Microsphere-based injectable finasteride formulation

Abstract

This invention provides a plurality of biodegradable microspheres, wherein the microspheres (i) have a d10 value of at least 1 μm and a d90 value of 28 μm or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month. This invention also provides related injectable formulations, methods for treating hair loss, and articles of manufacture.

Description

[0001] Dk. Avidence-6PCT MICROSPHERE-BASED INJECTABLE FINASTERIDE FORMULATION This application claims the benefit of U.S. Provisional Application No.63 / 639,751, filed April 29, 2024, the contents of which are incorporated herein by reference. Throughout this application, various publications are cited. The disclosure of these publications is hereby incorporated by reference into this application to describe more fully the state of the art to which this invention pertains. Field of the Invention The present invention relates to methods for treating hair loss via localized injection of finasteride-containing biodegradable microspheres. of the Invention Alopecia Hair loss, also known as alopecia, is a common condition that affects both men and women. The most common types of hair loss, such as male-pattern baldness and female-pattern baldness, are associated with altered androgen levels and altered sensitivity to androgens in the hair follicles. Thus, they are known as androgenicalopecia or androgenetic alopecia. In the hair follicle, the enzyme 5 -reductase isresponsible for the production of dihydrotestosterone (DHT) from circulating testosterone in the blood, and DHT around the hair follicle is one major contributor to hair loss. Finasteride -reductase inhibitors such as finasteride and dutasteride have been developed to reduce DHT levels systemically, and in and around the hair follicles in the scalp. However, finasteride is FDA-approved to treat hair loss only via oral administration as atablet. Oral administration of finasteride causes systemic inhibition of 5 -reductase andreduction in DHT levels in many other organs in addition to hair follicles. This causes severe side effects including mood disturbance, gynecomastia, decreased libido, erectile dysfunction, and ejaculation disorder (see, e.g., the FDA label for Propecia®). Topical delivery of finasteride can reduce its systemic exposure and side effects. However, topical delivery carries the additional risk of transference through which finasteride is unintentionally transferred from one person with topically applied finasteride to another person via direct contact or contact with a common surface, such as clothing, a pillow, bedding sheets, or furniture. Given the high potency of finasteride, this transference may cause severe side effects in pregnant women and the fetus (sexual malformation), and in children and adolescents (dysregulated sexual development). These side effects are addressed via localized delivery of finasteride through an injection into the skin or the scalp to act on the hair follicles directly. Thismaximizes local inhibition of 5 -reductase, minimizes systemic side effects, and avoidsthe risk of transference. Ideally, a finasteride formulation should be long-acting and should be locally delivered using a thin needle. These features reduce pain and injection frequency. PLGA Microspheres Generally An important biodegradable material commonly used for extended-release drug delivery is polylactic co-glycolic acid copolymer (PLGA). PLGA is made of polylactic acid (PLA) units, polyglycolic acid (PGA) units, and typically both. As an FDA-approved polymer, it has been extensively investigated in many medical and pharmaceutical fields due to its biodegradability and biocompatibility. PLGA-containing microspheres have shown sustained release characteristics due to degradation and diffusion mechanisms. The drug release profile of a PLGA microsphere preparation is dependent on certain factors, such as the specific properties of the drug, the ratio of PLA to PGA, the type of end cap of the polymer (i.e., ester or acid), the molecular weight and inherent viscosity of the polymer, the loading ratio of drug to the polymer, and the size of the microspheres. Finasteride Microspheres Various PLGA-based microsphere formulations of finasteride are known. In Kim, et al. (2019), the finasteride microspheres have diameter of between 30 µm and 50 µm and finasteride loading ratio of about 20%. In Kim, et al. (2021), the finasteride microspheres have mean diameter of 41-44 µm for the PLGA formulations. In Kang, et al. (2021), the finasteride microspheres have mean diameter of about 40 µm. In Moon, et al., the finasteride microspheres have mean diameter of about 30 µm and show sustained release over 3-4 months. Due to the relatively large size of these known finasteride microspheres, they must be injected with a thick needle, which causes unacceptable pain to highly sensitive facial skin and scalp, especially when multiple injections are needed to treat a large area of hair loss. Thus, these formulations are unsuitable for local injections to facial skin and scalp for the treatment of hair loss. Known Challenges As discussed by Bauer, et al. (2023), microsphere size is important for syringeability (i.e., the "ability to be transferred from a vial through a conventional needle into a syringe") and injectability (i.e., the ability of "transferring of contents [from] the syringe into the body"). Specifically, "[s]yringeability … and injectability … are [the] two most important quality attributes in [the] patient convenience related category. These two quality attributes play a significant part in the LAI [long-acting injectable] administration efficiency. Ideally, the product should be such that injection can be done through smaller needle size of conventional needles, reducing the local tissue damage and associated pain, and enhancing patient compliance. A high level of control over the particle size, shape, density, viscosity, and suspension concentration is required as large particles or aggregates in the formulation often cause needle clogging." (pages 1610 and 1611; citations omitted) Park, et al. (2019) describes how small microspheres are challenging to develop. Specifically, "[t]he important properties of microparticles for clinical applications (or microparticle properties) include a microparticle size small enough for injection, high drug loading, high drug loading efficiency, and long duration of drug release without the huge initial burst release ... One of the important properties to control is the microparticle size. The PLGA microparticle formulation currently in clinical use have large sizes, requiring large-diameter gauge needles for injection. For example, Trelstar and Risperidal Consta ... use 21-gauge needles. … Nutropin Depot … also used the 21-gauge needle. The size of Risperidal Consta microparticles ranges from 25 µm to 180 µm. … Delivery of the extended-release injectable formulation of naltrexone (marketed as Vivitrol) uses a 20-gauge needle. … In comparison, delivery of an insulin typically uses a 28-gauge needle. PLGA microparticles that can be administered using a 28-gauge needle or thinner needles will undoubtedly make clinical use more patient- friendly, although making smaller PLGA microparticles may come at the expense of other properties in Table 2 [drug loading, drug loading efficiency, initial burst release, drug release kinetics]." (pages 128 and 129; emphasis added; citations omitted) For large diameter particles, the small surface area per unit volume leads to reduced rate of water permeation and matrix degradation relative to smaller particles and so the maximum possible rate of encapsulated drug release is reduced. For drugs microencapsulated in larger microparticles, duration of action is potentially longer due to higher total drug loading and a longer particle degradation time. Simply put, small microspheres have higher surface area to volume ratios, which correlates to faster drug release and shorter drug release durations. See, e.g., Han, et al. (2016). Makadia and Siegel (2011) states that “[t]he ratio of surface area to volume has shown to be a significant factor for degradation of large devices [e.g., microspheres]. Higher surface area ratio leads to high degradation of the matrix. It has also been reported that bulk degradation is faster than pure surface degradation for PLGA, which makes the release of the drug faster from the devices with higher surface area to volume." (page 9; citations omitted) Berchane, et al. (2007) provides an example of this problem. Figure 4 of Berchane, et al. shows the release curves of piroxicam poly(lactide-co-glycolide) microspheres of different sizes. The 300-rpm group (mean diameter 33.5 µm from Table 1) has a duration over 30 days, whereas the 900-rpm group (mean diameter 13.5 µm from Table 1) released over 80% of drug in about 12 days. There remains a need for an injectable formulation of finasteride microspheres that are long-lasting and that solve the problems of syringeability and injectability. Summary of the Invention This invention provides a plurality of biodegradable microspheres, wherein the microspheres (i) have a d10 value of at least 1 m and a d90 value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month. This invention also provides an injectable formulation comprising (a) a pharmaceutically acceptable carrier and (b) a plurality of biodegradable microspheres wherein the microspheres (i) have a d10 value of at least 1 m and a d90 value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month. This invention further provides a method for treating hair loss in a subject comprising introducing biodegradable microspheres into an affected area of the subject’s skin, wherein the introducing is into skin at or around one or more hair follicles, and wherein the microspheres (i) have a d10value of at least 1 m and a d90value of 28 µm or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month. This invention further provides an article of manufacture (kit) comprising, in separate compartments, (a) one of, and ideally both of, (i) a diluent and (ii) a label instructing the user to introduce the biodegradable microspheres (described below) into the skin, scalp, or subcutaneous tissue of a subject, and (b) a plurality of biodegradable microspheres, wherein the microspheres (i) have a d10value of at least 1 m and a d90value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month. This invention still further provides an article of manufacture comprising a syringe having therein the instant injectable formulation. Finally, this invention provides an article of manufacture comprising a dual chamber syringe having therein, in separate compartments, (a) a diluent, and (b) plurality of biodegradable microspheres, wherein the microspheres (i) have a d10value of at least 1 m and a d90 value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month, wherein the diluent and microspheres can be admixed within the syringe to form an injectable formulation immediately prior to use.

