system at 10 % total, based on the total weight of the delivery system comprising the photoactive agent. Thus, the photoactive agent may comprise spirulina: Mg PCA: MAP at from 10%: 0%: 0% to 3.33%: 3.33%: 3.33%, based on the total weight of the delivery system comprising the photoactive agent, or the photoactive agent may comprise spirulina: (Mg PCA + MAP) at from 10%: 0% to 3.33%: 6.66%, based on the total weight of the delivery system comprising the#124545638vl 11Attorney Docket No. 500187-00015 PATENTphotoactive agent, wherein the ratio of Mg PC A to MAP can range between 100: 0 to 0: 100. such as 80:1 to 1:80.

[0066] In some embodiments, the delivery system comprising the photoactive agent is included in the composition at 0.01 to 99.9 % by weight, such as 0.01 to 90 % by weight, or 0.01 to 75 % by weight, or 0.01 to 50 % by weight, or 0.01 to 25 % by weight, or 0.1 to 15 % by weight, or 0.1 to 10 % by weight, or 1 to 10 % by weight, or 1 to 5 % by weight, based on the total weight of the delivery system comprising the photoactive agent. In some embodiments, the composition comprises at least 0.01 % by weight of the delivery system comprising the photoactive agent, such as at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or at least 20 % by weight. In some embodiments, the composition comprises not more than 25 % by weight of the delivery system comprising the photoactive agent, such as not more than 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12. 11. 10, 9, 8, 7, 6, 5 % by weight. In some embodiments, the composition comprises at least 0.01 % by weight of the delivery system comprising the photoactive agent, such as 0.005, 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 15, 20, 30, 40, 50, 60, 70, 80, or even 90 % by weight, and up to 99.9 % by weight, such as up to 90, 80, 70, 60, 50, 40, 30, 20, 18, 16, 14, 12, 10, 8, or 6 % by weight, based on the total weight of the composition. The composition may comprise the delivery system comprising the photoactive agent in a range defined by any combination of the noted upper and lower amounts, such as 0.001 % to 99.9 % by weight, or 0.01 to 50.0 % by weight, or 0.01 to 25.0 % by weight, or 0.01 to 10 %, or 0.001 % to 15.0 % by weight, 0.1 % to 5.0 % by weight, or 1.0 % to 5.0 % by weight, or 0.1 % to 10 % by weight, based on the total weight of the composition.

[0067] In some embodiments, the average size of the delivery system or microcapsule, as determined by dynamic light scattering or scanning electron microscopy (SEM), is between 10 nm and 10 pm, inclusive, optionally between 20 nm and 1.5 pm, inclusive, optionally between 100 to 500 nm, inclusive, optionally between 150 to 600 nm, inclusive, optionally between 180 to 400 nm, inclusive, optionally between 150 to 300 nm, inclusive.

[0068] In some embodiments, the average size of the delivery system or microcapsule, as determined by dynamic light scattering or scanning electron microscopy (SEM), is at least 10 nm, such as at least 20 nm, of at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or at least 250 nm, or at least 300 nm, or at least 400 nm, or at least 500 nm. In some embodiments, the average size of the delivery system or microcapsule, as determined by dynamic light scattering or scanning electron microscopy (SEM), is less than 10 pm, such as less than 8 pm, or less than 6 pm, or less than 4 pm, or less than 2 pm, or less than 1 pm, or less than 0.8 pm, or less than 0.6 pm. #124545638vl 12Attorney Docket No. 500187-00015 PATENTAny combination of upper and lower size of the microcapsules is possible and within the scope of the disclosed composition.

[0069] In some embodiments, the composition comprises an emollient. Exemplary emollients include isopropyl myristate, petrolatum, volatile or non-volatile silicones oils (e.g., methicone, dimethicone), ester oils, mineral oils, rosehip oil, shea butter, jojoba oil, castor oil, macadamia oil, argan oil, kukui nut oil, petrolatum, mineral oil, evening primrose oil and fatty acid esters. The composition may comprise from 0.01 % by weight, such as from 0.1 %, 0.5 %, 1 %, 3 %, 5 %, 10 % by weight, up to 20 % by weight, such as to up to 18 %. 15 %, 12 %, 10 %. 9 %, 8 %, 7 %, 6 %, 5 %, or 4 % by weight emollient, based on the total weight of the composition. Any combination of upper and lower amount of the emollient may define a possible range and is within the scope of the disclosed composition.

[0070] In some embodiments, the composition comprises a photosensitizer. As used herein, “photosensitizer” preferably means a chemical compound that, absorbs light and confers the energy from light absorption to another species. Non-limiting examples of photosensitizers include aminolevulinic acid esters, porphyrins, porphyrin derivatives, bacteriochlorins, isobacteriochlorins, phthalocyanine, naphthalocyanines, pyropheophorbides, sapphyrins, texaphyrins, tetrahydrochlorins, purpurins, porphycenes, phenothiaziniums, and metal complexes such as, but not limited to, tin, aluminum, zinc, lutetium, and tin ethyl etiopurpurin (SnET2), and combinations thereof. The composition may comprise from 0.01 % by weight, such as from 0.1 %, 0.5 %. 1 %, 3 %, 5 %, 10 % by weight, up to 20 % by weight, such as to up to 18 %, 15 %, 12 %, 10 %, 9 %, 8 %, 7 %, 6 %, 5 %, or 4 % by weight photosensitizer, based on the total weight of the composition. Any combination of upper and lower amount of the photosensitizer may define a possible range and is within the scope of the disclosed composition.

[0071] In some embodiments, the composition comprises a dermatologically acceptable or pharmaceutically acceptable carrier. Generally, the composition may be suitable for topical administration to the skin of a subject, such that the photoactive agent is present in an effective amount. The term “dermatologically acceptable carrier” refers to carriers suitable for use in the therapeutic and / or cosmetic compositions disclosed herein that should be safe for use in contact with human skin tissue. Suitable carriers can include water and / or water miscible solvents. The therapeutic and cosmetic compositions disclosed herein can comprise from 1 to 95 wt. % water and / or water miscible solvent. The composition may comprise from 1 %, 3 %, 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, 50 %, 55 %, 60 %, 65 %, 70 %, 75 %, 80 %, or 85 % to about 90 %, 85 %, 80 %, 75 %, 70 %, 65 %, 60 %, 55 %, 50 %, 45 %, 40 %, 35 %, 30 %, 25 %, 20 %, 15 #124545638vl 13Attorney Docket No. 500187-00015 PATENT%, 10 %, or 5 % by weight water and / or water miscible solvents, based on the total weight of the composition. Any combination of upper and lower amount of the carrier may define a possible range and is within the scope of the disclosed composition. Suitable water miscible solvents include monohydric alcohols, dihydric alcohols, polyhydric alcohols, glycerol, glycols, polyalkylene glycols such as polyethylene glycol, and mixtures thereof.

[0072] Suitable carriers may also include oil(s). The compositions disclosed herein can comprise from 1 % to 95 % by weight of one or more oils. The compositions may comprise from 0.1 %, 0.5 %. 1 %, 2 %, 5 %, 10 %, 15 %, 20 %, 25 %, 30 %, 35 %, 40 %, 45 %, 50 %, 55 %, 60 %, 65 %, 70 %, 75 %, 80 %, 85 %, or 90 % to about 90 %, 85 %, 80 %, 75 %, 70 %, 65 %, 60 %, 55 %, 50 %, 45 %, 40 %, 35 %, 30 %, 25 %, 20 %, 15 %, 10 %, 5 %, or 3 % by weight of one or more oils, based on the total weight of the composition. Any combination of upper and lower amount of the oil(s) may define a possible range and is within the scope of the disclosed composition.

[0073] Oils may be used to solubilize, disperse, or carry materials that are not suitable for water or water soluble solvents. Suitable oils may include silicones, hydrocarbons, esters, amides, ethers, and mixtures thereof. The oils may be volatile or nonvolatile. Suitable silicone oils also include poly siloxanes. Commercially available polysiloxanes include the polydimethylsiloxanes, which are also known as dimethicones.

