A vaginal drug delivery device to improve the efficacy of drug delivery through the vagina

Abstract

Disclosed herein are compositions and methods of manufacturing, testing, and using a biocompatible and disposable vaginal suppository, comprising chitosan, collagen, carboxymethyl cellulose, and an enzyme, capable of breaking down vaginal mucous and releasing the active ingredients consistently over extended periods of time. Methods disclosed herein may also include the use of these compositions, methods, and devices for treating vaginal diseases, such as vaginitis, genitourinary syndrome, and other conditions, such as vulvar and vaginal cancer, or cervical cancer.

Description

VABIO.005WO PCTA VAGINAL DRUG DELIVERY DEVICE TO IMPROVE THE EFFICACY OF DRUG DELIVERY THROUGH THE VAGINAINCORPORATION BY REFERENCE TO ANY" PRIORITY APPLICATIONS

[0001] Any and all applications for which a foreign or domestic priority claim is identified, for example, in the Application Data Sheet as filed with the present application, are hereby incorporated by reference under 37 CFR 1.57, and Rules 4.18 and 20.6, including U. S. Provisional Application No. 63 / 720919 filed November 15, 2024, which is hereby incorporated by reference in its entirety.BACKGROUNDField

[0002] The present disclosure relates to the field of medicine and pharmaceutical delivery. More particularly, the present disclosure relates generally to compositions, devices, and methods for the intravaginal delivery of therapeutically effective compounds and compositions.Description

[0003] The ability to deliver drugs intravaginal ly and with local application offers advantages over existing methods of drug delivery, such as orally or intravenously. For example, the direct application of drugs can increase the relative efficacy of the drug within the target tissue while decreasing systemic side effects associated with other delivery methods.

[0004] Despite the putative benefits of intravaginal delivery, there remain challenges that prevent the efficient and effective delivery of drugs within the vagina. Current methods of intravaginal drug delivery include vaginal tablets, vaginal creams, vaginal gels, vaginal rings, and vaginal films. Each of these methods includes notable drawbacks. For example, vaginal tablets, creams, and gels result in a fast drug release within hours, leading to short-term efficacy. Vaginal rings need to be changed or replaced periodically, which can be inconvenient for the consumer. Vaginal films, meanwhile, have a low drug-loading capacity.Additionally, the thick mucus that coats the vaginal wall can interfere with the effective delivery of therapeutics to the target tissue in all of these methods.SUMMARY

[0005] Aspects of the disclosure relate to compositions for intravaginal drug delivery. To effectively deliver active ingredients intravaginally without increasing inflammation or irritation at the delivery site, some embodiments relate to delivery through devices composed of biocompatible and non-toxic materials. Additionally, degradable, non-fnable, and portable devices enhance the usability and accessibility' of such devices while reducing the likelihood of contamination and infection. In some embodiments, the compositions described herein include a combination of chitosan, collagen type I, and carboxymethyl cellulose.

[0006] Aspects of the disclosure relate to the addition of a mucolytic bio-material to the compositions described herein to promote the breakdown of vaginal mucous. Vaginal mucous can block the uptake of a drug delivered locally into the targeted tissue, leading to lower efficacy. By simultaneously breaking down vaginal mucous while providing a therapy, drug delivery at the target site can be enhanced. In some embodiments, mucolytic agents are added to the device’s composition to promote mucus breakdown and clearance.

[0007] Aspects of the disclosure relate to a biocompatible device that mimics the extracellular matrix of normal tissue to form a porous scaffolding suitable for intravaginal drug delivery. This structure enhances the water retention of the device, facilitating the long-term potency and efficacy of the active therapeutic ingredients and any additional biomaterials. In some embodiments, this device enables the local, intravaginal delivery of active ingredients, biomaterials, and necessary excipients to treat diseases such as vaginitis, genitourinary syndrome, and other conditions. In one aspect, a porous scaffold device for insertion into a vaginal cavity of a mammal is disclosed. In some embodiments, the device includes, for example, chitosan, collagen, carboxymethyl cellulose, and an enzyme. In some embodiments, the device is formed in a cylindrical shape. In some embodiments, the device is comprises an elliptical circle. In some embodiments, the cylindrical shape has a length of approximately 0.5 cm to approximately 10 cm. In some embodiments, the cylindrical shape has a diameter of approximately 0.5 cm to approximately 3 cm. In some embodiments, the ratio of chitosan tocollagen to carboxymethyl cellulose is about 40:30:30 by weight. In some embodiments, the ratio of chitosan to collagen to carboxymethyl cellulose is about 50:25:25. In some embodiments, the ratio of chitosan to collagen to carboxymethyl cellulose is 60:20:20. In some embodiments, the enzyme comprises a DNase. In some embodiments, the DNase comprises DNase 1. In some embodiments, the chitosan is chitosan HC1. In some embodiments, the collagen is collagen type I. In some embodiments, the DNase 1 is included at a concentration of about 10 to about 100µg / ml mixed with respect to chitosan HC1, collagen type I, and carboxymethyl cellulose. In some embodiments, the enzyme is a mucolytic enzyme, and the device further comprises a pharmaceutically acceptable excipient and an active ingredient. In some embodiments, the device is a suppository.

[0008] In another aspect, a method of treating vaginal irritation or infection is disclosed. The method may include, for example, identifying an individual with a vaginal irritation or infection, and applying a suppository to the vaginal cavity of the individual. In some embodiments, the suppository includes chitosan, collagen, carboxymethyl cellulose, a mucolytic enzyme, a pharmaceutically acceptable excipient, and an active ingredient. In some embodiments, the irritation or infection is vaginitis.

[0009] In another aspect, a method of manufacturing a porous scaffold device for insertion into a vaginal cavity of a mammal is disclosed. In some embodiments, the method includes, for example, providing chitosan, collagen, carboxymethyl cellulose, and an enzyme to create a mixture; stirring the mixture to form a consistent liquid texture; pouring the liquid into a mold; freezing the liquid to form a porous scaffold device; lyophilizing the scaffold device; and sterilizing the scaffold device.

[0010] Aspects of the present disclosure relate to a porous scaffold device for use in administering a therapeutic compound or composition to a mammal. In some embodiments, the device comprises 1, 2, 3, or 4 of: a chitosan; a collagen; a carboxymethyl cellulose; an enzyme, or any combination thereof. In some embodiments, the therapeutic compound or composition is administered to the mammal by the device being inserted into the vaginal cavity. In some embodiments, the device comprises a cylindrical shape. In some embodiments, the device is a capsule. In some embodiments, the device is a cylinder. In some embodiments, the cylindrical shape has a length in a first direction of approximately 0.5 cm to approximately 10 cm, and a diameter of approximately 0.5 cm to approximately 3 cm. In some embodiments,a ratio of chitosan to collagen to carboxymethyl cellulose is about 40:30:30, about 50:25:25, or about 60:20:20 by weight. In some embodiments, the enzyme comprises a DNase and / or a mucolytic enzyme. In some embodiments, the DNase comprises DNase 1. In some embodiments, the chitosan comprises chitosan HC1. In some embodiments, the collagen comprises collagen type I. In some embodiments, the enzyme is included at a concentration of about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, or about 100 µg / ml, or any concentration that is between about 10 and about 100 µg / ml. In some embodiments, the device further comprises a pharmaceutically acceptable excipient and the therapeutic compound or composition. In some embodiments, the device is a suppository. In some embodiments, the device allows for the therapeutic compound or composition to be delivered past the vaginal mucus of the mammal, In some embodiments, the mammal is human. In some embodiments, the therapeutic compound or composition comprises a biological material and / or a chemical compound. In some embodiments, the biological material comprises at least 1, 2, 3, 4 or 5 of: an RNA, DNA, extracellular vesicle, cell, or any combination thereof. In some embodiments, the chemical compound comprises at least 1, 2, 3, 4, 5, 6, or 7 of: a small molecule, peptide, protein, antibody, ADS, lipid, lipid-derived molecule, or any combination thereof.

[0011] Aspects of the present disclosure relate to a method of treating a disease or disorder in a subject in need thereof. In some embodiments, the method comprises administering to the subject the device of any one of the embodiments of the present disclosure. In some embodiments, the device further comprises an at least one compound or composition that is therapeutically effective in treating the disease or disorder. In some embodiments, the device further comprises a pharmaceutically acceptable excipient. In some embodiments, the method comprises inserting the device into the vagina of the subject. In some embodiments, the disease or disorder comprises at least 1, 2, 3, 4, 5, or 6 of: vaginal atrophy, vaginal irritation, vaginal burning, urinary tract infection, vaginal infection, frequent urination, or any combination thereof. In some embodiments, the disease or disorder is vaginitis, vulvar cancer, vaginal cancer, or cervical cancer.

[0012] Aspects of the present disclosure relate to a method of manufacturing a porous scaffold device for use in administering a therapeutic compound or composition to a mammal. In some embodiments, the method comprises: providing chitosan, collagen,carboxymethyl cellulose, and an enzyme to create a mixture; stirring the mixture to form a consistent liquid texture; pouring the liquid into a mold; freezing the liquid to form a porous scaffold device; lyophilizing the scaffold device; and sterilizing the scaffold device.