[0002] Brief Description of the Figures Figure 1 This figure shows dutasteride release from microspheres made with a stir bar. All microspheres showed gaps in drug release. Figure 2 This figure shows a mixer (Model L5MA, Silverson, Massachusetts, US) with an in-line mixing chamber and general-purpose disintegrating head that was used to continuously create oil-in-water emulsions and generate microspheres. Figure 3 This figure shows dutasteride release from microspheres made in a mixing chamber. All groups showed slow dutasteride release after 30 days. Figures 4A-4D These figures show dutasteride release from microspheres of different PLGA types. Incomplete drug release was observed in all groups except the 5 mg dutasteride group. Figure 5 This figure shows finasteride release from short-acting microspheres with release duration less than one month. Figure 6 This figure shows finasteride release from long-acting microspheres with release duration over at least one month. Figures 7A-7C These figures show the effect of increasing finasteride:PLGA ratio on drug release. Figure 7C shows strong burst release associated with an excessively high finasteride:PLGA ratio. In Figures 7A and 7B, a significant gap in finasteride release was observed in the PLGA75:25, 0.4 dl / g, acid-terminated:PLGA75:25, 0.6 dl / g, ester- terminated=25:75 group. Figures 8A and 8B These figures show continuous finasteride release from microspheres prepared in a mixing chamber over at least two months. Figures 9A and 9B These figures show continuous finasteride release from microspheres of different sizes. Reducing particle size did not affect the total duration of finasteride release. Figures 10A and 10B These figures show continuous finasteride release from microspheres after 15 kGy E- beam irradiation over one to four months. Figure 11 This figure shows continuous finasteride release from microspheres over at least three to six months in vitro. Figures 12A-12E These figures show continuous finasteride release from microspheres over six months in vitro. Figure 12A - irradiated microspheres (17-1, 17-2, 17-3, and 17-4); Figure 12B - un-irradiated microspheres (17-1, 17-2, 17-3, and 17-4); Figure 12C - un-irradiated microspheres (17-5, 17-6, 17-7, and 17-8); Figure 12D - un-irradiated microspheres (17- 9, 17-10, 17-11, and 17-12); and Figure 12E - un-irradiated microspheres (17-13, 17-14, 17-15, and 17-16). Detailed Description of the Invention This invention provides finasteride-containing biodegradable microspheres and methods for using them to treat hair loss. Definitions In this application, certain terms are used which shall have the meanings set forth as follows. As used herein, a “biodegradable microsphere” comprises a polylactic-co-glycolic acid copolymer (PLGA) matrix, which matrix can include solely polylactic acid (PLA), solely polyglycolic acid (PGA), or a polymeric combination of lactic acid and glycolic acid units. In general, for certain lactic acid to glycolic acid ratios (e.g., 50:50 to 100:0), the higher a microsphere’s lactic acid content, the slower it degrades and, thus, the more stable it is. Conversely, for such ratios, the higher a microsphere’s glycolic acid content, the faster it degrades and the less stable it is. In one embodiment, the biodegradable microsphere contains a combination of lactic acid and glycolic acid units wherein the molar ratio of lactic acid to glycolic acid units (i.e., the “lactic acid to glycolic acid ratio”, or “L:G ratio”) is 0:100, 5:95, 10:90, 15:85, 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 71:29, 72:28, 73:27, 74:26, 75:25, 76:24, 77:23, 78:22, 79:21, 80:20, 