[0074] Suitable hydrocarbon oils may include straight, branched, or cyclic alkanes and alkenes. The chain length may be selected based on desired functional characteristics such as volatility. Suitable volatile hydrocarbons may have between 5-20 carbon atoms or. alternately, between 8-16 carbon atoms. Other suitable oils include esters. The suitable esters typically contained at least 10 carbon atoms. These esters include esters with hydrocarbyl chains derived from fatty acids or alcohols (e.g., mono-esters, polyhydric alcohol esters, and di- and tri-carboxylic acid esters). The hydrocarbyl radicals of the esters hereof may include or have covalently bonded thereto other compatible functionalities, such as amides and alkoxy moieties (e.g., ethoxy or ether linkages, etc.).

[0075] Other suitable oils include amides. Amides include compounds having an amide functional group while being liquid at 25° C. and insoluble in water. Suitable amides include N-acetyl-N-butylaminopropionate, isopropyl N-lauroylsarcosinate, and N, N-diethyltoluamide. Other suitable oils include ethers. Suitable ethers include saturated and unsaturated fatty ethers of a polyhydric alcohol, and alkoxylated derivatives thereof.

[0076] In some embodiments, the composition comprises a surfactant. Exemplary surfactants may enable disruption of the epidermal skin barrier, emulsify sebum, improve mixing of hydrophilic#124545638vl 14Attorney Docket No. 500187-00015 PATENTparticles (microcapsules of the delivery system) with hydrophobic solutions, and reduce entropic barriers to delivering hydrophilic particles to hydrophobic regions of the skin (e.g., between the hair shaft and surrounding sheath or follicle). Exemplary surfactants include at least sodium dodecyl sulfate, sodium laureth 2-sulfate, ammonium lauryl sulfate, sodium octech-l / deceth-1 sulfate, and the like, which may be included at 0.01 to 10 % by weight based on the total weight of the composition. For example, surfactants may be included in the composition at 0.1 % by weight or more, or at least 0.5 %, 1.0 %, 2.0 %, 4.0 %, 6.0 %, or at least 8.0 % by weight, based on the total weight of the composition. Surfactants may be included in the composition at not more than 10 % by weight, such as less than 8 %, 6 %, 4 %, 2 %, or less than 1 % by weight, based on the total weight of the composition. Any combination of upper and lower amount of the surfactant may define a possible range and is within the scope of the disclosed composition.

[0077] In some embodiments, the composition comprises an emulsifier. An emulsifier is particularly suitable when the composition is in the form of an emulsion or if immiscible materials are being combined. The compositions may comprise from 0.05 % by weight, such as 0.1 %, 0.2 %, 0.3 %, 0.5 %, 1 %, 2 %, 4 %, 6 %, 8 % by weight, and up to 20 %, 10 %, 5 %, 3 %, 2 %, or 1 % by weight emulsifier. Any combination of upper and lower amount of the emulsifier may define a possible range and is within the scope of the disclosed composition. Emulsifiers may be nonionic, anionic, or cationic.

[0078] In some embodiments, the composition comprises a structuring agent, which may be used to increase viscosity, thicken, solidify, or provide solid or crystalline structure to the composition. Structuring agents are typically grouped based on solubility, dispersability, or phase compatibility. Examples of aqueous or water structuring agents include polymeric agents, natural or synthetic gums, polysaccharides, and the like. In one aspect, the compositions may comprise from 0.0001 % by weight, such as from 0.001 %, 0.01 %, 0.05%, 0.1 %, 0.5 %, 1 %, 2 %, 3 %, 5 % and up to 25 % by weight, such as up to 2 0%, 10 %, 7 %, 5 %, 4 %, or 2 % by weight of the one or more structuring agents, based on the total weight of the composition. Any combination of upper and lower amount of the structuring agent may define a possible range and is within the scope of the disclosed composition.

[0079] In some embodiments, the compositions comprise a gelling agent. The term “gelling agent” refers to materials used to thicken and stabilize liquid solutions, emulsions, and suspensions. They dissolve in the liquid phase as a colloid mixture that forms an internal structure giving the resulting gel an appearance of a solid matter, while being mostly composed of a liquid. Gelling agents are similar to thickeners.#124545638vl 15Attorney Docket No. 500187-00015 PATENT

[0080] In some embodiments, the composition comprises a detectable colorant (e.g., a pigment).

[0081] In some embodiments, the composition comprises a detectable fragrance.

[0082] In some embodiments, the compositions disclosed herein may be prepared and / or administered, for example, as a solution, a gel, a cream, a lotion, an ointment, an emulsion, a suspension, a paste, an aerosol, an aerosol foam, an aerosol powder, a lotion, a liniment, an ointment, a tincture, a salve, a poultice, a spray, a dry power, or a combination thereof.

[0083] Also provided herein is a method for providing or amplifying a therapeutic or cosmetic benefit to a subject, the method comprising applying a composition as disclosed herein to an external area of the subject, and irradiating the external area of the subject with visible or near-visible light.

[0084] In some embodiments, the external area of the subject is chosen from skin, hair, hair follicles, nail, and nail beds. In some embodiments, the external area of the subject is skin.

[0085] In some embodiments, irradiation commences after application of the composition. In some embodiments, irradiation commences during or after application of the composition. In some embodiments, commencement of irradiation is concurrent with commencement of application of the composition. In some embodiments, irradiation commences before application of the composition.

[0086] Also provided herein is a method for providing or amplifying a therapeutic or cosmetic benefit to a subject, the method comprising applying a composition as disclosed herein to the skin of the subject, and irradiating the skin of the subject with visible or near- visible light.

[0087] In some embodiments, the method provides a therapeutic or cosmetic benefit to the subject. In some embodiments, the method amplifies an existing therapeutic or cosmetic benefit that is provided by the photoactive agent to the subject.

[0088] In some embodiments, irradiation is not sunlight. In some embodiments, irradiation is not sunlight or derived from sunlight. In some embodiments, the irradiation is provided by a nonnatural light source, including but not limited to a lamp, a laser, and a luminous device.

[0089] In some embodiments, irradiation is provided by a lamp. In some embodiments, the lamp is chosen from an incandescent lamp, a fluorescent lamp, and an LED lamp. In some embodiments, the lamp can be powered from conventional AC service. In some embodiments, the lamp can be powered from one or more batteries.#124545638vl 16Attorney Docket No. 500187-00015 PATENT

[0090] In some embodiments, irradiation is provided by a laser. In some embodiments, irradiation is provided by a laser diode. In some embodiments, the plurality of light emitting sources are lightemitting diodes (LED). In some embodiments, irradiation is provided by any combination of lasers, laser diodes, or LEDs.

[0091] In some embodiments, irradiation is provided by an electronic skin rejuvenating apparatus, such as disclosed in US. Patent Publication Nos. 2024 / 0399164 or 2023 / 0271003, the contents of which are incorporated in full herein.

[0092] In some embodiments, irradiation is provided by an apparatus comprising a plurality' of light emitting sources that emit a light therapy or a therapeutic light that any one or more of near-infrared light that is between 750 nm and 1400 nm, such as between about 7500 nm to 900 nm; red light between about 630 nm to about 670 nm, such as 630 nm, 650 nm, and / or 660 nm; amber light between 570 nm to 620 nm; and / or blue light between about 410 nm to about 465 nm, such as 415 nm, 440 nm, and 465 nm.

[0093] In some embodiments, irradiation is provided by an apparatus comprising a plurality of light emitting sources that emit a light therapy or a therapeutic light in both the red light energy and the blue light energy, which would produce a purple light energy. In some embodiments, the light therapy or a therapeutic light is emitted in both the red light energy, including one or more of a wavelength at 630 nm, 650 nm, and / or 660 nm, and the blue light energy', including one or more of a wavelength at 415 nm, 440 nm, and 465 nm. In some embodiments, the light therapy or a therapeutic light is emitted in both the near-infrared light energy and the red light energy, such as at wavelengths of about 630 nm red light and 830 nm near-infrared light. In some embodiments, the light therapy or a therapeutic light is emitted in the amber light energy', such as at a wavelength of 605 nm amber light, and in the red light energy, such as at wavelengths of 630 nm and 660 nm red light, and in the near-infrared light energy’, such as at a wavelength of 830 nm near-infrared light.

[0094] In some embodiments, irradiation is provided by an unpowered light source. In some embodiments, irradiation is provided by a luminous device. In some embodiments, the luminous device comprises a fluorescent or phosphorescent material. In some embodiments, the luminous device comprises a chemiluminescent material.