[0013] In another aspect, a porous scaffold device for use in administering a therapeutic compound or composition to a mammal is disclosed. In some embodiments, the device comprises a chitosan, a collagen, a carboxymethyl cellulose, and an enzyme. In some embodiments, the therapeutic compound or composition is administered to the mammal by the device being inserted into the vaginal cavity. In some embodiments, the device is formed in a cylindrical shape. In some embodiments, the cylindrical shape has a length in a first direction of approximately 0.5 cm to 10 cm, a diameter of approximately 0.5 cm to 3 cm. In some embodiments, a ratio of chitosan to collagen to carboxymethyl cellulose is about 40:30:30, about 50:25:25, or about 60:20:20 by weight. In some embodiments, the enzyme comprises a DNase and / or a mucolytic enzyme. In some embodiments, the DNase comprises DNase 1. In some embodiments, the chitosan comprises chitosan HC1. In some embodiments, the collagen comprises collagen type I. In some embodiments, the enzyme is included at a concentration of about 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 pg / ml, or any concentration that is between about 10 and about 100 pg / ml. In some embodiments, the device further comprises a pharmaceutically acceptable excipient and the therapeutic compound or composition. In some embodiments, the device is a suppository. In some embodiments, the device allows for the therapeutic compound or composition to be delivered past the vaginal mucus of the mammal. In some embodiments, the mammal is human.

[0014] In another aspect, a method of treating a disease or disorder in a subject in need thereof is disclosed. In some embodiments, the method comprises administering to the subject the device of any one of the embodiments of the present disclosure, wherein the device further comprises at least one compound or composition that is therapeutically effective in treating the disease or disorder. In some embodiments, the device further comprises a pharmaceutically acceptable excipient. In some embodiments, the method comprises inserting the device into the vagina of the subject. In some embodiments, the disease or disorder comprises vaginal atrophy / irritation / burning, urinary tract infections, and frequent urination. In some embodiments, the disease or disorder is vaginitis, vulvar and vaginal cancer, or cervical cancer.

[0015] In another aspect, a method of manufacturing a porous scaffold device for use in administering a therapeutic compound or composition to a mammal is disclosed. In some embodiments, the method comprises providing chitosan, collagen, carboxymethyl cellulose, and an enzyme to create a mixture; stirring the mixture to form a consistent liquid texture; pouring the liquid into a mold; freezing the liquid to form a porous scaffold device; lyophilizing the scaffold device; and sterilizing the scaffold device.BRIEF DESCRIPTION OF THE DRAWINGS

[0016] FIG. 1A depicts a non-limiting example cartoon schematic of a vaginal suppository.

[0017] FIG. IB depicts a non-limiting example cartoon schematic of a vaginal rejuvenation kit comprising a vaginal suppository.

[0018] FIGs. 2A-2B depict non-limiting example scanning electron microscopy images of a scaffold structure’s surface (FIG. 2A) and its cross-section (FIG. 2B).

[0019] FIG. 3 depicts a non-limiting example quantification for the water absorption and retention capacity of the device over time in simulated conditions mimicking an open wound.

[0020] FIG, 4 depicts a non-limiting example of the quantification of cumulative, longitudinal drug release over time for a therapeutic at various device composition ratios,DETAWED DESCRIPTION

[0021] This disclosure provides, among other things, the design, materials, composition, and methods of manufacturing and using a novel, biocompatible, and degradable vaginal suppository capable of breaking down vaginal mucous and releasing the active ingredients, excipients, and other agents consistently over extended periods. The disclosure facilitates a more targeted and efficacious drug delivery than typical oral or intravenous means. In some embodiments, the ability of this device to effectively deliver therapies to the target tissue is furthered by infusing its structure with mucolytic agents capable of breaking down vaginal mucus surrounding the target tissue.

[0022] A device that is biocompatible, degradable, has a high drug-loading capacity, and can facilitate the long-term release of the therapeutic agent, provides benefits ofintravaginal drug delivery while addressing the limitations of current delivery’ methods. Such a device provides safe, convenient, and effective delivery of drugs while decreasing the risk of inflammation and irritation at the delivery site and reducing the risk of infection and procedural costs associated with other delivery methods. The capabilities of the device for high water absorption and retention allow for a higher drug-loading capacity compared to competitor products. Furthermore, the steady release of a drug from the device over days instead of hours allows for maximum efficacy of the drug.

[0023] The detailed description set forth herein is intended as a description of various configurations of the subject technology and is not intended to represent the only configurations in which the subject technology may be practiced. The detailed description provides specific details to facilitate an understanding of the subject technology. It will be apparent to those skilled in the art that the subject technology may be practiced without these specific details.Terms

[0024] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents, applications, published applications, and other publications are incorporated by reference in their entirety. In the event that there is a plurality of definitions for a term herein, those in this section prevail unless stated otherwise.

[0025] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0026] The articles “a” and “an” are used herein to refer to one or to more than one (for example, at least one) of the grammatical object of the article, unless the context dictates otherwise. By way of example, “an element” means one element or more than one element.

[0027] The terms “first,” “second,” and “third” used in combination with substances are intended to designate distinguishable features of similar substances and do not imply any particular order unless otherwise specified.

[0028] As used herein, the term “including” as well as other forms such as “includes” and “included” is not limiting.

[0029] As used herein, “approximately” and “about” mean that a number or other measure referred to as “approximately” or “about” comprises the recited number plus or minus1-10% of that recited number. For example, “about” 100 degrees can refer to a range of 95-100 degrees or as low as 99-101 degrees, depending on the context. Whenever it appears herein, a numerical range such as “1 to 20” refers to each integer in the given range, i.e., meaning only 1, only 2, only 3, etc., up to and including only 20.

[0030] Throughout this specification, unless the context requires otherwise, the words “comprise,” “comprises,” and “comprising” will be understood to imply the inclusion of a stated step or element or group of steps or elements but not the exclusion of any other step or element or group of steps or elements. By “consisting of” is meant including, and limited to, whatever follows the phrase “consisting of.” Thus, the phrase “consisting of” indicates that the listed elements are required or mandatory, and that no other elements may be present. By “consisting essential ly of,” it is meant including any elements listed after the phrase and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase “consisting essentially of’ indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they materially affect the activity or action of the listed elements.

[0031] The terms “individual”, “subject”, or “patient” as used herein have their plain and ordinary meaning as understood in light of the specification, and may include a human or a non-human mammal, e.g., a dog, a cat, a mouse, a rat, a cow, a sheep, a pig, a goat, a non-human primate, or a bird, e.g., a chicken, as well as any other vertebrate or invertebrate. The term “mammal” is used m its usual biological sense. Thus, it includes, but is not limited to, primates (including simians such as chimpanzees, apes, and monkeys), as well as humans, cattle, horses, sheep, goats, swine, rabbits, dogs, cats, rodents (including rats and mice), guinea pigs, and the like.

[0032] As used herein, the term “isolated” has its plain and ordinary meaning as understood in light of the specification, and may include to a substance and / or entity that has been (1) separated from at least some of the components with which it was associated when initially produced (whether in nature and / or in an experimental setting), and / or (2) produced, prepared, and / or manufactured by the hand of man. Isolated substances and / or entities may be separated from equal to, about, at least, at least about, not more than, or not more than about, 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about90%, about 95%, about 98%, about 99%, substantially 100%, or 100% of the other components with which they were initially associated (or ranges including and / or spanning the aforementioned values). In some embodiments, isolated agents are, are about, are at least, are at least about, are not more than, or are not more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, substantially 100%, or 100% pure (or ranges including and / or spanning the aforementioned values). As used herein, a substance that is “isolated” may be “pure” (e.g., substantially free of other components). As used herein, the term “isolated cell” may refer to a cell not contained in a multicellular organism or tissue.

[0033] The term “purity” of any given substance, compound, or material, as used herein, has its plain and ordinary meaning as understood in light of the specification and may include the actual abundance of the substance, compound, or material relative to the expected abundance. For example, the substance, compound, or material may be at least 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% pure, including all decimals in between. Purity may be affected by unwanted impurities, including but not limited to nucleic acids, DNA, RNA, nucleotides, proteins, polypeptides, peptides, amino acids, lipids, cell membrane, cell debris, small molecules, degradation products, solvent, carrier, vehicle, or contaminants, or any combination thereof. In some embodiments, the substance, compound, or material is substantially free of host cell proteins, host cell nucleic acids, plasmid DNA, contaminating viruses, proteasomes, host cell culture components, process-related components, mycoplasma, pyrogens, bacterial endotoxins, and adventitious agents. Purity can be measured using technologies including but not limited to electrophoresis, SDS-PAGE, capillary electrophoresis, PCR, rtPCR, qPCR, chromatography, liquid chromatography, gas chromatography, thin layer chromatography, enzyme-linked immunosorbent assay (ELISA), spectroscopy, UV-visible spectrometry, infrared spectrometry, mass spectrometry, nuclear magnetic resonance, gravimetry, or titration, or any combination thereof.

[0034] As used herein, the term “compound” has its usual meaning and thus can refer to a chemical or biological material. Non-limiting examples of a compound include an atom, small molecule, large molecule, peptide, protein, drug, or any combination thereof.

[0035] As used herein, the term “composition” has its usual meaning and thus can refer to a chemical or biological compound or substance, or a mixture or combination of twoor more such compounds or substances. In some embodiments, the composition comprises an atom, small molecule, large molecule, peptide, protein, salt, buffer, or any combination thereof. In some embodiments, the composition is formulated for a specific use, such as for administration to a subject.