81:19, 82:18, 83:17, 84:16, 85:15, 86:14, 87:13, 88:12, 89:11, 90:10, 95:5, or 100:0. In another embodiment, the biodegradable microsphere contains a combination of lactic acid and glycolic acid units wherein the molar ratio of lactic acid to glycolic acid is from 5:95 to 20:80, from 20:80 to 40:60, from 40:60 to 50:50, from 50:50 to 60:40, from 60:40 to 80:20, from 70:30 to 90:10, from 80:20 to 100:0, from 50:50 to 100:0, from 60:40 to 90:10, from 70:30 to 80:20, from 71:29 to 76:24, from 72:28 to 77:23, from 73:27 to 78:22, from 74:26 to 79:21, from 71:29 to 79:21, from 72:28 to 78:22, from 73:27 to 77:23, from 74:26 to 76:24, from 50:50 to 80:20, from 50:50 to 90:10, from 60:40 to 70:30, from 80:20 to 90:10, from 81:19 to 86:14, from 82:18 to 87:13, from 83:17 to 88:12, from 84:16 to 89:11, from 81:19 to 89:11, from 82:18 to 88:12, from 83:17 to 87:13, from 84:16 to 86:14, or from 90:10 to 100:00. The population of biodegradable microspheres used in this invention can be homogeneous or heterogeneous with respect to the microspheres’ molar ratio of lactic acid to glycolic acid. In one embodiment, the population of biodegradable microspheres is homogeneous with respect to the microspheres’ molar ratio of lactic acid to glycolic acid (e.g., the population includes only microspheres wherein the molar ratio of lactic acid to glycolic acid is 75:25 or 85:15). In another embodiment, the population of biodegradable microspheres is heterogeneous (e.g., the population includes both (i) microspheres wherein the molar ratio of lactic acid to glycolic acid is 70:30, and (ii) microspheres wherein the molar ratio of lactic acid to glycolic acid is 80:20). In a preferred embodiment, the instant microspheres contain PLGA having an inherent viscosity of 0.1 to 2.4 dl / g (e.g., 0.16 to 1.7 dl / g), and a molecular weight from 1,000 to 600,000 (e.g., from 7,000 to 240,000). In one embodiment, the biodegradable microsphere has an inherent viscosity of 0.1 dl / g, 0.2 dl / g, 0.3 dl / g, 0.4 dl / g, 0.5 dl / g, 0.6 dl / g, 0.7 dl / g, 0.8 dl / g, 0.9 dl / g, 1.0 dl / g, 1.1 dl / g, 1.2 dl / g, 1.3 dl / g, 1.4 dl / g, 1.5 dl / g, 1.6 dl / g, 1.7 dl / g, 1.8 dl / g, 1.9 dl / g, 2.0 dl / g, 2.1 dl / g, 2.2 dl / g, 2.3 dl / g, or 2.4 dl / g. In another embodiment, the biodegradable microsphere has an inherent viscosity of from 0.1 dl / g to 0.2 dl / g, from 0.2 dl / g to 0.3 dl / g, from 0.3 dl / g to 0.4 dl / g, from 0.4 dl / g to 0.5 dl / g, from 0.5 dl / g to 0.6 dl / g, from 0.6 dl / g to 0.7 dl / g, from 0.7 dl / g to 0.8 dl / g, from 0.8 dl / g to 0.9 dl / g, from 0.9 dl / g to 1.0 dl / g, from 1.0 dl / g to 1.1 dl / g, from 1.1 dl / g to 1.2 dl / g, from 1.2 dl / g to 1.3 dl / g, from 1.3 dl / g to 1.4 dl / g, from 1.4 dl / g to 1.5 dl / g, from 1.5 dl / g to 1.6 dl / g, from 1.6 dl / g to 1.7 dl / g, from 1.7 dl / g to 1.8 dl / g, from 1.8 dl / g to 1.9 dl / g, from 1.9 dl / g to 2.0 dl / g, from 2.0 dl / g to 2.1 dl / g, from 2.1 dl / g to 2.2 dl / g, from 2.2 dl / g to 2.3 dl / g, or from 2.3 dl / g to 2.4 dl / g. In a further embodiment, the biodegradable microsphere has an inherent viscosity of from 0.1 dl / g to 0.5 dl / g, from 0.5 dl / g to 1.0 dl / g, from 1.0 dl / g to 1.5 dl / g, from 1.5 dl / g to 2.0 dl / g, from 2.0 dl / g to 2.4 dl / g, from 0.3 dl / g to 1.3 dl / g, or from 1.3 dl / g to 1.7 dl / g. Preferred embodiments of the present microspheres are PLGA75:25, 0.3-1.3 dl / g and PLGA85:15, 1.3-1.7 dl / g, having a d10 value of at least 3 m and a d90value of 25 m or less. In a further embodiment, the drug loading ratio for the present biodegradable microsphere is from 20% to 25%, from 25% to 