[0095] In some embodiments, the light source is incorporated into an article of manufacture. In some embodiments, the article of manufacture comprises a natural or synthetic fabric. In some embodiments, the article of manufacture is chosen from a mat, a pad, a blanket, and a bed linen. In some embodiments, the article of manufacture is a wearable device. In some embodiments, the#124545638vl 17Attorney Docket No. 500187-00015 PATENTarticle of manufacture emits a beam of light that can be directed by a user. In some embodiments, the article of manufacture is configured to be handheld. In some embodiments, the article of manufacture is chosen from a wand, a panel, a comb, a brush, and a massager. In some embodiments, the article of manufacture is configured to be freestanding. In some embodiments, the article of manufacture is configured to be positioned at tabletop height. In some embodiments, the article of manufacture is configured to be mounted on a wall or ceiling. In some embodiments, the article of manufacture is provided with a positionable, optionally articulated, mount.

[0096] In some embodiments, the light source is incorporated into a garment. In some embodiments, the garment is chosen from a glove, a hat, a wrap, a poncho, a shirt, a gown, a robe, a mask, and a stocking. In some embodiments, the light source is specifically incorporated into a face mask, a neck wrap or collar, a leg wrap, or an arm wrap.

[0097] In some embodiments, the light source is provided with an optical filter. In some embodiments, the optical filter is chosen from an absorptive filter, a dichroic filter, a shortpass filter, a longpass filter, and a bandpass filter. In some embodiments, the filter substantially blocks ultraviolet radiation.

[0098] In some embodiments, the light is within the combined visible and near-infrared region of the spectrum. In some embodiments, the light is visible light. In some embodiments, the light is red light. In some embodiments, the light is near-infrared light.

[0099] In some embodiments, the light has a wavelength of 750 nm or greater, optionally 760 nm or greater, optionally 770 nm or greater, optionally 780 nm or greater, optionally 790 nm or greater, optionally 800 nm or greater, optionally 810 nm or greater. In some embodiments, the light has a wavelength of 870 nm or less, optionally 860 nm or less, optionally 850 nm or less, optionally 840 or less.

[0100] In some embodiments, the light has a wavelength of 575 nm or greater, optionally 590 or greater, optionally 605 or greater. In some embodiments, the light has a wavelength of 675 nm or less, optionally 660 or less, optionally 650 or less, optionally 640 or less.

[0101] In some embodiments, the light has a wavelength between 870-890 nm, inclusive.

[0102] In some embodiments, the light has a wavelength between 750-870 nm, inclusive, optionally between 820-840 nm, inclusive.

[0103] In some embodiments, the light has a wavelength between 650-670 nm, inclusive.

[0104] In some embodiments, the light has a wavelength between 595-615 nm, inclusive.#124545638vl 18Attorney Docket No. 500187-00015 PATENT

[0105] In some embodiments, the light has a wavelength between 575-675 nm, inclusive, optionally between 620-640 nm, inclusive.

[0106] In some embodiments, the light a wavelength between 490-580 nm, inclusive, optionally between 515-550 nm. inclusive.

[0107] In some embodiments, the light has a wavelength between 405-425 nm, inclusive.

[0108] In some embodiments, the light is coherent light. In some embodiments, the light is noncoherent light.

[0109] Also provided are embodiments wherein any embodiment above may be combined with any one or more of these embodiments, provided the combination is not mutually exclusive.Definitions

[0110] As used in this specification and the appended claims, the singular forms “a,” “an” and "the" include plural referents unless the context clearly dictates otherwise. As example, “a” photoactive agent may refer to one or more photoactive agents unless otherwise indicated. The terms “a” (or "an"), as well as the terms “one or more." and “at least one’" can be used interchangeably herein.

[0111] It is understood that wherever aspects are described herein with the language “comprising,” otherwise analogous aspects described in terms of “consisting of’ and / or “consisting essentially of’ are also provided. Thus, while the compositions disclosed herein comprise a photoactive agent, or a photoactive agent supplied in a delivery system, the compositions disclosed herein may consist essentially of, or consist of a photoactive agent, or a photoactive agent supplied in a delivery system. As used herein, “consists essentially of’ means that the composition includes a photoactive agent, or a photoactive agent supplied in a delivery system, and may include additional, unlisted elements or components, so long as those additional elements do not materially affect the basic and novel characteristics of the composition, whereas “consists of’ excludes any additional elements not explicitly listed.

[0112] Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges.

[0113] The term “composition,” as used herein, refers broadly to a composition of matter. More particularly, the compositions disclosed herein are intended to provide or amplify a therapeutic or#124545638vl 19Attorney Docket No. 500187-00015 PATENTcosmetic benefit to a subject. Unless otherwise indicated, a composition is intended for application to the skin of the subject. A composition may comprise one or more components that provide benefit to the subject in the absence of the light-triggered mechanism triggered herein. Such components may, without limitation, improve hydration, decrease irritation, and provide a pleasing aroma. A composition may contain one or more components that improve the physical properties of the material. Such components may, without limitation, affect the rheology of the composition. A composition may contain one or more components that preserve the overall composition in general, or a photoactive agent in particular. Certain photoactive agents may be susceptible to deterioration over time. This deterioration may be due to, without limitation, oxidation, free-radical reactivity, or bleaching, and the efficacy of the composition may decrease over time due to such mechanisms. Components to reduce or block deterioration of photoactive agents may therefore be incorporated into a composition, in order to prolong efficacy.

[0114] In some embodiments, a composition is provided in a state suitable for self-administration by a consumer. In some embodiments, a composition is provided in a ready -to-use state that can be self-administered by the consumer subsequent to purchase, without a requirement for assistance or intervention by a device or third party. In some embodiments, the consumer is also provided with a device which is operated subsequent to self-administration of the composition by the consumer. The device may, without limitation, provide a suitable light source for illuminating the photoactive agent within the composition, thereby initiating the benefit to the consumer. In some embodiments, the composition and the device are provided in a standalone package. In some embodiments, the composition and the device are provided separately, with the device being configured to receive a supply of composition. Optionally, the supply of composition can be replenished after initial use of the device.

[0115] An “effective amount” of a therapeutic or cosmetic agent, such as the disclosed photoactive agent(s), is an amount sufficient to carry out a specifically stated purpose. An “effective amount” can be determined empirically and in a routine manner, in relation to the stated purpose. Thus, used herein, the term “effective amount” refers to a dosage sufficient to provide treatment for the condition being treated, or to achieve a certain cosmetic effect (e.g, reduction in wrinkles or increase in skin flexibility). This can vary depending on the subject, the condition and the treatment being affected, or the expected therapeutic and / or cosmetic effect. The exact amount that is required will vary from subject to subject, depending on any of the subject's age, ethnicity, gender, and general condition of the subject, the particular carrier or adjuvant being used, mode of administration, and the like. As such, the effective amount will vary based on the particular#124545638vl 20Attorney Docket No. 500187-00015 PATENTcircumstances, and an appropriate effective amount can be determined in a particular case by one of ordinary skill in the art using only routine experimentation.

[0116] The term “therapeutically effective amount'’ refers to an amount of the disclosed photoactive agent, alone or in combination with another agent, which is effective to “treat” a disease or disorder in a subject. The term “cosmetically effective amount” refers to an amount of the disclosed photoactive agent, alone or in combination with another agent, which is effective to “improve” a skin condition in a subject or mammal.

[0117] The term “topical administration” as applied to the compositions and methods of the instant disclosure refers to the application of a therapeutic agent or cosmetic agent, such as in microcapsule form, to the skin or to mucosal tissue, for example, for the treatment of various skin conditions or disorders.

[0118] The term “transdermal” as used herein refers to the delivery of a therapeutic or cosmetic agent, e.g., photoactive agent of the disclosure, through the skin barrier, such that at least some portion of the photoactive agent reaches underlying layers of the skin.

[0119] Unless otherwise indicated, the term “visible light,” as used herein, refers to light having a wavelength between about 380 nm and 700 nm. Unless otherwise indicated, the term “near-infrared.” as used herein, refers to light having a wavelength between about 700 nm and 2500 nm. Unless otherwise indicated, the term “near ultraviolet,” as used herein, refers to light having a wavelength between about 300 nm and 400 nm. Unless otherwise indicated, the term “near-visible,” as used herein, refers to light in either the near-infrared or the near-ultraviolet light regions of the spectrum.