[0036] As used herein, the terms “pharmaceutical composition” or “pharmaceutical formulation” may include a chemical or biological compound or substance, or a mixture or combination of two or more such compounds or substances, intended for use in the cure, treatment, prevention, or diagnosis of a disease or symptom.

[0037] As used herein, the term “pharmaceutical agent” has its usual meaning and thus can refer to a compound or composition with a known therapeutic function. In some embodiments, this function is used in the cure, treatment, prevention, or diagnosis of a disease or symptom. In some embodiments, a pharmaceutical agent comprises a drug. In some embodiments, a pharmaceutical agent comprises a composition that includes a drug.

[0038] As used herein, “carrier” may include a substance that serves as a vehicle for improving the efficacy of delivery or the effectiveness of a pharmaceutical composition, or both.

[0039] As used herein, “pharmaceutically acceptable” when used to define a carrier, whether diluent or excipient, may include a substance that is compatible with other ingredients in a formulation and does not exert deleterious effects to the recipient thereof. As used herein, “pharmaceutically acceptable” has its plain and ordinary meaning as understood in light of the specification and may include carriers, excipients, and / or stabilizers that are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed or that have an acceptable level of toxicity. A “pharmaceutically acceptable” “diluent,” “excipient,” and / or “carrier” as used herein have their plain and ordinary meaning as understood in light of the specification and may include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, that are compatible with administration to humans, cats, dogs, or other vertebrate hosts. Typically, a pharmaceutically acceptable diluent, excipient, and / or carrier is a diluent, excipient, and / or carrier approved by a regulatory agency of a Federal, a state government, or other regulatory agency, or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, including humans as well as non-human mammals, such ascats and dogs. The term diluent, excipient, and / or earner can refer to a diluent, adjuvant, excipient, or vehicle with which the pharmaceutical formulation is administered. Such pharmaceutical diluent, excipient, and / or carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin. Water, saline solutions, and aqueous solutions of dextrose and glycerol can be used as liquid diluents, excipients, and / or carriers, particularly for injectable solutions. Suitable pharmaceutical diluents and / or excipients include sugars, starch, glucose, fructose, lactose, sucrose, maltose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, salts, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol, and the like, A non-limiting example of a physiologically acceptable carrier is an aqueous pH-buffered solution. The physiologically acceptable carrier may also include one or more of the following: antioxidants, such as ascorbic acid, low molecular weight (less than about 10 residues) polypeptides, proteins, such as serum albumin, gelatin, immunoglobulins, hydrophilic polymers such as polyvinylpyrrolidone, amino acids, carbohydrates such as glucose, mannose, or dextrins, chelating agents such as EDTA, sugar alcohols such as glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, isomalt, maltitol, or lactitol, salt-forming counterions such as sodium, and nonionic surfactants such as TWEEN®, polyethylene glycol (PEG), and PLURONICS®. The formulation, if desired, can also contain minor amounts of wetting, bulking, emulsifying agents, or pH buffering agents. These formulations can take various forms, including solutions, suspensions, emulsions, and sustained-release formulations. The formulation should be suitable for the mode of administration.

[0040] The term “pharmaceutically acceptable salts” has its plain and ordinary meaning as understood in light of the specification and includes relatively non-toxic, inorganic and organic acid, or base addition salts of compositions or excipients, including, without limitation, analgesic agents, therapeutic agents, other materials, and the like. Examples of pharmaceutically acceptable salts include those derived from mineral acids, such as hydrochloric acid and sulfuric acid, as well as those derived from organic acids, including ethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid, among others. Examples of suitable inorganic bases for the formation of salts include the hydroxides, carbonates, and bicarbonates of ammonia, sodium, lithium, potassium, calcium, magnesium,aluminum, zinc, and the like. Salts may also be formed with suitable organic bases, including those that are non-toxic and strong enough to form such salts. For example, the class of such organic bases may include but are not limited to mono-, di-, and trialkylamines, including methylamine, dimethylamine, and triethylamine; mono-, di-, or trihydroxyalkylamines, including mono-, di-, and triethanolamine; amino acids, including glycine, arginine, and lysine; guanidine; N-methylglucosamine; N-methylglucamine; L-glutamine; N-methylpiperazine; morpholine; ethylenediamine; N-benzylphenethylamine; trihydroxymethyl aminoethane.

[0041] The terms “effective amount” or “effective dose” as used herein have their plain and ordinary meaning as understood in light of the specification, and may include an amount of a recited composition or compound that results in an observable effect. Actual dosage levels of active ingredients in an active composition of the presently disclosed subject matter can be varied so as to adm inister an am ount of the active composition or compound that is effective to achieve the desired response for a particular subject and / or application. The selected dosage level will depend upon a variety of factors, including, but not limited to, the activity of the composition, formulation, route of administration, combination with other drugs or treatments, severity of the condition being treated, and the physical condition and prior medical history of the subject being treated. In some embodiments, a minimal dose is administered, and the dose is escalated in the absence of dose-limiting toxicity to a minimally effective amount. Determination and adjustment of an effective dose, as well as evaluation of when and how to make such adjustments, are contemplated herein.

[0042] The terms “function” and “functional” as used herein have their plain and ordinary meaning as understood in light of the specification, and may include a property exhibited by a molecule, compound, or composition, including, for example, a biological, enzymatic, or therapeutic activity.

[0043] As used herein, the terms “treating” or “treatment” have their plain and ordinary meaning as understood in light of the specification, and may include an approach for obtaining beneficial or desired results in a subject’s condition, including clinical results. Beneficial or desired clinical results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of the extent of a disease, stabilizing (e.g., not worsening) the state of disease, prevention of a disease’s transmission or spread, delaying or slowing of disease progression, amelioration or palliation of the diseasestate, diminishment of the recurrence of disease, and remission, whether partial or total and whether detectable or undetectable. “Treating” and “treatment” as used herein also include prophylactic treatment. Treatment methods include administering to a subject a therapeutically effective amount of an active agent. The administering step may involve a single administration or a series of administrations. The compositions are administered to the subject in an amount and for a duration sufficient to treat the subject. The length of the treatment period depends on various factors, including the severity of the condition, the subject’s age and genetic profile, the concentration of the active agent, the activity of the compositions used in the treatment, or a combination of these factors. It will also be appreciated that the effective dosage of an agent used for the treatment or prophylaxis may increase or decrease over the course of a particular treatment or prophylaxis regimen. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. In some instances, chronic administration may be required.

[0044] As used herein, the term "therapeutic target" has its plain and ordinary meaning as understood in light of the specification and may include a gene or gene product that, upon modulation of its activity (e.g., by modulation of expression, biological activity, and the like), can provide for modulation of the disease phenotype. As used throughout, "modulation" refers to an increase or decrease in the indicated phenomenon (e.g., modulation of a biological activity refers to either an increase or a decrease in a biological activity).

[0045] The term “administering” includes contact with the skin, tissue, mucus, or fluid of a subject. It includes topical contact, administration as a suppository, intra vaginal, intravenous, intraperitoneal, intramuscular, intralesional, intratumoral, intrathecal, intranasal, or subcutaneous administration, or the implantation of a slow-release device, such as a mini-osmotic pump, to a subject. Administration can be by any route unless specifically stated, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intra-tumoral, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, and transdermal patches. By “co¬ administer,” it is meant that a first compound described herein is administered at the same time, just prior to, or just after the administration of a second compound described herein. Thepreferred administration of the present disclosure comprises contact with a subject’s reproductive glands or tissues, such as through transvaginal delivery and / or intravaginal delivery.

[0046] As used herein, “excipient” may include a pharmacologically inactive substance or compound that is formulated in combination with a pharmacologically active ingredient of a pharmaceutical composition, wherein an excipient may include a bulking agent, a filler, a diluent, or a product for drug solubility, drug absorption, or for modulating a pharmacokinetic property of an active ingredient of a pharmaceutical composition,

[0047] As used herein, “therapeutically effective amount” may include an amount or quantity of a pharmaceutical composition that elicits a desired clinical or biological response in a cell, a tissue, an organ, an animal or a human, or an amount or quantity that is clinically useful for reducing, eliminating, or otherwise affecting a disease, condition, or medical complication in a subject.

[0048] As used herein, “administration” (or other forms such as “administering”) may include an act of providing a substance or compound to a subject in need thereof.

[0049] As used herein, “treatment” may include an approach for providing beneficial or desired clinical or biological results, including but not limited to therapeutic benefit and / or prophylactic benefit. Therapeutic benefit refers to the eradication or alleviation of one or more physiological symptoms associated with an underlying disease or disorder.

[0050] The term “active ingredient” as used herein is to be given its ordinary and customary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning) and may include a component that confers a function. In some embodiments, the component has a direct or indirect effect on the cure, mitigation, treatment, diagnosis, or prevention of a disease or condition in the human or animal body.