30%, from 30% to 35%, from 30.1% to 34.9%, from 30.5% to 34.5%, from 31% to 34%, from 35% to 40%, from 40% to 45%, from 45% to 50%, from 50% to 55%, from 55% to 60%, from 60% to 65%, from 65% to 70%, from 20% to 30%, from 25% to 35%, from 30% to 40%, from 35% to 45%, from 40% to 50%, from 45% to 55%, from 50% to 60%, from 55% to 65%, from 60% to 70%, from 65% to 75%, from 20% to 35%, from 20% to 40%, from 30% to 50%, from 40% to 60%, from 50% to 70%, from 20% to 50%, from 30% to 60%, or from 40% to 70%. In the present plurality of biodegradable microspheres, the microspheres (i) have a d10value of at least 1 m and a d90 value of 28 m or less; (ii) non-covalently carry a therapeutic agent (finasteride); and (iii) depending on their polymeric composition, degrade over a period lasting, for example, from one month to over six months when present intradermally. Microsphere diameter ranges, set forth as ranges from d10 to d90 (as defined herein), include, for example, the following: (i) from 1 m to 10 m, from 1 m to 15 m, from 1 m to 20 m, from 1 m to 25 m, from 1 m to 28 m, from 5 m to 10 m, from 5 m to 15 m, from 5 m to 20 m, from 5 m to 25 m, from 5 m to 28 m, from 10 m to 15 m, from 10 m to 20 m, from 10 m to 25 m, from 10 m to 28 m, from 15 m to 20 m, from 15 m to 25 m, and from 15 m to 28 m; (ii) from 2 m to 28 m, from 3 m to 28 m, from 4 m to 28 m, from 6 m to 28 m, from 7 m to 28 m, from 8 m to 28 m, and from 9 m to 28 m; (iii) from 1 m to 27 m, from 2 m to 27 m, from 3 m to 27 m, from 4 m to 27 m, from 5 m to 27 m, from 6 m to 27 m, from 7 m to 27 m, from 8 m to 27 m, and from 9 m to 27 m; (iv) from 1 m to 26 m, from 2 m to 26 m, from 3 m to 26 m, from 4 m to 26 m, from 5 m to 26 m, from 6 m to 26 m, from 7 m to 26 m, from 8 m to 26 m, and from 9 m to 26 m; (v) from 2 m to 25 m, from 3 m to 25 m, from 4 m to 25 m, from 5 m to 25 m, from 6 m to 25 m, from 7 m to 25 m, from 8 m to 25 m, and from 9 m to 25 m; (vi) from 1 m to 24 m, from 2 m to 24 m, from 3 m to 24 m, from 4 m to 24 m, from 5 m to 24 m, from 6 m to 24 m, from 7 m to 24 m, from 8 m to 24 m, and from 9 m to 24 m; (vii) from 1 m to 23 m, from 2 m to 23 m, from 3 m to 23 m, from 4 m to 23 m, from 5 m to 23 m, from 6 m to 23 m, from 7 m to 23 m, from 8 m to 23 m, and from 9 m to 23 m; (viii) from 1 m to 22 m, from 2 m to 22 m, from 3 m to 22 m, from 4 m to 22 m, from 5 m to 22 m, from 6 m to 22 m, from 7 m to 22 m, from 8 m to 22 m, and from 9 m to 22 m; (ix) from 1 m to 21 m, from 2 m to 21 m, from 3 m to 21 m, from 4 m to 21 m, from 5 m to 21 m, from 6 m to 21 m, from 7 m to 21 m, from 8 m to 21 m, and from 9 m to 21 m; and (x) from 1 m to 20 m, from 2 m to 20 m, from 3 m to 20 m, from 4 m to 20 m, from 5 m to 20 m, from 6 m to 20 m, from 7 m to 20 m, from 8 m to 20 m, and from 9 m to 20 m. In a further embodiment, the d10values for the present microsphere diameters include the following: (i) 1.0 m, 1.5 m, 2.0 m, 2.5 m, 3.0 m, 3.5 m, 4.0 m, 4.5 m, 5.0 m, 5.5 m, 6.0 m, 6.5 m, 7.0 m, 7.5 m, 8.0 m, 8.5 m, 9.0 m, 9.5 m, 10.0 m, m, 11.0 m, 11.5 m, 12.0 m, 12.5 m, 13.0 m, 13.5 m, 14.0 m, 14.5 m, and 15.0 m; (ii) from 1.0 m to 2.0 m, from 2.0 m to 3.0 m, from 3.0 m to 4.0 m, from 4.0 m to 5.0 m, from 5.0 m to 6.0 m, from 6.0 m to 7.0 m, from 7.0 m to m, from 8.0 m to 9.0 m, from 9.0 m to 10.0 m, from 10.0 m to 11.0 m, from m to 12.0 m, from 12.0 m to 13.0 m, from 13.0 m to 14.0 m, and from 14.0 m to 15.0 m; (iii) from 1.0 m to 3.0 m, from 3.0 m to 5.0 m, from 5.0 m to 7.0 m, from 7.0 m to 9.0 m, from 9.0 m to 11.0 m, from 11.0 m to 13.0 m, and from m to 15.0 m; and (iv) from 1.0 m to 5.0 m, from 5.0 m to 10.0 m, and from m to 15.0 m. In a further