[0120] Unless otherwise indicated, the term “UVA” or “ultraviolet-A,” refers to light having a wavelength between 315 nm and 400 nm. Unless otherwise indicated, the term “UVB” or “ultraviolet-B,” refers to light having a wavelength between 280 nm and 315 nm.

[0121] The term “skin,” as used herein, refers broadly to the organ in the human body that constitutes substantially the entirety of the outer surface of a person. The term also encompasses discrete organs within the skin, including but not limited to glands (both oil and sweat glands), lymphatic vessels, hair follicles, adipose tissue, blood vessels, and nerves. Skin is generally subdivided into three regions: epidermis, dermis, and superficial fascia (also known as hypodermis). The term includes certain distinctive proteins found throughout skin, including but not limited to elastin and collagen, and certain distinctive polysaccharides, including but not limited to glycosaminoglycans.#124545638vl 21Attorney Docket No. 500187-00015 PATENT

[0122] The term “skin” is understood to exclude hair and nails; however, the term encompasses hair follicles within the skin, and the skin underneath nails. The term “skin” is understood to include specialized tissue that covers particular regions of the body, including lips and urogenital areas. The term “skin” is further understood to include specialized cells, including but not limited to melanocytes, adipocytes, fibroblasts, keratinocytes, Langerhans cells, Merkel cells, and macrophages.

[0123] The term “hair” as used herein refers to keratin-based filamentous structures comprising a cuticle, cortex, and optionally a medulla, extending from a mammalian follicle. The term includes untreated and treated fibers, including those that have been colored, bleached, permed, relaxed, or otherwise modified. The term encompasses individual fibers as well as collections of fibers. The term may specifically refer to terminal hair, defined as thick, long, and pigmented keratinous fibers produced by mature follicles, in contrast to vellus hair. Terminal hair includes scalp hair and other adult hair types such as facial, axillary, and pubic hair.

[0124] The term “microcapsule,” as used herein, refers to a particle consisting of a shell comprising a wall-forming material and an encapsulated core located within the shell. The size of the microcapsule is without limit. In some embodiments, the microcapsule has an average size, as determined by dynamic light scattering or scanning electron microscopy (SEM) ranging from between 10 nm and 10 pm, inclusive, optionally between 100 nm and 1 pm, inclusive, optionally between 150 to 450 nm. inclusive, optionally between 180 to 400 nm, inclusive. In some embodiments, the average size of the microcapsule, as determined by dynamic light scattering or SEM, is between 10 nm and 10 pm, inclusive, optionally between 20 nm and 1.5 pm, inclusive, optionally between 100 to 500 nm, inclusive, optionally between 150 to 600 nm, inclusive, optionally between 180 to 400 nm, inclusive, optionally between 150 to 300 nm, inclusive. This size of the microcapsule will be by the cells, and to release the actives into the cytosol. In a particular embodiment the average size of the microcapsules is 220 nm.

[0125] The following number clauses summarize some non-limiting aspects or embodiments of the disclosure.

[0126] Aspect 1: A composition comprising a photoactive agent, wherein the composition is formulated for topical administration to skin of a subject to provide delivery of the photoactive agent to a target tissue or target cell or target organelle, wherein the photoactive agent, upon irradiation with visible or near-visible light, undergoes a photochemical transformation that#124545638vl 22Attorney Docket No. 500187-00015 PATENTprovides a therapeutic or cosmetic benefit to the subject or amplifies an existing therapeutic or cosmetic benefit to the subject.

[0127] Aspect 2: The composition according to aspect 1, wherein the photoactive agent comprises an algae extract, a vitamin or derivative thereof, a mineral or derivative thereof, or any combination thereof.

[0128] Aspect 3: The composition according to aspect 1 or 2, comprising a cosmetically acceptable carrier, a surfactant, an emollient, a photosensitizer, or any combination thereof.

[0129] Aspect 4: The composition according to aspect 2 or 3, wherein the vitamin or derivative thereof is vitamin A, derivative of vitamin A, vitamin B, derivative of vitamin B, vitamin C, derivative of vitamin C, vitamin E, derivative of vitamin E, or any combination thereof.

[0130] Aspect 5: The composition according to any one of aspects 2 to 4, wherein the algae extract comprises an extract from tetraselmis, chlorella, spirulina, or any combination thereof.

[0131] Aspect 6: The composition according to any one of aspects 2 to 5, wherein the mineral comprises magnesium salt of pyrrolidone carboxylic acid, magnesium ascorbyl phosphate, and / or magnesium sulfate.

[0132] Aspect 7: The composition according to any preceding aspect, wherein the photoactive agent comprises vitamin A or a derivative thereof, such as retinol, retinyl palmitate, retinyl acetate, retinyl retinoate retinyl propionate, retinyl linoleate, retinaldehyde, or any combination thereof.

[0133] Aspect 8: The composition according to any preceding aspect, wherein the photoactive agent comprises vitamin B or a derivative thereof, such as niacin, niacinamide, or a combination thereof.

[0134] Aspect 9: The composition according to any preceding aspect, wherein the photoactive agent comprises vitamin C or a derivative thereof, such as ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, ascorbyl tetraisopalmitate, ascorbyl methylsilanol pectinate, tetrahexyldecyl ascorbate, aminopropyl ascorbyl phosphate, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, or any combination thereof.

[0135] Aspect 10: The composition according to any preceding aspect, wherein the photoactive agent comprises vitamin E or a derivative thereof, such as tocopherol, tocopheryl linoleate, tocopheryl acetate, or any combination thereof.#124545638vl 23Attorney Docket No. 500187-00015 PATENT

[0136] Aspect 11: The composition according to any preceding aspect, wherein the photoactive agent comprises magnesium ascorbyl phosphate, magnesium salt of pyrrolidone carboxylic acid, sodium ascorbyl phosphate, an extract of Spirulina platensis, or any combination thereof.

[0137] Aspect 12: The composition according to any preceding aspect, wherein the photoactive agent comprises a combination of an extract of Spirulina platensis with one or more of magnesium ascorbyl phosphate, magnesium salt of pyrrolidone carboxylic acid, or sodium ascorbyl phosphate.

[0138] Aspect 13: The composition according to any preceding aspect, wherein the photoactive agent comprises a combination of an extract of Spirulina platensis, magnesium ascorbyl phosphate, and magnesium salt of pyrrolidone carboxylic acid.

[0139] Aspect 14: The composition according to any preceding aspect, wherein the photoactive agent comprises a combination of spirulina, Mg PCA, and MAP provided in a ratio of spirulina to (Mg PCA + MAP) of 200:0 to 0:200, such as 200: 1 to 1:200, or 100: 1 to 1: 100, or 50: 1 to 1:50, or 40:1 to 1:40, or 20:1 to 1:20, or 10: 1 to 1:10, or 5:1 to 1:5, or 2:1 to 1:2, or 1:1 (spirulina: (Mg PCA + MAP)), wherein the Mg PCA and MAP may be provided in the combination of (Mg PCA + MAP) in a ratio of 200:0 to 0:200, such as 200:1 to 1:200, or 100:1 to 1:100, or 50:1 to 1:50, or 10:1 to 1:10, or 5:1 to 1:5, or 2:1 to 1:2, or 1:1.

[0140] Aspect 15: The composition according to any preceding aspect, comprising the photoactive agent either individually, or in combination when more than one is included, at 0.001 to 99.9 % by weight, or 0.01 to 50 % by weight, or 0.01 to 25.0 % by weight, or 0.01 to 10.0 % by weight, or 0.01 to 5.0 % by weight, or 0.01 to 2.5 % by weight, or 0.01 to 1.0 % by weight, or 0.01 to 0.5 % by weight, based on the total weight of the composition.

[0141] Aspect 16: The composition according to any preceding aspect, wherein the photoactive agent is provided in a delivery’ system.

[0142] Aspect 17: The composition according to aspect 16, wherein the delivery system comprises a liposome, a microvesicle, or a microcapsule.

[0143] Aspect 18: The composition according to aspect 16 or 17, wherein the delivery’ system has an average size, as determined by dynamic light scattering or scanning electron microscopy (SEM), from 10 nm to 10 pm, or from 20 nm to 1.5 pm, or from 100 to 500 nm, or from 150 to 600 nm, or from 180 to 400 nm, or from 150 to 300 nm.#124545638vl 24Attorney Docket No. 500187-00015 PATENT

[0144] Aspect 19: The composition according to any one of aspect 16 to 18, wherein the delivery system is configured to deliver the photoactive agent to a target tissue, cell, or organelle in the subject.