[0051] The term “chitosan” as used herein is given its usual meaning and may include a linear polysaccharide comprising at least one D-glucosamine (deacetylated unit) and / or at least one N-acetyl-D-glucosamine (acetylated unit). In some embodiments, the chitosan comprises at least one β-(1→4)-linked D-glucosamine. In some embodiments, chitosan may be formed through the deacetylation of chitin, such as through contacting chitin with aqueous sodium hydroxide. In some embodiments, chitosan is a natural, biodegradable, and cationic polymer with use in the field of tissue engineering. In some embodiments,chitosan is modified. In some embodiments, chitosan is phosphorylated, thiolated, quatemized, or any combination thereof.

[0052] The term “collagen” as used herein is given its usual meaning and may include protein collagen. In some embodiments, the collagen is from human and / or mammalian sources. In some embodiments, the collagen comprises at least one of types I-XXVIII. In some embodiments, the collagen comprises at least one of types I, II, III, IV, or V. In some embodiments, collagen is modified. In some embodiments, collagen is in its natural protein form present in at least one of: bones, joints, muscles, skin, or any combination thereof. In some embodiments, collagen is in its monomer form. In some embodiments, collagen is a triple helix. In some embodiments, collagen is used as part of tissue regeneration in order to increase the proliferation of new cells,

[0053] The term “Carboxymethyl cellulose (CMC)” as used herein is a water-soluble derivative of cellulose, which is widely considered to be biocompatible and is commonly used in a range of biomedical and pharmaceutical applications. CMC exhibits characteristics such as non-toxicity, biodegradability, good hydrophilicity, low immunogenicity, and versatility in formulation, making it suitable as a cross-linking material.

[0054] “Biocompatible” as used herein is a broad term and is to be given its ordinary meaning to a person of ordinary skill in the art, and may include a material’s ability to perform an appropriate host response in a specific situation. In some embodiments, biocompatibility refers to a material’s interaction with a tissue or other part of a living body or system without causing undesirable or harmful effects, such as inflammation or irritation. In some embodiments, biocompatibility refers to the ability of a biomaterial to perform its desired function with respect to a medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response in that specific situation, and optimizing the clinically relevant performance of that therapy. In some embodiments, biocompatibility refers to the ability of a biomaterial to perform its desired function without causing a negative reaction with the surrounding tissue, or with the subject’s immune system.

[0055] A “biomaterial” as used herein is a broad term and is to be given its ordinary meaning to a person of ordinary skill in the art and may include a substance that has been engineered to interact with a biological molecule, cell, tissue, system, or individual. In someembodiments, a biomaterial is a biological protein, such as an enzyme. In some embodiments, the biomaterial has been engineered for medical purposes, such as treating, augmenting, repairing, or replacing tissue function in the body. In some embodiments, the biomaterial is naturally occurring. In some embodiments, the biomaterial is synthetic or is a modified variant of a naturally occurring material.

[0056] “Excipient” as used herein is a broad term and is to be given its ordinary meaning to a person of ordinary skill in the art, and may include to a substance that is added to a pharmaceutical composition to provide, without limitation, bulk, consistency, stability, binding ability, lubrication, disintegrating ability, etc., to the composition. A “diluent” is a nonlimiting example of a type of excipient. In some embodiments, an excipient refers to a pharmacologically inactive substance or compound that is formulated in combination with a pharmacologically active ingredient of a pharmaceutical composition, wherein an excipient may include a bulking agent, a filler, a diluent, or a product for drug solubility, drug absorption, or for modulating a pharmacokinetic property of an active ingredient of a pharmaceutical composition.

[0057] “Friability” as used herein may include a property of a material, substance, or composition to be broken, crumbled, or otherwise deteriorated, particularly by stress or contact with other materials.

[0058] “Pharmaceutically acceptable” as used herein is a broad term, and is to be given its ordinary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and may include compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for contact with tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complications commensurate with a reasonable risk / benefit ratio.

[0059] “Porosity” as used herein may include a property of a material, substance, or composition as the volume of interstitial space in that material relative to the total volume of that material.

[0060] “Scaffold” as used herein is a broad term and is to be given its ordinary meaning to a person of ordinary skill in the art (and is not to be limited to a special or customized meaning), and may include a material or structure that aids in support and / or interaction of other molecules, compositions, drugs cells, tissues, systems, or any combinationtliereof. In some embodiments, a scaffold comprises a porous material and / or a porous structure. In some embodiments, the scaffold is suitable for structural support and / or providing an environment conducive to cell activity. A non-limiting example of a scaffold includes a material or structure that mimics an extracellular matrix in biological tissue or organ systems.

[0061] “Water absorption” as used herein is the capacity for water to be taken up, soaked, or absorbed into a material, cell, tissue, system, or structure. In some embodiments, water absorption can be measured as the ability of a material, cell, tissue, system, or structure to absorb and retain water over a period of time.Materials and composition

[0062] As described herein, a vaginal suppository was designed using biocompatible materials that are non-toxic and lead to reduced levels of inflammation and irritation during and following application. In some embodiments, biocompatible materials comprise at least one chitosan, collagen, carboxymethyl cellulose, or any combination thereof. In some embodiments, the biocompatible materials provide non-toxic interactions with vaginal tissue, leading to reduced levels of inflammation and irritation. Chitosan is a natural, biodegradable, and cationic polymer that has demonstrated use in the field of tissue engineering. It does not typically induce inflammation, irritation, or similar side effects in the area of application. Similarly, collagen is a naturally occurring protein that is present normally in bones, muscles, and skin. Collagen is the primary structural component of human skin and has been shown to promote tissue regeneration by stimulating the proliferation of new cells. Carboxymethyl cellulose (CMC) is widely regarded as biocompatible and has been successfully utilized in various biomedical and pharmaceutical applications. CMC is nontoxic, biodegradable, has desirable hydrophilicity, and low immunogenicity. Because CMC has proven versatility in formulation, it has substantial use as a cross-linking material. In some embodiments, the chitosan is derived from chitin sourced from the exoskeletons of crustaceans or insects. In some embodiments, the chitosan is derived from chitin sourced from the cell walls of fungi. In some embodiments, the collagen is sourced from animal byproducts, such as the hides, skin, or bones from bovine, porcine, avian, or marine animal processing. In some embodiments, the carboxymethyl cellulose is sourced from agricultural byproducts, including but not limited to wood pulp, cotton, flax, hemp, or other natural fibers, or agricultural products such as corn or rice. In some embodiments, the scaffold structure comprising the device iscomposed of about 40:60, about 50:50, or about 60:40 chitosan to carboxymethyl cellulose ratio by weight, or any ratio between the aforementioned amounts. In some embodiments, the scaffold structure comprising the device is made up of a composition of about 40:30:30, about 50:25:25, or about 60:20:20 chitosan to collagen to carboxymethyl cellulose by weight, or any ratio between the aforementioned amounts. In some embodiments, additional biocompatible cross-linking agents are added to these concentrations to further promote the biodegradability of the resulting structure. For example, some embodiments include the addition of P-glycerol phosphate, glutaraldehyde, dialdehyde starches, tannic acids, genipin, or carbodiimides to the composition to facilitate cross-linking,

[0063] In some embodiments, the resulting structure has a spongy consistency with an overall diameter ranging from about 0.5 cm to about 3 cm. For example, in some embodiments the diameter of the devices is about 0.5 cm, about 0.6 cm, about 0.7 cm, about 0.8 cm, about 0.9 cm, about 1.0 cm, about 1.1 cm, about 1.2 cm, about 1.3 cm, about 1.4 cm, about 1,5 cm, about 1.6 cm, about 1.7 cm, about 1.8 cm, about 1.9 cm, about 2.0 cm, about 2,1 cm, about 2.2 cm, about 2.3 cm, about 2,4 cm, about 2.5 cm, about 2.6 cm, about 2.7 cm, about 2.8 cm, about 2.9 cm, about 3.0 cm, or a range defined by any two numbers therein.