embodiment, the d50values for the present microsphere diameters include the following: (i) 5.0 m, 5.5 m, 6.0 m, 6.5 m, 7.0 m, 7.5 m, 8.0 m, 8.5 m, 9.0 m, 9.5 m, 10.0 m, 10.5 m, 11.0 m, 11.5 m, 12.0 m, 12.5 m, 13.0 m, 13.5 m, m, 14.5 m, 15.0 m, 15.5 m, 16.0 m, 16.5 m, 17.0 m, 17.5 m, 18.0 m, m, 19.0 m, 19.5 m, and 20.0 m; (ii) from 5.0 m to 6.0 m, from 6.0 m to 7.0 m, from 7.0 m to 8.0 m, from 8.0 m to 9.0 m, from 9.0 m to 10.0 m, from 10.0 m to 11.0 m, from 11.0 m to 12.0 m, from 12.0 m to 13.0 m, from 13.0 m to m, from 14.0 m to 15.0 m, from 15.0 m to 16.0 m, from 16.0 m to 17.0 m, from 17.0 m to 18.0 m, from 18.0 m to 19.0 m, and from 19.0 m to 20.0 m; (iii) from 5.0 m to 7.0 m, from 7.0 m to 9.0 m, from 9.0 m to 11.0 m, from 11.0 m to m, from 13.0 m to 15.0 m, from 15.0 m to 17.0 m, from 17.0 m to 19.0 m, and from 19.0 m to 20.0 m; and (iv) from 5.0 m to 10.0 m, from 10.0 m to 15.0 m, and from 15.0 m to 20.0 m. In a further embodiment, the d90 values for the present microsphere diameters include the following: (i) 10.0 m, 10.5 m, 11.0 m, 11.5 m, 12.0 m, 12.5 m, 13.0 m, 13.5 m, 14.0 m, 14.5 m, 15.0 m, 15.5 m, 16.0 m, 16.5 m, 17.0 m, 17.5 m, 18.0 m, 18.5 m, 19.0 m, 19.5 m, 20.0 m, 20.5 m, 21.0 m, 21.5 m, 22.0 m, 22.5 m, 23.0 m, 23.5 m, 24.0 m, 24.5 m, 25.0 m, 25.5 m, 26.0 m, 26.5 m, 27.0 m, 27.5 m, and 28.0 m; (ii) from 10.0 m to 11.0 m, from 11.0 m to 12.0 m, from m to 13.0 m, from 13.0 m to 14.0 m, from 14.0 m to 15.0 m, from 15.0 m to 16.0 m, from 16.0 m to 17.0 m, from 17.0 m to 18.0 m, from 18.0 m to 19.0 m, from 19.0 m to 20.0 m, from 20.0 m to 21.0 m, from 21.0 m to 22.0 m, from m to 23.0 m, from 23.0 m to 24.0 m, from 24.0 m to 25.0 m, from 25.0 m to 26.0 m, from 26.0 m to 27.0 m, and from 27.0 m to 28.0 m; (iii) from 10.0 m to12 m, from 12.0 m to 14.0 m, from 14.0 m to 16.0 m, from 16.0 m to 18.0 m,from 18.0 m to 20.0 m, from 20.0 m to 22.0 m, from 22.0 m to 24.0 m, from 24.0 m to 26.0 m, and from 26.0 m to 28.0 m; and (iv) from 10.0 m to 15.0 m, from m to 20.0 m, from 20.0 m to 25.0 m, and from 25.0 m to 28.0 m. The subject biodegradable microspheres can further comprise polyethylene glycol (PEG). Biodegradable PLGA microspheres (including homogeneous and heterogeneous populations thereof having defined molar ratios of lactic acid to glycolic acid units) are commercially available from, among other sources, Millipore-Sigma in the form of Degradex®products (Burlington, MA) and Evonik Industries in the form of Resomer®products (Essen, Germany). As used herein, the term “carry”, with respect to pharmaceutical finasteride and a biodegradable microsphere, means that the pharmaceutical finasteride is non-covalently bound to, or otherwise contained in or on, the biodegradable microsphere in a manner permitting release from the microsphere during its biodegradation. As used herein, the term “diluent” includes, without limitation, sodium chloride, carboxymethylcellulose sodium, polysorbate 80, mannitol (which can optionally be incorporated on and / or into the microspheres to improve suspendability), water, and medium-chain fatty acids. As used herein, the term “d90 value”, with respect to the present microspheres, means the 90thpercentile diameter in the microsphere population on a volume-weighted basis. The term “d50value” means the 50thpercentile diameter in the microsphere population on a volume-weighted basis. The term “d10 value” means the 10thpercentile diameter in the microsphere population on a volume-weighted basis.As used herein, the term “finasteride” is also known as, for example, (5 -N-(1,1-dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide, N-tert-Butyl-3-oxo-4-aza-5 -androst-1-ene-17 -carboxamide, 17 -(N-tert-Butylcarbamoyl)-4-aza-5 -androst-1-en-3-one, and N-(1,1-Dimethylethyl)-3-oxo-4-aza-5 -androst-1-ene-17 -carboxamide, andhas CAS number 98319-26-7. Finasteride is a specific inhibitor of steroid Type II 5 -reductase, an intracellular enzyme that converts the androgen testosterone into 5 -dihydrotestosterone. It is commercially known and is sold by Merck under the trade name Propecia®and Proscar®. As used herein, “intradermally”, includes, without limitation, (i) situated within one or more layers of the skin or (ii) situated between two or more layers of the skin. These layers of skin include, for example, the epidermis (e.g., the stratum corneum, the stratum lucidum, the stratum granulosum, the stratum spinosum, and / or the stratum basale), the dermis, and the hypodermis. In a preferred embodiment, intradermally means situated in the dermis. In another embodiment, intradermally means situated in the epidermis. In a further embodiment, intradermally means situated in the hypodermis. As used herein, “introducing”, with respect to biodegradable microspheres, means delivering to a specified part of the body, such as skin, scalp, or subcutaneous tissue. Methods of introducing biodegradable microspheres to the subcutaneous tissue are known and include, for example, Lupron Injection. See, e.g., the Lupron®label. Methods of introducing drugs to the scalp are known and include, for example, Botox injection for chronic migraine. See, e.g., the Botox®label. The present biodegradable microspheres can be delivered to the skin, scalp, or subcutaneous tissue through one or multiple injections at a time to cover a larger area under treatment. For example, Botox®Cosmetic is delivered to treat wrinkles through multiple injections. See, e.g., the Botox®Cosmetic label. As used herein, “hair loss” includes, without limitation, androgenic alopecia, male- pattern baldness, female-pattern baldness, drug-induced hair loss (e.g., chemotherapy- induced hair loss), radiotherapy-induced hair loss, alopecia areata, alopecia universalis, traction alopecia, frontal fibrosing alopecia, central centrifugal cicatricial alopecia, anagen effluvium, telogen effluvium, scarring alopecia, tinea capitis, and involutional alopecia. As used herein, the term “pharmaceutical finasteride” includes, without limitation, finasteride and pharmaceutical salts and esters thereof. “Pharmaceutically acceptable carriers” are well known and include, without limitation, the diluents described herein. As used herein, a biodegradable microsphere “releases” finasteride when some or all of the finasteride contained by the microsphere is freed into the microsphere’s surrounding milieu. Preferably, the release is continuous. For example, in a plurality of finasteride- carrying biodegradable microspheres having an average release per day of X mg, the finasteride released per day is, e.g., from 0.1X mg to 10X mg, from 0.2X mg to 10X mg, from 0.3X mg to 10X mg, from 0.4X mg to 10X mg, from 0.5X mg to 10X mg, from 0.1X mg to 9X mg, from 0.2X mg to 9X mg, from 0.3X mg to 9X mg, from 0.4X mg to 9X mg, from 0.5X mg to 9X mg, from 0.1X mg to 8X mg, from 0.2X mg to 8X mg, from 0.3X mg to 8X mg, from 0.4X mg to 8X mg, from 0.5X mg to 8X mg, from 0.1X mg to 7X mg, from 0.2X mg to 7X mg, from 0.3X mg to 7X mg, from 0.4X mg to 7X mg, from 0.5X mg to 7X mg, from 0.1X mg to 6X mg, from 0.2X mg to 6X mg, from 0.3X mg to 6X mg, from 0.4X mg to 6X mg, from 0.5X mg to 6X mg; from 0.1X mg to 5X mg, from 0.2X mg to 5X mg, from 0.3X mg to 5X mg, from 0.4X mg to 5X mg, from 0.5X mg to 5X mg, from 0.1X mg to 4X mg, from 0.2X mg to 4X mg, from 