[0145] Aspect 20: The composition according to any one of aspect 16 to 19. wherein the delivery system comprises a surface modification, such as antibodies, antibody fragments, peptides, ligands, carbohydrates, aptamers, or other receptor-binding molecules capable of selectively associating with markers expressed on target cells.

[0146] Aspect 21: The composition according to any one of aspect 16 to 20, wherein the photoactive agent is included in the delivery system at from 0.01 to 99.9 % by weight, or 0.01 to 50 % by weight, or 0.1 to 50 % by weight, or 0.01 to 10 % by weight, or 0.1 to 5 % by weight, or 1 to 5 % by weight, based on the total weight of the delivery system comprising the photoactive agent; and / or wherein the delivery system comprising the photoactive agent may be included in the disclosed composition at from 0.01 to 99.9 % by weight, or 0.01 to 50 % by weight, or 0.1 to 25 % by weight, or 0.1 to 10 % by weight.

[0147] Aspect 22: A method for providing or amplifying a therapeutic or cosmetic benefit to a subject, the method comprising applying a composition according to any one of aspects 1 to 21, and irradiating the skin with visible or near-visible light.

[0148] Aspect 23: The method according to aspect 22, wherein the light is visible light, or is near-infrared light, or is red light.

[0149] Aspect 24: The method according to aspect 22, wherein the light has a wavelength of 750-870 nm, 870-890 nm, 820-840 nm, 650-670 nm, 595-615 nm, 575-675, 620-640 nm, 490-580 nm, 515-550 nm, or 405-425 nm.

[0150] Aspect 25: The method according to aspect 22, wherein the light has a wavelength of from 575 nm to 740 nm, or from 620 nm to 640 nm.

[0151] Aspect 26: The method according to any one of aspects 22 to 25, wherein the therapeutic or cosmetic benefit comprises wound healing, stimulation of production of skin proteins such as collagen and elastin, protection of such proteins, alteration of mitochondrial function, alteration of ATP production, decrease in the amount of oxidizing species, or any combination thereof.

[0152] Aspect 27: The method according to any one of aspects 22 to 26, wherein the method increases collagen levels in the dermis.#124545638vl 25Attorney Docket No. 500187-00015 PATENT

[0153] Aspect 28: The method according to any one of aspects 22 to 27, wherein the method alters ATP production, such as increases ATP production.EXAMPLESExample 1. Materials and MethodsTable 1.Target concentration (jug / mL) Candidate Photoactive AgentsTables 2A & B Table 3 Table 4 Vitamin C derivative - Magnesium Ascorbyl Phosphate (MAP) 100 & 50 N / A N / A Vitamin C derivative - Sodium Ascorbyl Phosphate (SAP) N / A N / A 10 Magnesium salt of pyrrolidone carboxylic acid (PCA) N / A 30 N / A Spirulina platensis extract 100 250 N / A

[0154] Stock solutions of each candidate photoactive agent were prepared by dissolving or predispersing the candidate in either (i) an aqueous (water) vehicle for MAP, SAP, or (ii) an ethanol-water-glycerin (70:20: 10) vehicle for the Spirulina platensis extract, Magnesium PC A, followed by sonication for 30 minutes if needed. The stock solution would later be added to the cell culture medium (containing neonatal human dermal fibroblasts) in an amount that yielded the desired concentrations listed above.

[0155] Table 1 provides the identities of the various candidate photoactive agents and the target concentrations of those agents when included in the fibroblast assays of Examples 2-4.

[0156] Also prepared were the following controls: aqueous (water) vehicle, and ethanol-water- glycerin (70:20:10) vehicle.Example 2. Assay protocol: ATP production

[0157] Normal human neonatal dermal fibroblasts were seeded in a 96-well plate at a density of 20,000 cells / well and cultured for two days. On Day 2, either (A) hydrogen peroxide was added, and then 4 hours later, either the control (the aqueous or ethanol-water-glycerin vehicles) or the candidate photoactive agent was added to individual wells, or (B) no hydrogen peroxide was added and either the control or the candidate photoactive agent was added to individual wells.#124545638vl 26Attorney Docket No. 500187-00015 PATENT

[0158] The plate was then irradiated for 3 minutes with an LED panel having an optical output of 40 mW / cm2(wavelength 630 nm). The same treatment was performed with the same candidate photoactive agents but without red light exposure from the LED panel.

[0159] After the overnight incubation, intracellular ATP was measured. An ATP quantification luminescence assay was used to assess the ATP output in cell populations exposed to the different experimental conditions, i.e., negative controls (the aqueous or ethanol-water-glycerin vehicles), different candidate photoactive agents, concentrations of the candidate photoactive agents, and exposure to red light. The percentage improvement in ATP value for each treatment over the negative control (the aqueous or ethanol-water-glycerin vehicle) was calculated. To evaluate the activating effect of red light, the percentage improvement observed with each candidate active agent when exposed to red light (versus the percentage improvement without red light exposure) was compared. A ranking was assigned to each candidate photoactive agent based on the degree to which red light has enhanced the treatment effect over the absence of red light: "++++“ 75 % or more; “+++” 50 % to 74 %; “++” 25 % to 49 %; “+” 5 % to 24 %; 5 % or less.Example 3. Assay protocol: collagen production

[0160] Normal human neonatal dermal fibroblasts were seeded and cultured in a 96-well plate at a density of 50,000 cells / well (Day 0). The next day (Day 1), the candidate photoactive agents and the negative controls (water or ethanol-water-glycerin vehicle) were added.

[0161] After 5 hours, the plate was irradiated for 3 minutes with the LED panel described above. The same treatment was also performed with the same candidate photoactive agents but without red light exposure from the LED panel. The cell culture was then pursued for 72 hours, followed by the collection of cell media to perform sandwich enzyme-linked immunosorbent assay (ELISA) for Type I collagen.

[0162] The percentage improvement in collagen-I quantity for each treatment over the negative control (the aqueous or ethanol-water-glycerin vehicle) was first computed. Next, to evaluate the activating effect of red light on the treatment, the percentage improvement observed with each treatment when exposed to red light (versus the percentage improvement without red light exposure) was compared. A ranking was assigned to each treatment based on the degree to which red light has enhanced the treatment effect over the absence of red light: ‘‘++-1-1-” 75 % or more; “+++” 50 % to 74 %; “++” 25 % to 49 %; “+” 5 % to 24 %; 5 % or less.#124545638vl 27Attorney Docket No. 500187-00015 PATENTExample 4. Assay protocol: cell metabolic activity

[0163] Normal human neonatal dermal fibroblasts were seeded in a 96-well plate at a density of -7,500 cells / well. The cells were cultured for 2 days. On Day 2, the candidate active agents were added. The plate was then irradiated for 3 minutes with the LED panel described above. The same treatment was performed with the same candidate active agents but without red light exposure from the LED panel.

[0164] On Day 5, cellular metabolism was measured using the MTT assay. The level of metabolic activity produced by the treatment with and without red light were compared against each other and versus the negative control.Example 5. Results of Red Light Treatment

[0165] Results of the ATP production assays described in Examples 2 and 3 are presented in Tables 2A and 3, results of the collagen production assays described in Example 2 are presented in Table 2B, and results of the metabolic activity assay described in Example 4 are presented in Table 4. Table 2A lists results of the ATP production protocol (A), wherein hydrogen peroxide was added 4 hours before the test materials were added, and Table 3 lists results of the ATP production protocol (B), wherein test materials were added without prior exposure of the cells to hydrogen peroxide.

[0166] The results of these assays indicate that a natural ingredient such as Spirulina platensis extract, or a vitamin ingredient such as magnesium ascorbyl phosphate or sodium ascorbyl phosphate, and / or a mineral ingredient such as magnesium PCA can be activated by red light exposure to produce a higher level of ATP or cellular energy or metabolic activity, and / or a higher level of collagen production, all indicative of potential positive biological effects of the treatment.