[0064] In some embodiments, the resulting device features cross-linking bridges with a spongy texture on both its surface and cross-section. As described herein, the pores of this structure are between about 10 pm and about 110 pm. For example, in some embodiments, the pore size is about 10 pm, about 20 pm, about 30 pm, about 40 pm, about 50 pm, about 60 pm, about 70 pm, about 80 pm, about 90 pm, about 100 pm, about 110 pm, or a range defined by any two of these values. In some embodiments, the resulting pore structure of the device can facilitate the passage of extracellular vesicles ranging from about 20 nm to about 10 pm m diameter. For example, in some embodiments the pore structure of the device can facilitate vesicles of about 0.02 pm, 0.03 pm, 0.04 pm, 0.05 pm, 0.06 pm, 0.07 pm, 0.08 pm, 0.09 pm, 0.1 pm, 0.11 pm, 0.12 pm, 0.13 pm, 0.14 pm, 0.15 pm, 0.16 pm, 0.17 pm, 0.18 pm, 0.19 pm, 0.2 pm, 0.21 pm, 0.22 pm, 0.23 pm, 0.24 pm, 0.25 pm, 0.26 pm, 0.27 pm, 0.28 pm, 0.29 pm, 0.3 pm, 0.31 pm, 0.32 pm, 0.33 pm, 0.34 pm, 0.35 pm, 0.36 pm, 0.37 pm, 0.38 pm, 0.39 pm, 0.4 pm, 0.41 pm, 0.42 pm, 0.43 pm, 0.44 pm, 0.45 pm, 0.46 pm, 0.47 pm, 0.48 pm, 0.49 pm, 0.5 pm, 0.51 pm, 0.52 pm, 0.53 pm, 0.54 pm, 0.55 pm, 0.56 pm, 0.57 pm, 0.58 pm, 0.59 pm, 0.6 pm, 0.61 pm, 0.62 pm, 0.63 pm, 0.64 pm, 0.65 pm, 0.66 pm, 0.67 pm, 0.68 pm, 0.69 pm,0.7 pm, 0.71 pm, 0.72 pm, 0.73 pm, 0.74 pm, 0.75 pm, 0.76 pm, 0.77 pm, 0.78 pm, 0.79 pm, 0.8 pm, 0.81 pm, 0.82 pm, 0.83 pm, 0.84 pm, 0.85 pm, 0.86 pm, 0.87 pm, 0.88 pm, 0.89 pm, 0.9 pm, 0.91 pm, 0.92 pm, 0.93 pm, 0.94 pm, 0.95 pm, 0.96 pm, 0.97 pm, 0.98 pm, 0.99 pm, 1 pm, 1.1 pm, 1.2 pm, 1.3 pm, 1.4 pm, 1.5 pm, 1.6 pm, 1.7 pm, 1.8 pm, 1.9 pm, 2 pm, 2.1 pm, 2.2 pm, 2.3 pm, 2.4 pm, 2.5 pm, 2.6 pm, 2.7 pm, 2.8 pm, 2.9 pm, 3 pm, 3.1 pm, 3.2 pm, 3.3 pm, 3.4 pm, 3.5 pm, 3.6 pm, 3.7 pm, 3.8 pm, 3.9 pm, 4 pm, 4.1 pm, 4.2 pm, 4.3 pm, 4.4 pm, 4.5 pm, 4.6 pm, 4.7 pm, 4.8 pm, 4.9 pm, 5 pm, 5.1 pm, 5.2 pm, 5.3 pm, 5.4 pm, 5.5 pm, 5.6 pm, 5.7 pm, 5.8 pm, 5.9 pm, 6 pm, 6.1 pm, 6,2 pm, 6.3 pm, 6.4 pm, 6.5 pm, 6,6 pm, 6.7 pm, 6.8 pm, 6,9 pm, 7 pm, 7.1 pm, 7,2 pm, 7.3 pm, 7.4 pm, 7.5 pm, 7.6 pm, 7,7 pm, 7.8 pm, 7.9 pm, 8 pm, 8.1 pm, 8.2 pm, 8.3 pm, 8.4 pm, 8.5 pm, 8.6 pm, 8.7 pm, 8.8 pm, 8,9 pm, 9 pm, 9.1 pm, 9.2 pm, 9.3 pm, 9.4 pm, 9,5 pm, 9,6 pm, 9.7 pm, 9.8 pm, 9,9 pm, about 10 µm in diameter, or a diameter within a range defined by any two numbers therein. In some embodiments, the resulting pore structure of the device can facilitate the delivery of living cells, such as stem cells, ranging from 10 pm to 140 pm in diameter. For example, some embodiments can facilitate the delivery of cells about 10 pm, 11 pm, 12 pm, 13 pm, 14 pm, 15 pm, 16 pm, 17 pm, 18 pm, 19 pm, 20 pm, 21 pm, 22 pm, 23 pm, 24 pm, 25 pm, 26 pm, 27 pm, 28 pm, 29 pm, 30 pm, 31 pm, 32 pm, 33 pm, 34 pm, 35 pm, 36 pm, 37 pm, 38 pm, 39 pm, 40 pm, 41 pm, 42 pm, 43 pm, 44 pm, 45 pm, 46 pm, 47 pm, 48 pm, 49 pm, 50 pm, 51 pm, 52 pm, 53 pm, 54 pm, 55 pm, 56 pm, 57 pm, 58 pm, 59 pm, 60 pm, 61 pm, 62 pm, 63 pm, 64 pm, 65 pm, 66 pm, 67 pm, 68 pm, 69 pm, 70 pm, 71 pm, 72 pm, 73 pm, 74 pm, 75 pm, 76 pm, 77 pm, 78 pm, 79 pm, 80 pm, 81 pm, 82 pm, 83 pm, 84 pm, 85 pm, 86 pm, 87 pm, 88 pm, 89 pm, 90 pm, 91 pm, 92 pm, 93 pm, 94 pm, 95 pm, 96 pm, 97 pm, 98 pm, 99 pm, 100 pm, 101 pm, 102 pm, 103 pm, 104 pm, 105 pm, 106 pm, 107 pm, 108 pm, 109 pm, 110 pm, 111 pm, 112 pm, 113 pm, 114 pm, 115 pm, 116 pm, 117 pm, 118 pm, 119 pm, 120 pm, 121 pm, 122 pm, 123 pm, 124 pm, 125 pm, 126 pm, 127 pm, 128 pm, 129 pm, 130 pm, 131 pm, 132 pm, 133 pm, 134 pm, 135 pm, 136 pm, 137 pm, 138 pm, 139 pm, about 140 pm in diameter, or a diameter within a range defined by any two numbers therein.

[0065] As described herein, the resulting structure exhibits several physical properties that are crucial for effective drug delivery. For example, some embodiments of this disclosure offer ideal porosity, friability, water absorption, and retention capacity, as well as the ability to release the combined biomaterial into the local tissue.

[0066] To absorb and transport extracellular vesicles, living cells, and other materials within its scaffolds and ensure vaginal rejuvenation and healing, the device must have adequate water absorption and retention. As described herein, the resulting structure of the device forms a strong ionic polyelectrolyte complex containing many ionized carboxylic groups, which results in the ability to absorb high amounts of water through interactions with the water’s hydroxyl group. The resulting structure exhibits a strong swelling index score that decreases slowly over periods of up to 30 days post-absorption, demonstrating a suitable water absorption capacity and retention for vaginal drug delivery. As described herein, the resulting product can gradually release active ingredients and biomaterials sustainably for up to 60 hours. For example, some embodiments in this disclosure are capable of releasing therapeutics in a sustained manner for up to 60 hours. This extended release without an initial burst release following insertion is ideal for breaking down vaginal mucous, promoting intravaginal drug delivery, and prolonged vaginal healing.Non-limiting Example Methods for Making a Device or Kit

[0067] Some aspects of the present disclosure relate generally to a method of making and / or manufacturing a device of any one of the embodiments of the present disclosure. In some embodiments, the device is a porous scaffold. In some embodiments, the device has use in administering a compound or composition to a subject. In some embodiments, the method comprises creating a mixture comprising a chitosan, a collagen, a carboxymethyl cellulose (CMC), and an enzyme. In some embodiments, the mixture is liquified, then poured into a mold. In some embodiments, the mixture is then solidified, thus forming the device of any one of the embodiments of the present disclosure. Non-limiting examples of the solidification process includes freezing and / or adding a solidifying agent. In some embodiments, the device is sterilized and / or lyophilized prior to its use.

[0068] In some embodiments, the mixture comprises a natural or a modified chitosan. In some embodiments, the mixture comprises chitosan HC1. In some embodiments, the mixture comprises a natural or a modified collagen. In some embodiments, the mixture comprises at least 1, 2, 3, 4, or 5 types of collagen. In some embodiments, the mixture comprises collagen type I. In some embodiments, the mixture comprises a natural or a modified CMC. In some embodiments, the mixture comprises a natural or a modified enzyme. In some embodiments, the mixture comprises at least 1, 2, 3, 4, or 5 types of enzymes. In someembodiments, the enzyme has activity in breaking mucous. In some embodiments, the enzyme is a mucolytic enzyme. In some embodiments, the enzyme has activity in breaking apart vaginal mucous. In some embodiments, the enzyme has DNase activity. In some embodiments, the enzyme is a member of the DNase I or DNase II family. In some embodiments, the enzyme is a DNase I, DNase 1L1, DNase 1L2, and DNase 1L3, DNase II α, DNase II β, N-acetylcysteme, carbocisteine, or dornase a.

[0069] In some embodiments, the mixture comprises chitosan to CMC at a ratio that is about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, or any value that is between about 5:1 and about 1:5 by weight. In some embodiments, the mixture comprises chitosan to collagen at a ratio that is about 5: 1, about 4: 1, about 3:1, about 2: 1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, or any value that is between about 5:1 and about 1:5 by weight In some embodiments, the mixture comprises collagen to CMC at a ratio that is about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, or any value that is between about 5:1 and about 1:5 by weight. In some embodiments, the mixture comprises chitosan to collagen to CMC at a ratio that is about 40:30:30, about 50:25:25, about 60:20:20, or any integer that is between about 40:30:40 and about 60:20:20 by weight. In some embodiments, the mixture comprises chitosan to collagen to CMC at a ratio that is about 5:1:1, about 4:1:1, about 3:1:1, about 2:1:1, about 1: 1: 1, or any value that is between about 5:1:1 and about 1:1:1.

[0070] In some embodiments, the enzyme is included in the mixture at a concentration of about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100 µg / ml, or any concentration that is between about 10 and about 100 µg / ml.

[0071] Aspects of the present disclosure relate to administering the device to a subject m need thereof. In some embodiments, the device is administered inside the subject. The device may be molded into any shape that is appropriate for its administration to the subject. For example, in an embodiment in which the device is intended for intravaginal delivery', the device may be an appropriate size and shape for fitting the subject intravaginally. In some embodiments, the device is a capsule and / or is cylindrical in shape. In some embodiments, the size and shape of the device is adjusted based on the subject.