[0167] With specific reference to the results shown in Table 3, the results also demonstrate a strong synergistic effect of the combination of a natural ingredient such as Spirulina platensis extract and a mineral ingredient such as magnesium PCA. Without red light exposure, none of magnesium PCA alone, Spirulina platensis extract alone, or the combination thereof at the use levels tested yielded a meaningful increase in ATP over the negative control. Similarly, at the use levels tested with red light exposure, neither magnesium PCA alone nor Spirulina platensis extract alone yielded a noticeable increase in ATP production over the negative control. However, the combination of magnesium PCA and Spirulina platensis extract under red light exposure resulted in an ATP production level that was: (i) 54 % greater than the control (p < 0.01), i.e., as compared#124545638vl 28Attorney Docket No. 500187-00015 PATENTto vehicle control alone; (ii) 51 % greater than samples not exposed to red light (p < 0.05); and (iii) 50 % or more (p < 0.05) greater than each active agent tested separately with exposure to red light.

[0168] These experimental findings clearly demonstrate the strong synergistic effect in the enhancement of ATP levels when combining the natural ingredient Spirulina platensis extract with the mineral ingredient magnesium PCA upon red light exposure (an effect which was not observed when red light is not present or when the ingredients were not used together).Table 2AImprovement in ATP Photoactive AgentProduction with Red Light MAP (100 pg / mL) ++++Spirulina platensis extract (100 [lg / mL) ++++Ranking assigned to each treatment based on the degree to which red light has enhanced the treatment effect over the absence of red light: “++++’’ 75 % or more; “+++” 50 % to 74 %; “++” 25 % to 49 %; “+’ 5 % to 24 %; 5 % or less. NT - not tested.Table 2BImprovement in Collagen Photoactive AgentProduction with Red Light MAP (50 pg / mL) ++++Ranking assigned to each treatment based on the degree to which red light has enhanced the treatment effect over the absence of red light: “++++” 75 % or more; “+++” 50 % to 74 %; “++” 25 % to 49 %; “+” 5 % to 24 %; 5 % or less. NT - not tested.Table 3Improvement in ATP production Candidate over the negative control without red light with red light IndividualSpirulina platensis - 250 pg / mL - - Magnesium PCA - 30 pg / mL - - CombinationSpirulina platensis - 250 pg / mL +- +++Magnesium PCA - 30 pg / mLRanking assigned to each treatment based on the degree to which the treatment has enhanced the observed biological effect over the negative control: “++++” 75 % or more; 'M-++7’ 50 % to 74 %; “++” 25 % to 49 %; “+” 5 % to 24 %; 5 % or less.#124545638vl 29Attorney Docket No. 500187-00015 PATENTTable 4Improvement in Metabolic Activity Candidate with Red Light ExposureSodium Ascorbyl Phosphate ++Ranking assigned to each treatment based on the degree to which the treatment has enhanced the observed biological effect over the negative control: “++++” 75 % or more; “+++” 50 % to 74 %; “++” 25 % to 49 %; “+” 5 % to 24 %; 5 % or less.Example 6: Preparation and Testing o f Topical Compositions Containing a Combination of Ingredients

[0169] Objective: To evaluate whether compositions containing the combination of various ingredients can exhibit improved biological effects (such as cellular metabolism, mitochondrial function, anti-inflammatory effects, collagen production, etc.) when exposed to red light versus without red light exposure.

[0170] Materials and Methods: Light Source: An LED panel with an optical output of 40 mW / cm2(wavelength of 630 nm); Model: 3-D full-thickness human skin equivalent model. The specific test materials include vehicle (Control) and various formula compositions comprising the vehicle with 0.001%-10% Spirulina, 0.001%-10% Magnesium Ascorbyl Phosphate, and 0.001%-10% Magnesium PCA.

[0171] Procedure: The tissues for the 3-D Skin Model are first acclimatized. Once ready (Day 1), the various test compositions are applied to different tissue samples and irradiated for 3 minutes with the LED panel described above. The same treatment is performed with the same test materials but without red light exposure from the LED panel. The same treatment and irradiation steps are repeated once a day for 3 days (Days 2-4). On Day 5, mitochondrial function and cellular metabolism are measured using the MTT assay and / or an ATP assay, and the inflammatory profile and collagen production are measured by ELISA. The level of biological effects produced by the treatment with and without red light are compared against each other and versus the untreated and vehicle controls.

[0172] Results: One or more of the treatments are predicted to demonstrate a more significant improvement in biological effects when exposed to red light versus without red light (p < 0.05). The experimental findings from this example may indicate that a composition containing certain photoactive agents can be activated and boosted by red light exposure to yield higher levels of#124545638vl 30Attorney Docket No. 500187-00015 PATENTimprovements in biological effects such as cellular metabolism, mitochondrial function, antiinflammatory effects, collagen production, etc.

[0173] While specific embodiments of the invention have been described in detail, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements disclosed are meant to be illustrative only and not limiting as to the scope of disclosed concept which is to be given the full breadth of the claims appended and any and all equivalents thereof.#124545638vl 31

Claims

Attorney Docket No. 500187-00015 PATENTCLAIMS1. A composition comprising a photoactive agent, wherein:the photoactive agent undergoes a photochemical transformation that provides a therapeutic or cosmetic benefit to a subject or amplifies an existing therapeutic or cosmetic benefit to the subject when applied to the skin of the subject and irradiated with visible or near- visible light.

2. The composition of claim 1, wherein:the skin of the subject can be exposed to the composition with minimal adverse effects, and the composition provides delivery of the photoactive agent to a target tissue or target cell or target organelle.

3. The composition of claim 2, wherein the target tissue or target cell or target organelle is located in the skin.

4. The composition of claim 3, wherein irradiation of the photoactive agent after delivery to the target tissue or target cell or target organelle in the skin of a subject provides a therapeutic or cosmetic benefit to the subject or amplifies an existing therapeutic or cosmetic benefit to the subject.

5. The composition of claim 3, wherein irradiation of the photoactive agent after delivery to the target tissue or target cell or target organelle in the skin of a subject produces an agent that is capable of providing or amplifying a therapeutic or cosmetic benefit to the subject.

6. The composition of claim 3, wherein the target tissue, target cell, or target organelle is located in a region of the skin chosen from the dermis and superficial fascia.

7. The composition of claim 3, wherein the target tissue, target cell, or target organelle is located in the epidermis.

8. The composition of claim 3, wherein the target tissue, target cell, or target organelle is located in the dermal-epidermal junction.

9. The composition of claim 6, wherein the target cell is a fibroblast.

10. The composition of claim 7, wherein the target cell is a keratinocyte.

11. The composition of claim 6, wherein the target organelle is a mitochondrion.

12. The composition of claim 7 wherein the target organelle is a mitochondrion.#124545638vl 32Attorney Docket No. 500187-00015 PATENT13. The composition of claim 1, wherein the light is within the combined visible and near-infrared region of the spectrum.

14. The composition of claim 13, wherein the light is near-infrared light.

15. The composition of claim 13, wherein the light is red light.

16. The composition of claim 13, wherein the light has a wavelength between 870-890 nm, inclusive.

17. The composition of claim 13, wherein the light has a wavelength between 750-870 nm, inclusive, optionally between 820-840 nm, inclusive.

18. The composition of claim 13. wherein the light has a wavelength between 650-670 nm, inclusive.

19. The composition of claim 13, wherein the light has a wavelength between 595-615 nm, inclusive.

20. The composition of claim 13, wherein the light has a wavelength between 575-675 nm, inclusive, optionally between 620-640 nm, inclusive.

21. The composition of claim 13, wherein the light has a wavelength between 490-580 nm, inclusive, optionally between 515-550 nm, inclusive.

22. The composition of claim 13, wherein the light has a wavelength between 405-425 nm, inclusive.

23. The composition of claim 1, wherein the photoactive agent comprises a chromophore.

24. The composition of claim 23, wherein the chromophore is polycyclic.

25. The composition of claim 24, wherein the chromophore is a porphyrin.

26. The composition of claim 23, wherein the photoactive agent comprises a naturally occurring chromophore.

27. The composition of claim 26, wherein the photoactive agent comprises a chromophore from a plant, marine, aquatic, or animal source.

28. The composition of claim 1, wherein the photoactive agent is a natural product or an extract thereof.#124545638vl 33Attorney Docket No. 500187-00015 PATENT29. The composition of claim 28, wherein the photoactive agent is a natural product chosen from algae, plankton, seaweed, Lindera, Camellia, Silybum, Aspalathus. Glycyrrhiza, Curcuma, Frangula, Vitis, or any combination thereof.