[0072] In some embodiments, the device is a cylindrical shape comprising a first diameter in a first direction, and a second diameter in a second direction that is perpendicular to the first direction. In some embodiments the ratio of the first diameter to the second diameter is about 0.01: 15, about 0.05: 15, about 0.1: 15, 0.5: 3, about 0.5: 2, about 0.5: 1, about 1: 1, about 1: 0.5, about 2: 0.5, about 3: 0.5, about 4: 0.5, about 5: 0.5, about 6: 0.5, about 7: 0.5, about 8: 0.5, about 9: 0.5, about 10: 0.5, about 11: 0.5, about 12: 0.5, about 13: 0.5, about 14: 0.5, about 15: 0.5, about 15: 0.01, or any value that is between about 0.01: 15 and about 15: 0.01. In some embodiments, the first diameter is about 0.01 cm, about 0.05 cm, about 0,1 cm, about 0.5 cm, about 1.0 cm, about 1,5 cm, about 2 cm, about 2.5 cm, about 3 cm, about 3,5 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about 9 cm, about 10 cm, about 11 cm, about 12 cm, about 13 cm, about 14 cm, about 15 cm, or any value that is between about 0,01 cm and about 15 cm. In some embodiments, the first diameter is about 0.5 cm to about 10 cm. In some embodiments, the second diameter is about 0,01 cm, about 0.05 cm, about 0.1 cm, about 0,5 cm, about 1.0 cm, about 1,5 cm, about 2 cm, about 2.5 cm, about 3 cm, about 3.5 cm, about 4 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about 9 cm, about 10 cm, about 11 cm, about 12 cm, about 13 cm, about 14 cm, about 15 cm, or any value that is between about 0.01 cm and about 15 cm. In some embodiments, the second diameter is about 0.5 cm to about 3 cm.

[0073] In some embodiments, the device is degradable. In some embodiments, the device is biocompatible. In some embodiments, the device has use as a suppository.

[0074] In some embodiments, the device is administered to a subject at least 1, 2, 3, 4, or 5 times. In some embodiments, the device is removed from the subject after delivering a therapeutic agent. In some embodiments, the device is allowed to degrade inside the subject.

[0075] In some embodiments, the device is used to administer a therapeutic agent (also referred to herein as a therapeutic compound or therapeutic composition) to a subject in need thereof. In some embodiments, the subject has a disease, disorder, or condition in need of treatment. In some embodiments, the therapeutic agent is effective against the disease, disorder, or treatment. In some embodiments, the therapeutic agent comprises a small molecule, peptide, protein, nucleic acid, drug, salt, vesicle, cell, or population of cells. In some embodiments, the therapeutic agent comprises a small molecule, peptide, protein, antibody, ADS, lipid, or lipid-derived molecule. In some embodiments, the therapeutic agent comprisesan exosome. In some embodiments, the therapeutic agent comprises an exosomes derived from mesenchymal stem cells (MSCs).

[0076] Exosomes derived from MSCs have demonstrated effectiveness in treating, and in some cases even curing, genitourinary’ syndrome of menopause. Exosomes derived from huCMSC significantly increase the viability of human vaginal epithelial VK2 cells and primary' human vaginal fibroblast cells, and reduce their apoptosis in vitro. Exosomes have also been shown to increase vaginal fibroblast contraction and collagen secretion in vitro. Exosomes vaginal delivery' significantly increases the thickness of the vaginal epithelium layer and the expression of markers for proliferation and angiogenesis in the post-menopausal rat model.

[0077] Some embodiments of the present disclosure relate to a kit comprising the delivery' device and a diluent. In some embodiments, the kit further comprises a lyophilized exosome with therapeutic use.Non-limiting Example Uses

[0078] Aspects of the present disclosure relate to uses for the device. In some embodiments, the device of any one of the embodiments of the present disclosure has therapeutic use. In some embodiments, the device has use in administering a therapeutic compound or composition to a subject in need thereof. In some embodiments, the device has use in an immediate administration of the therapeutic compound or composition. In some embodiments, the device has use in a delayed administration of the therapeutic agent. In some embodiments, the device is inserted into a subject. In some embodiments, the device has use as a suppository. In some embodiments, the device has use as a vaginal suppository.

[0079] In some embodiments of the present disclosure, the device is inserted into a vaginal cavity of the subject. In some embodiments, the device further comprises a therapeutic compound or composition. In some embodiments, the device has use in mediating the delivery of the therapeutic compound or composition past the vaginal mucus of the subject. In some embodiments, the device mediates the delivery by affecting the pH, and / or the thickness of the vaginal mucus.

[0080] The therapeutic compound or composition may be any substance with beneficial properties to the subject. In some embodiments, it treats a disease, disorder, or preexisting condition.

[0081] Aspects of the present disclosure relate to a method of treating a subject in need thereof, the method comprising administering to the individual the device of any one of the embodiments of the present disclosure, wherein the device further comprises a therapeutic compound or composition that is effective in treating the subject. In some embodiments, the subject is mammalian and / or human. In some embodiments, the subject is female. In some embodiments, the subject has reached puberty'. In some embodiments, the subject is pre¬ menopausal. In some embodiments, the subject has reached menopause. In some embodiments, the subject is post-menopausal. In some embodiments, the subject has a cancer and / or a tumor.

[0082] In some embodiments, the device has use in administering a therapeutic compound or composition effective against a disease, disorder, or pre-existing condition in a subject, In some embodiments, the disease, disorder, or pre-existing condition is linked to the genitals. In some embodiments, the disease, disorder, or pre-existing condition is vaginal atrophy and / or vaginal dryness. In some embodiments, the disease, disorder, or pre-existing condition is genitourinary syndrome of menopause (GSM). In some embodiments, the subject has menopause. In some embodiments, the therapy is effective in restoring the vaginal lining thickness, vaginal elasticity, vaginal microenvironment, or any combination thereof.EXAMPLES

[0083] The following examples are given for the purpose of illustrating various embodiments of the disclosure and are not meant to limit the present disclosure in any fashion. One skilled in the art will readily appreciate that the present disclosure is well adapted to carry out the objects and obtain the ends and advantages mentioned and those objects, ends, and advantages inherent herein. Changes therein and other uses which are encompassed within the spirit of the disclosure, as defined by the scope of the claims, will occur to those skilled in the art. Examples of some embodiments containing specific biomaterials, manufacturing methods for these embodiments, and testing these embodiments for desired physical properties and device efficacy are illustrative and not intended to limit the present disclosure in any fashion.Example 1: Bio-Material(s)

[0084] A vaginal suppository was designed using biocompatible materials that are non-toxic and lead to reduced levels of inflammation and irritation during and following application (FIG. 1A). As described herein, the structure of this suppository can be combined with known biomaterials, such as mucolytic enzymes, to produce a biocompatible device thatalso facilitates the necessary breakdown of vaginal mucous to successfully increase the delivery of drugs to the target tissue. For example, some embodiments of this disclosure have the addition of human recombinant DNase enzymes to the structural components of the device. Some embodiments include biomaterials of the DNase I family, including but not limited to DNase I, DNase 1L1, DNase 1L2, and DNase 1L3. Other embodiments include biomaterials of the DNase II family, including but not limited to DNase II α and DNase II β. Other embodiments envisioned by this disclosure include mucolytic enzymes with demonstrated ability to facilitate the breakdown of thick vaginal mucous, such as N-acetylcysteine, carbocisteine, or dornase a.

[0085] DNase I is an enzyme that breaks down extracellular DNA (eDNA), a major component of thick, sticky mucus, especially during inflammation or infection. The optimal working pH range is 6.5 to 8.0, Human recombinant DNase 1 enzyme has been FDA-approved since the 1990s for clinical use, primarily for treating cystic fibrosis (CF). DNase 1 helps break down extracellular DNA in the thick mucus that accumulates in the lungs of CF patients, making it easier to clear and thus improving lung function in these patients. The pH of a CF lung ASL (airway surface liquid) is often reduced to ~6.5 or lower. In vaginal mucus (like in the lung), extracellular DNA is released from: (1) dead cells, (2) neutrophils, (3) bacterial biofilms, or any combination thereof. The released DNAs in turn increase the viscosity and stickiness of the mucus.

[0086] For menopausal and postmenopausal women, due to reduced estrogen levels, the vaginal lining thins and lactobacilli decrease, resulting in a less acidic pH, typically ranging from 4.5 to 6.5, and sometimes higher. Some embodiments disclosed herein utilize human recombinant DNase 1 as an adjunct to break down the biofilm of mucus inside the vagina, thereby enhancing the efficacy of drug delivery.