30. The composition of claim 29, wherein the algae, plankton, or seaweed extract comprises an extract from Tetraselmis, Chlorella, Spirulina, Ulva, Dunaliella, Fucus, Laminaria, Chondrus, or any combination thereof.

31. The composition of claim 1, wherein the photoactive agent is an antioxidant or skin conditioning agent.

32. The composition of claim 31, wherein the antioxidant or skin conditioning agent is vitamin A or a derivative thereof.

33. The composition of claim 32, wherein the antioxidant or skin conditioning agent is chosen from retinol, retinyl palmitate, retinyl acetate, retinyl retinoate retinyl propionate, retinyl linoleate and retinaldehyde.

34. The composition of claim 31, wherein the antioxidant or skin conditioning agent is vitamin B or a derivative thereof.

35. The composition of claim 34, wherein the antioxidant or skin conditioning agent is chosen from niacin and niacinamide.

36. The composition of claim 31, wherein the antioxidant or skin conditioning agent is vitamin C or a derivative thereof.

37. The composition of claim 36, wherein the antioxidant or skin conditioning agent is chosen from ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, ascorbyl tetraisopalmitate, ascorbyl methylsilanol pectinate, tetrahexyldecyl ascorbate, aminopropyl ascorbyl phosphate, sodium ascorbyl phosphate and magnesium ascorbyl phosphate.

38. The composition of claim 31, wherein the antioxidant or skin conditioning agent is vitamin E or a derivative thereof.

39. The composition of claim 38, wherein the antioxidant or skin conditioning agent is chosen from tocopherol, tocopheryl linoleate and tocopheryl acetate.

40. The composition of claim 31, wherein the antioxidant or skin conditioning agent is chosen from resveratrol, ubiquinone, ubiquinol, hydroxy decyl ubiquinone, ferulic acid, glutathione, polyphenols, beta carotene, zinc, and quercetin.#124545638vl 34Attorney Docket No. 500187-00015 PATENT41. The composition of claim 1, wherein the photoactive agent comprises a mineral agent.

42. The composition of claim 41, wherein the mineral agent is chosen from magnesium salt of pyrrolidone carboxylic acid (Mg PCA). magnesium sulfate, magnesium chloride, magnesium hydroxide, magnesium stearate, magnesium gluconate, magnesium lactate, magnesium porphyrins, magnesium ascorbyl phosphate (MAP), hematite, copper oxide, cuprous oxide, copper peptide, gold or silver nanoparticles, or any combination thereof.

43. The composition of claim 1, wherein the photoactive agent comprises an algae extract, a vitamin or derivative thereof, a mineral agent, or any combination thereof.

44. The composition of claim 43, comprising the photoactive agent at 0.001 to 99.9% by weight, 0.001 to 50% by weight, 0.001 to 25.0 % by weight, or 0.01 to 10.0 % by weight, or 0.01 to 5.0 % by weight, or 0.01 to 1.0 % by weight, based on the total weight of the composition.

45. The composition of claim 43, wherein the vitamin or derivative thereof is vitamin A, derivative of vitamin A, vitamin B, derivative of vitamin B, vitamin C, derivative of vitamin C, vitamin E, derivative of vitamin E, or any combination thereof.

46. The composition of claim 43, wherein the algae extract comprises an extract from Tetraselmis, Chlorella, Spirulina, Ulva, Dunaliella, Fucus, Laminaria, Chondrus, or any combination thereof.

47. The composition of claim 43, wherein the mineral agent comprises magnesium ascorbyl phosphate (MAP), magnesium salt of pyrrolidone carboxylic acid (Mg PCA), magnesium sulfate, magnesium chloride, magnesium hydroxide, magnesium stearate, magnesium gluconate, magnesium lactate, magnesium porphyrins, or a combination thereof.

48. The composition of claim 1, wherein the photoactive agent comprises magnesium ascorbyl phosphate (MAP), magnesium salt of pyrrolidone carboxylic acid (Mg PCA), sodium ascorbyl phosphate, an extract of Spirulina platensis, or any combination thereof.

49. The composition of claim 48, comprising the photoactive agent at 0.001 to 99.9% by weight. 0.001 to 50% by weight. 0.001 to 25.0 % by weight, or 0.01 to 10.0 % by weight, or 0.01 to 5.0 % by weight, or 0.01 to 1.0 % by weight, based on the total weight of the composition.

50. The composition of claim 1, wherein the photoactive agent comprises a combination of an extract of Spirulina platensis with one or more of magnesium ascorbyl phosphate, magnesium salt of pyrrolidone carboxylic acid, or sodium ascorbyl phosphate.#124545638vl 35Attorney Docket No. 500187-00015 PATENT51. The composition of claim 50, comprising the photoactive agent at 0.001 to 99.9% by weight. 0.001 to 50% by weight. 0.001 to 25.0 % by weight, or 0.01 to 10.0 % by weight, or 0.01 to 5.0 % by weight, or 0.01 to 1.0 % by weight, based on the total weight of the composition.

52. The composition of claim 1, wherein the photoactive agent comprises a combination of an extract of Spirulina platensis, magnesium salt of pyrrolidone carboxylic acid, and magnesium ascorbyl phosphate.

53. The composition of claim 52, comprising the photoactive agent at 0.001 to 99.9% by weight, 0.001 to 50% by weight, 0.001 to 25.0 % by weight, or 0.01 to 10.0 % by weight, or 0.01 to 5.0 % by weight, or 0.01 to 1.0 % by weight, based on the total weight of the composition.

54. The composition of claim 1, wherein the photoactive agent comprises Spirulina platensis, magnesium salt of pyrrolidone carboxylic acid, and magnesium ascorbyl phosphate, wherein the Spirulina platensis, magnesium salt of pyrrolidone carboxylic acid, and magnesium ascorbyl phosphate are provided in a ratio of spirulina to Mg PCA + MAP of 200: 1 to 1:200 (spirulina: (Mg PCA + MAP)), wherein the ratio of Mg PCA to MAP provided in the combination of spirulina, Mg PCA, and MAP comprises 200:1 to 1:200 (Mg PCA: MAP).

55. The composition of claim 54, wherein the Spirulina platensis, magnesium salt of pyrrolidone carboxylic acid, and magnesium ascorbyl phosphate are provided in a ratio of spirulina to Mg PCA + MAP of 100:1 to 1:100 or 40:1 to 1:40 or 20:1 to 1:20 (spirulina: (Mg PCA + MAP)), wherein the ratio of Mg PCA to MAP provided in the combination of spirulina, Mg PCA, and MAP comprises 200:1 to 1:200 (Mg PCA: MAP).

56. The composition of claim 54, comprising the photoactive agent at 0.001 to 99.9% by weight, 0.001 to 50% by weight, 0.001 to 25.0 % by weight, or 0.01 to 10.0 % by weight, or 0.01 to 5.0 % by weight, or 0.01 to 1.0 % by weight, based on the total weight of the composition.

57. The composition of claim 1, comprising the photoactive agent at 0.001 to 99.9% by weight, 0.001 to 50% by weight, 0.001 to 25.0 % by weight, or 0.01 to 10.0 % by weight, or 0.01 to 5.0 % by weight, or 0.01 to 1.0 % by weight, based on the total weight of the composition.

58. The composition of claim 1, wherein the composition is provided in a delivery system.#124545638vl 36Attorney Docket No. 500187-00015 PATENT59. The composition of claim 58, wherein the delivery system is chosen from a liposome, a microvesicle, and a microcapsule.

60. The composition of claim 58, wherein the delivery system comprises surface modification that targets the target tissue or target cell or target organelle.

61. The composition of claim 60. wherein the surface modification comprises antibodies or fragments thereof, peptides, ligands, carbohydrates, aptamers, or other receptor-binding molecules capable of selectively associating with markers expressed on the target tissues or target cell, or target organelle.

62. The composition of claim 58, wherein the delivery system comprises a polymeric shell.

63. The composition of claim 58, wherein the delivery system comprises exosomes.

64. The composition of claim 58, wherein the delivery system comprises a nanoemulsion.

65. The composition of claim 58, wherein the delivery system has an average size, as determined by dynamic light scattering or scanning electron microscopy (SEM), between 10 nm and 10 pm, inclusive, optionally between 20 nm and 1.5 pm, inclusive, optionally between 100 to 500 nm, inclusive, optionally between 150 to 600 nm, inclusive, optionally between 180 to 400 nm, inclusive, optionally between 150 to 300 nm, inclusive.

66. The composition of claim 58, wherein the delivery system directs delivery of the composition to a target tissue or target cell or target organelle in the subject.

67. The composition of claim 66, wherein the photoactive agent undergoes a photochemical transformation at the target tissue or target cell or target organelle in the subject.

68. The composition of claim 66, wherein the composition provides a therapeutic or cosmetic benefit to the target tissue or target cell or target organelle in the subject or amplifies an existing therapeutic or cosmetic benefit at the target tissue or target cell or target organelle in the subject.

69. The composition of claim 58, wherein the photoactive agent is included in the delivery system at from 0.01 to 99.9 % by weight, or 0.1 to 50 % by weight, or 0.1 to 10 % by weight, or 1 to 5 % by weight, based on the total weight of the delivery system comprising the photoactive agent; and / or wherein the delivery system comprising the photoactive agent may be included in the disclosed composition at from 0.01 to 99.9 % by weight, or 0.01 to#124545638vl 37Attorney Docket No. 500187-00015 PATENT50 % by weight, or 0.1 to 25 % by weight, or 0.1 to 10 % by weight, based on the total weight of the composition.

70. The composition of claim 1, wherein the composition accumulates preferentially in a target tissue or target cell or target organelle in the subject.

71. The composition of claim 70, wherein the photoactive agent undergoes a photochemical transformation at the target tissue or target cell or target organelle in the subject.

72. The composition of claim 70, wherein the composition provides a therapeutic or cosmetic benefit to the target tissue or target cell or target organelle in the subject or amplifies an existing therapeutic or cosmetic benefit at the target tissue or organelle in the subject.

73. The composition of claim 1, further comprising a cosmetically acceptable carrier.

74. The composition of claim 1, further comprising a surfactant.

75. The composition of claim 1, further comprising an emollient.

76. The composition of claim 1, further comprising a photosensitizer.

77. A method for providing or amplifying a therapeutic or cosmetic benefit to a subject, the method comprising the steps of:applying the composition according to any one of claims 1 to 76 to the skin of the subject, andirradiating the skin with light from a light source, wherein the light is within the visible or near-visible region of the spectrum.

78. The method of claim 77, wherein the therapeutic or cosmetic benefit to the subject is a therapeutic benefit to the subject.

79. The method of claim 78, wherein the therapeutic benefit is a therapeutic benefit to the skin.

80. The method of claim 79, wherein the therapeutic benefit to the skin consists of decreased sensitivity, irritation, or pruritus.

81. The method of claim 79, wherein the therapeutic benefit to the skin consists of decreased susceptibility to a dermatological disease.

82. The method of claim 81, wherein the dermatological disease is dermatitis.

83. The method of claim 81, wherein the dermatological disease is skin cancer.#124545638vl 38Attorney Docket No. 500187-00015 PATENT84. The method of claim 79, wherein the therapeutic benefit to the skin consists of decreased susceptibility to excessive exposure to intense irradiation in the visible or ultraviolet spectrum.

85. The method of claim 84, wherein the intense irradiation in the visible or ultraviolet spectrum is sunlight.

86. The method of claim 77, wherein the therapeutic or cosmetic benefit to the subject is a cosmetic benefit to the subject.

87. The method of claim 86, wherein the cosmetic benefit is a cosmetic improvement of the skin.

88. The method of claim 87, wherein the cosmetic improvement of the skin consists of an improvement in the plumpness, firmness, elasticity, or tightness of the skin.

89. The method of claim 87, wherein the cosmetic improvement in the skin consists of a reduction in puffiness or inflammation.

90. The method of claim 87, wherein the cosmetic improvement of the skin consists of an improvement in the texture of the skin.

91. The method of claim 90, wherein the improvement in the texture of the skin consists of a reduction in appearance or size of pores.

92. The method of claim 90, wherein the cosmetic improvement of the skin consists of an improvement in the appearance of lines in the skin.

93. The method of claim 92, wherein the improvement in the appearance of lines in the skin is chosen from reduced visual prominence of the lines, reduced length, width, or depth of the lines, and reduced size or volume of the lines.

94. The method of claim 92, wherein the lines in the skin are chosen from fine lines, forehead lines, perioral smile lines, lines in the chest, lines in the neck, lines in the hands, and lines in other body regions.

95. The method of claim 87, wherein the cosmetic improvement of the skin consists of an improvement in the appearance of wrinkles in the skin.

96. The method of claim 95, wherein the improvement in the appearance of wrinkles in the skin is chosen from reduced number, reduced width, reduced depth, and reduced visual prominence.#124545638vl 39Attorney Docket No. 500187-00015 PATENT97. The method of claim 87, wherein the cosmetic improvement of the skin consists of an improvement in the overall visual appearance of the skin.

98. The method of claim 97, wherein the improvement in the overall visual appearance of the skin is increased uniformity of skin tone.

99. The method of claim 97, wherein the improvement in the overall visual appearance of the skin is chosen from improved skin brightness, luminosity, radiance, youthfulness, and glow.

100. The method of claim 97, wherein the improvement in the visual appearance of the skin consists of decreased redness.

101. The method of claim 97, wherein the improvement in the visual appearance of the skin consists of an improvement in the visual appearance of a localized disfigurement to the skin.

102. The method of claim 101, wherein the improvement in the visual appearance of a localized disfigurement to the skin is a reduction in the number, size, or visual prominence of the disfigurement.

103. The method of claim 101, wherein the localized disfigurement to the skin is chosen from dark spots, blemishes, and hyperpigmented regions.

104. The method of claim 101, wherein the localized disfigurement to the skin is chosen from a subocular, periocular, manual, and podiatric disfigurement.

105. The method of claim 101, wherein the localized disfigurement to the skin is caused or exacerbated by excessive exposure to intense irradiation in the visible or ultraviolet spectrum.

106. The method of claim 101, wherein the intense irradiation in the visible or ultraviolet spectrum is sunlight.

107. The method of claim 77, wherein the therapeutic or cosmetic benefit is chosen from wound healing, stimulation of production of skin proteins such as collagen and elastin, protection of such proteins, alteration of mitochondrial function, alteration of ATP production, alteration of metabolic activity, and decrease in the amount of oxidizing species.

108. The method of claim 77, wherein the therapeutic or cosmetic benefit comprises improvement to terminal hair on a scalp of the subject.#124545638vl 40Attorney Docket No. 500187-00015 PATENT109. The method of claim 108, wherein the therapeutic or cosmetic benefit is chosen from reduced hair loss, increased hair growth, reduced dandruff, reduced seborrheic dermatitis, reduced psoriasis, reduced Contact dermatitis, reduced folliculitis, or any combination thereof.

110. The method of claim 77, wherein the method increases collagen or elastin levels.

111. The method of claim 77, wherein the method accelerates wound healing.

112. The method of claim 77, wherein the method alters mitochondrial function.

113. The method of claim 77, wherein the method alters ATP production.

114. The method of claim 77, wherein the method increases ATP levels.

115. The method of claim 77, wherein the method decreases the amount of oxidizing species.

116. The method of claim 77, wherein the method alters metabolic activity.

117. The method of claim 77, wherein the light is within the combined visible and near-infrared region of the spectrum.

118. The method of claim 117. wherein the light is near-infrared light.

119. The method of claim 117, wherein the light is red light.

120. The method of claim 117, wherein the light has a wavelength between 870-890 nm, inclusive.

121. The method of claim 117. wherein the light has a wavelength between 750-870 nm, inclusive, optionally between 820-840 nm, inclusive.

122. The method of claim 117, wherein the light has a wavelength between 650-670 nm, inclusive.

123. The method of claim 117, wherein the light has a wavelength between 595-615 nm, inclusive.

124. The method of claim 117, wherein the light has a wavelength between 575-675 nm, inclusive, optionally between 620-640 nm, inclusive.

125. The method of claim 117, wherein the light has a wavelength between 490-580 nm, inclusive, optionally between 515-550 nm, inclusive.#124545638vl 41Attorney Docket No. 500187-00015 PATENT126. The method of claim 117, wherein the light has a wavelength between 405-425 nm, inclusive.

127. The method of claim 77, wherein the light is coherent light.

128. The method of claim 77, wherein the light is non-coherent light.#124545638vl 42

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