[0087] DNases, such as DNase 1, are being investigated in the context of inflammation and infection, where extracellular DNA or neutrophil extracellular traps (NETs) contribute to disease pathology. DNases are being investigated as therapeutic options in gynecological contexts, including conditions such as bacterial vaginosis and other types of vaginitis. DNases can facilitate the breakdown of extracellular DNA (eDNA), which contributes to the formation of thicker, stickier vaginal mucus associated with inflammation or infection, and less acidic conditions. eDNA can come from a number of sources in the vagina,including: (1) dead cells, (2) neutrophils, (3) bacterial biofilms. DNases and other biomaterials can be added directly to chitosan, collagen, and carboxymethyl cellulose (CMC) mix before lyophilization.Example 2: Methods of manufacturing

[0088] In some aspects, the disclosure provides a method for manufacturing a biocompatible structure by combining natural, biodegradable, and biocompatible components as major materials in device construction. The resulting device is nontoxic and decreases the likelihood of inflammation while promoting the proliferation of new cells at the site of delivery. In other aspects, the disclosure provides a method of integrating a biomaterial capable of breaking down the thick vaginal mucous into the structure of the described device. For example, in some embodiments, mucolytic enzymes, including but not limited to DNases, are incorporated into the biocompatible materials of the suppository to enable the device to break down mucus during insertion.

[0089] In one embodiment, DNase I with a concentration of 10-100 pg / ml was mixed with: chitosan HC1 and the cross-linking agents collagen type I and carboxymethyl cellulose (all from Sigma Aldrich, USA) to prepare scaffolds with ratios of chitosan to crosslinking agent as follows: 40:30:30 by weight, the solution containing the cross-linking agent was added portion wise to chitosan HC1 and DNase solution during stirring on magnetic stirrer at 200 rpm (IKA® C-MAG HS10 digital, Germany) to avoid formation of sticky masses. The resulting turbid mixture was poured into molds and placed in an ultra-low freezer at -80°C for 48 hours. Then the mixture was lyophilized using a Christ freeze dryer (ALPHA 2-4 LD plus, Germany) for 24 hours. All scaffolds were then sterilized by gamma radiation at 10 kGy (1.88 kGy / h) to prevent any contamination.Example 3: Preparation of Scaffolds

[0090] The scaffolds were prepared from a mixture of chitosan HC1 and cross¬ linking agents (B-glycerolphosphate, collagen type I, and carboxymethyl cellulose). The resulting scaffolds comprised weight ratios of chitosan to cross-linking agent as follows: 40:30:30.

[0091] DNase 1 was added portion- wise to the chitosan HC1 solution during stirring on a magnetic stirrer at 200 rpm (IKA C-MAG HS 10 digital, Germany ) to prevent theformation of sticky masses. The resulting turbid mixture was poured into cylindrical molds (5 cm long and 0.5 cm in diameter) and placed in a refrigerator at -80 °C for 48 hours. Then, the mixture was lyophilized using a Christ freeze dryer for 24 h. The physical characteristics of the scaffolds were then tested.Example 4: Physical properties

[0092] As described herein, some embodiments can be manufactured, packaged, transported, and stored until they are applied to patients. The resulting structure of some embodiments loses less than 0.6% of its original weight during standard friability testing, simulating the necessary durability for this type of device.

[0093] The sterilized scaffolds were then tested for their porosity, friability’, in vitro drug release, water absorption, and water retention capacity.

[0094] 1) Porosity: The shape of the freeze-dried scaffold using collagen and carboxymethyl cellulose as cross-linking agents had a definite 3-dimensional shape, flat surface, and spongy porous structure. Scaffolds prepared revealed a definite cylindrical shape with an off-white color and a spongy consistency, with a diameter ranging between 0.5 and 3.0 cm. Morphological examination of the scaffold using scanning electron microscopy (SEM) revealed the formation of networks and cross-linking bridges, resulting in an interconnected porous structure (50-100 pm) with a spongy shape, as evident in both surface and cross-sectional images. The suitable scaffold pore size can hold extracellular vesicles (EVs), ranging from 10 nm to 5 pm, and living cells, such as stem cells, ranging from 10 to 140 pm. Such a pore size is suitable for EV adhesion and cell proliferation, as well as nutrient exchange. The formation of a highly porous and spongy scaffold was facilitated by the lyophilization process during scaffold preparation.

[0095] 2) Friability: The tablet friability’ test was done for the fabricated scaffolds to predict their physical strength during handling, packaging, and transportation until they reached the patient. The drum of the apparatus was adjusted to rotate at a speed of 25 rpm (The United States Pharmacopoeia, 2016), and the percentage weight loss for the scaffolds was calculated using the following equation:, Initial weight — Final weiqhtWeight Loss (%) = - - - - - - - x 100Initial weight

[0096] Weight loss of scaffolds should be at least about 1% to be accepted; all the tested scaffolds passed the friability test study (% weight loss <0.6%).

[0097] 3) Water absorption and retention capacity: The swelling index reflects the ability of the scaffolds to absorb and carry nutrients and metabolites to living cells inside the scaffolds, such as stem cells. Also, fluid retention in the scaffold is very important for vagina rejuvenation and healing.

[0098] The dry scaffolds were weighed (W0) and placed over a sponge saturated with phosphate saline at pH 7.4. The samples were incubated for a month at 37°C and their weights were measured (Wl) at definite time intervals. The water absorption capacity was calculated by measuring the weight of water absorbed by the scaffold at definite time intervals until the maximum absorbed weight was reached. The water absorption capacity was calculated using the above equation, where WS is the water absorption capacity of the scaffold (%), Wl is the weight of the swollen scaffold at a definite time (g), and W0 is the weight of the dry scaffold (g).

[0099] The chitosan / collagen / carboxymethyl cellulose scaffolds were found to have a water absorption capacity of 1554% (FIG. 3). The interaction of carboxymethyl cellulose with chitosan forms a strong ionic polyelectrolyte complex, which contains many ionized carboxylic groups, allowing it to interact with the hydroxyl groups of water and absorb a high amount of water. This scaffold revealed the low drop in water absorption capacity from 1554% during the first days to 531% after 14 days, and 444% after 30 days. This example scaffold showed high water absorption capacity and low disintegration during the study period; it also showed suitable water absorption capacity and a gradual decrease in water content, offering ideal characteristics for vaginal drug delivery. In other embodiments, the scaffolds were found to have water absorption capacity values ranging from 396% to 2993%, depending on the combination of scaffold materials described above.

[0100] The shape of the freeze-dried scaffold, which utilizes collagen and carboxymethyl cellulose as cross-linking agents, exhibits a definite 3-dimensional structure, a flat surface, and a spongy porous texture. Prepared scaffolds exhibit a distinct cylindrical shape, characterized by an off-white color and spongy consistency, with a diameter ranging from about 0.5 to about 3.0 cm. Morphological examination of the scaffold using scanning electron microscopy (SEM) reveals the formation of networks and cross-linking bridges,resulting in an interconnected porous structure with a diameter of between 50 and 100 pm and a spongy texture on both the surface and cross-section (FIGs. 2A-2B). The suitable scaffold pore size can hold extracellular vesicles ranging from about 10 nm to about 5 pm in size, as well as living cells, such as stem cells, ranging from about 10 to about 140 pm m size. Thus, the pore size is suitable for EVs and living cells’ adhesion and cell proliferation, as well as nutrient exchange.Example 5: Administrative Kit

[0101] The scaffold device can be combined with additional adjuncts to form a vaginal rejuvenation kit, which consists of the device and necessary’ adjuncts (FIG. IB). In some embodiments, adjuncts include a diluent and a lyophilized powder, which can be stored in a refrigerator or at room temperature.Example 6: Assays for safety and efficacy

[0102] As described herein, some embodiments are capable of reducing both the thickness of vaginal mucosa and inflammatory symptoms in an animal model. For example, some embodiments, when suitably applied, can reduce the thickness of the mucosa, redness, and swelling, decrease discharge, and reduce inflammatory conditions, thereby increasing vaginal health scores in adult female Wistar rats in a bilateral ovariectomy model.Example 7: In-vitro biomaterials release assay:

[0103] The prepared scaffolds were tested for drug release using a Franz diffusion cell apparatus (Automated Microette Plus; Hanson Research, USA). The scaffolds were placed in the donor compartment, while an isotonic phosphate buffer solution with a pH of 7.4 was placed in the receptor compartment. The temperature was adjusted to 37°C, the stirring rate to 200 rpm, and a certain amount of double-stranded DNA substrates was added. Samples (2 mL) were taken at specific time intervals and diluted to measure the DNase I concentration using a spectrophotometer apparatus (Shimadzu, UV- 1800, Japan) at 260 nm, due to the hydrolysis of DNA.

[0104] The DNase 1 release profiles from the scaffolds showed a gradual release of the drug from the scaffolds for up to 60 hours without any distinct initial burst release (FIG.4). Such sustained release profiles would promote a gradual vagina healing process and areideal for the disclosed device. Generally, all the release data for the scaffolds showed the best fit to the Higuchi equation, and the time required for 90% of the drug release (t90) varied between 37.32 and 53.12 hours. The mean dissolution time values ranged between 12.80 and 21.20 hours. The scaffolds showed similar release parameters (MDT and t90 values; p > 0.05), where scaffold composition generally did not affect these parameters due to their highly similar porous structures (88% to 91%).Example 8: In-vivo animal model safety' and efficacy assay:

[0105] Ail scaffolds used in our in vivo study were sterilized by gamma radiation at 10 kGy (1.88 kGy / h) to ensure safe implantation and prevent contamination. The sterilized scaffolds were retested for their porosity, friability, in vitro drug release, water absorption, and water retention capacity. No significant differences were observed in the data obtained before and after sterilization (p < 0.05).

[0106] Adult female Wistar rats (SPF class, 250-300 g, Subjects) were established as a bilateral ovariectomy (OVX) animal model. The presence of discharge from the vaginal opening and redness and congestion of the vaginal mucosa were recorded, A vaginal health score was performed on a scale of 1 to 4, with higher scores associated with less atrophy, discharge, epithelial mucosa, and wetness. Subjects were rated on this score before and after administration of the scaffold device.

[0107] After 4 weeks of administration, all Subjects showed reduced mucosa thickness, redness, and swelling, decreased discharge, and improved inflammatory conditions, along with higher vaginal health scores. Scaffold degradation was gradual throughout administration, and the scaffold structure disintegrated inside the vagina of subjects after approximately 4-5 days of administration.

[0108] Thus, in some aspects of the present disclosure, a method of testing the friability of a scaffold structure by measuring and comparing is disclosed. The method measures and compares the fabricated weight of the structure and the weight of the structure following simulated handling, packaging, and transportation. In some embodiments, the method further includes forming the device by combining DNase I with chitosan HC1, collagen type I, and carboxymethyl cellulose cross-linking agents, refrigerating and molding the combination to facilitate a suitable structure, and sterilizing the resulting structure to prevent contamination. In some embodiments, the resulting pore diameters range between 0.5 and 3.00cm. In some embodiments, the weight loss of the structure ranges from 0.4% to 1% of total weight during transport conditions. In some embodiments, there is no measured initial burst of delivery for active ingredients and other compounds following insertion into the vaginal cavity of a mammal. In some embodiments, 90% of the drug release of active ingredients ranges from 37.32 hours to 53.12 hours, and successful release to local tissue persists for up to 60 hours. In some embodiments, animal models for safety and efficacy produce a significantly improved vaginal health score after treatment.

[0109] This disclosure is susceptible to modifications and alternative constructions that are fully equivalent to those discussed above. Consequently, this invention is not limited to the particular embodiments disclosed. On the contrary, this invention covers all modifications and alternate constructions coming within the spirit and scope of the invention as generally expressed by the following claims, which particularly point out and distinctly claim the subject matter of the invention. While the disclosure has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive.

[0110] All references cited herein are incorporated herein by reference in their entirety. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.

[0111] Unless otherwise defined, all terms (including technical and scientific terms) are to be given their ordinary and customary meaning to a person of ordinary skill in the art, and are not to be limited to a special or customized meaning unless expressly so defined herein. It should be noted that the use of particular terminology when describing certain features or aspects of the disclosure should not be taken to imply that the terminology is being redefined herein to be restricted to include any specific characteristics of the features or aspects of the disclosure with which that terminology is associated. Terms and phrases used in this application, and variations thereof, especially in the appended claims, unless otherwise expressly stated, should be construed as open-ended as opposed to limiting. As examples of the foregoing, the term ‘including’ should be read to mean ‘including, without limitation,’ ‘including but not limited to,’ or the like; the term ‘comprising’ as used herein is synonymous with ‘including,’ ‘containing,’ or ‘characterized by,’ and is inclusive or open-ended and doesnot exclude additional, unrecited elements or method steps; the term ‘having’ should be interpreted as ‘having at least;’ the term ‘includes’ should be interpreted as ‘includes but is not limited to;’ the term ‘example’ is used to provide exemplary instances of the item in discussion, not an exhaustive or limiting list thereof; adjectives such as ‘known’, ‘normal’, ‘standard’, and terms of similar meaning should not be construed as limiting the item described to a given time period or to an item available as of a given time, but instead should be read to encompass known, normal, or standard technologies that may be available or known now or at any time in the future; and use of terms like ‘preferably,’ ‘preferred,’ ‘desired,’ or ‘desirable,’ and words of similar meaning should not be understood as implying that certain features are critical, essential, or even important to the structure or function of the invention, but instead as merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the invention. Likewise, a group of items linked with the conjunction ‘and’ should not be read as requiring that each and every one of those items be present in the grouping, but rather should be read as ‘and / or’ unless expressly stated otherwise. Similarly, a group of items linked with the conjunction ‘or’ should not be read as requiring mutual exclusivity among that group, but rather should be read as ‘and / or’ unless expressly stated otherwise.

[0112] Where a range of values is provided, it is understood that the upper and lower limit, and each intervening value between the upper and lower limits of the range is encompassed within the embodiments.

[0113] With respect to the use of substantially any plural and / or singular terms herein, those having skill in the art can translate from the plural to the singular and / or from the singular to the plural as is appropriate to the context and / or application. The various singular / plural permutations may be expressly set forth herein for the sake of clarity. The indefinite article ‘a or ‘an does not exclude a plurality. A single processor or other unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

[0114] It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in theclaim, and in the absence of such recitation, no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases at least one’ and “one or more’ to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles ‘a’ or ‘an’ limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases ‘one or more’ or ‘at least one’ and indefinite articles such as ‘a’ or ‘an’ (e.g., ‘a’ and / or ‘an’ should typically be interpreted to mean ‘at least one’ or ‘one or more’); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of ‘two recitations,’ without other modifiers, typically means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to ‘at least one of A, B, and C, etc.’ is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., ‘a system having at least one of A, B, and C’ would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). In those instances where a convention analogous to ‘at least one of A, B, or C, etc.’ is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., ‘a system having at least one of A, B, or C’ would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and / or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and / or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase ‘A or B’ will be understood to include the possibilities of ‘A’ or ‘B’ or ‘A and B.’

[0115] All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification are to be understood as being modified in all instances by the term ‘about.’ Accordingly, unless indicated to the contrary, the numerical parameters set forth herein are approximations that may vary depending upon the desired properties sought to beobtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of any claims in any application claiming priority to the present application, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.

[0116] Furthermore, although the foregoing has been described in some detail by way of illustrations and examples for purposes of clarity and understanding, it is apparent to those skilled in the art that certain changes and modifications may be practiced. Therefore, the description and examples should not be construed as limiting the scope of the invention to the specific embodiments and examples described herein, but rather to also cover all modification and alternatives coming with the true scope and spirit of the invention.

Claims

WHAT IS CLAIMED IS:

1. A porous scaffold device for use in administering a therapeutic compound or composition to a mammal, the device comprising:chitosan;collagen;carboxymethyl cellulose; andan enzyme.

2. The device of claim 1, wherein the therapeutic compound or composition is administered to the mammal by the device being inserted into the vaginal cavity of the mammal.

3. The device of claim 1 or 2, wherein the device is formed in a cylindrical shape, 4. The device of claim 3, wherein the cylindrical shape has a length in a first direction of approximately 0,5 cm to approximately 10 cm, and a diameter of approximately 0.5 cm to approximately 3 cm.

5. The device of any one of claims 1-4, wherein a ratio of chitosan to collagen to carboxymethyl cellulose is about 40:30:30, about 50:25:25, or about 60:20:20 by weight.

6. The device of any one of claims 1-5, wherein the enzyme comprises a DNase and / or a mucolytic enzyme.

7. The device of claim 6, wherein the DNase comprises DNase I.

8. The device of any one of claims 1-7, wherein the chitosan comprises chitosan HC1.

9. The device of any one of claims 1-8, wherein the collagen comprises collagen type I.

10. The device of any one of claims 1-9, wherein the enzyme is included at a concentration of about 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 pg / ml, or any concentration that is between about 10 and about 100 pg / ml.

11. The device of any one of claims 1-10, wherein the device further comprises a pharmaceutically acceptable excipient and the therapeutic compound or composition.

12. The device of any one of claims 1-11, wherein the device is a suppository.

13. The device of any one of claims 1-12, wherein the device allows for the therapeutic compound or composition to be delivered past the vaginal mucus of the mammal.

14. The device of any one of claims 1-13, wherein the mammal is human.

15. The device of any one of claims 1-14, wherein the therapeutic compound or composition comprises a biological material and / or a chemical compound.

16. The device of claim 15, wherein the biological material comprises at least 1, 2, 3, 4 or 5 of: an RNA, DNA, extracellular vesicle, cell, or any combination thereof.

17. The device of claim 15 or 16, wherein the chemical compound comprises at least 1, 2, 3, 4, 5, 6, or 7 of: a small molecule, peptide, protein, antibody, ADS, lipid, lipid-derived molecule, or any combination thereof.

18. A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject the device of any one of claims 1-17, wherein the device further comprises an at least one compound or composition that is therapeutically effective in treating the disease or disorder.

19. The method of claim 18, wherein the device further comprises a pharmaceutically acceptable excipient.

20. The method of claim 18 or 19, wherein the method comprises inserting the device into the vagina of the subject.

21. The method of any one of claims 18-20, wherein the disease or disorder comprises at least one of: vaginal atrophy, vaginal irritation, vaginal burning, urinary tract infection, vaginal infection, frequent urination, or any combination thereof.

22. The method of any one of claims 18-21, wherein the disease or disorder is vaginitis, vulvar cancer, vaginal cancer, or cervical cancer.

23. A method of manufacturing a porous scaffold device for use in administering a therapeutic compound or composition to a mammal, the method comprising:providing chitosan, collagen, carboxymethyl cellulose, and an enzyme to create a mixture;stirring the mixture to form a consistent liquid texture;pouring the liquid into a mold;freezing the liquid to form a porous scaffold device;lyophilizing the scaffold device; andsterilizing the scaffold device.

Images