0.3X mg to 4X mg, from 0.4X mg to 4X mg, from 0.5X mg to 4X mg, from 0.1X mg to 3X mg, from 0.2X mg to 3X mg, from 0.3X mg to 3X mg, from 0.4X mg to 3X mg, from 0.5X mg to 3X mg, from 0.1X mg to 2X mg, from 0.2X mg to 2X mg, from 0.3X mg to 2X mg, from 0.4X mg to 2X mg, or from 0.5X mg to 2X mg. In another example, in a plurality of finasteride-carrying biodegradable microspheres having an average release per week of X mg, the finasteride released per week is, e.g., from 0.1X mg to 10X mg, from 0.2X mg to 10X mg, from 0.3X mg to 10X mg, from 0.4X mg to 10X mg, from 0.5X mg to 10X mg, from 0.1X mg to 9X mg, from 0.2X mg to 9X mg, from 0.3X mg to 9X mg, from 0.4X mg to 9X mg, from 0.5X mg to 9X mg, from 0.1X mg to 8X mg, from 0.2X mg to 8X mg, from 0.3X mg to 8X mg, from 0.4X mg to 8X mg, from 0.5X mg to 8X mg, from 0.1X mg to 7X mg, from 0.2X mg to 7X mg, from 0.3X mg to 7X mg, from 0.4X mg to 7X mg, from 0.5X mg to 7X mg, from 0.1X mg to 6X mg, from 0.2X mg to 6X mg, from 0.3X mg to 6X mg, from 0.4X mg to 6X mg, from 0.5X mg to 6X mg; from 0.1X mg to 5X mg, from 0.2X mg to 5X mg, from 0.3X mg to 5X mg, from 0.4X mg to 5X mg, from 0.5X mg to 5X mg, from 0.1X mg to 4X mg, from 0.2X mg to 4X mg, from 0.3X mg to 4X mg, from 0.4X mg to 4X mg, from 0.5X mg to 4X mg, from 0.1X mg to 3X mg, from 0.2X mg to 3X mg, from 0.3X mg to 3X mg, from 0.4X mg to 3X mg, from 0.5X mg to 3X mg, from 0.1X mg to 2X mg, from 0.2X mg to 2X mg, from 0.3X mg to 2X mg, from 0.4X mg to 2X mg, or from 0.5X mg to 2X mg. As used herein, the term “subject” includes, without limitation, a mammal such as a human. As used herein, the term “therapeutically effective amount”, with respect to pharmaceutical finasteride carried in biodegradable microspheres, refers to the amount of pharmaceutical finasteride collectively carried by the total dose of biodegradable microspheres introduced into an affected area of the subject’s skin (e.g., the scalp or subcutaneous tissue). In one embodiment, the effective amount is 1 g, 5 g, 10 g, 15 g, 20 g, 25 g, 30 g, 40 g, 50 g, 60 g, 70 g, 80 g, 90 g, 100 g, 150 g, 200 g, 250 g, 300 g, 350 g, 400 g, 450 g, 500 g, 550 g, 600 g, 650 g, 700 g, 750 g, 800 g, 850 g, 900 g, 950 g, 1mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1,000 mg, 1,050 mg, 1,100 mg, 1,150 mg, 1,200 mg, 1,250 mg, 1,300 mg, 1,350 mg, 1,400 mg, 1,450 mg, 1,500 mg, 1,550 mg, 1,600 mg, 1,650 mg, 1,700 mg, 1,750 mg, 1,800 mg, 1,850 mg, 1,900 mg, 1,950 mg, 2,000 mg, 2,050 mg, 2,100 mg, 2,150 mg, 2,200 mg, 2,250 mg, 2,300 mg, 2,350 mg, 2,400 mg, 2,450 mg, 2,500 mg, 2,550 mg, 2,600 mg, 2,650 mg, 2,700 mg, 2,750 mg, 2,800 mg, 2,850 mg, 2,900 mg, 2,950 mg, or 3,000 mg. In another embodiment, the effective amount is from 1 g to 10 g, from 10 g to 50 g, from 50 g to 100 g, from 100 g to 150 g, from 150 g to 200 g, from 200 g to 250 g, from 250 g to 300 g, from 300 g to 350 g, from 350 g to 400 g, from 400 g to 450 g, from 450 g to 500 g, from 500 g to 550 g, from 550 g to 600 g, from 600 g to 650 g, from 650 g to 700 g, from 700 g to 750 g, from 750 g to 800 g, from 800 g to 850 g, from 850 g to 900 g, from 900 g to 950 g, from 950 g to 1 mg, 1 mg to 10 mg, from 10 mg to 50 mg, from 50 mg to 100 mg, from 100 mg to 150 mg, from 150 mg to 200 mg, from 200 mg to 250 mg, from 250 mg to 300 mg, from 300 mg to 350 mg, from 350 mg to 400 mg, from 400 mg to 450 mg, from 450 mg to 500 mg, from 500 mg to 550 mg, from 550 mg to 600 mg, from 600 mg to 650 mg, from 650 mg to 700 mg, from 700 mg to 750 mg, from 750 mg to 800 mg, from 800 mg to 850 mg, from 850 mg to 900 mg, from 900 mg to 950 mg, from 950 mg to 1,000 mg, from 1,000 mg to 1,050 mg, from 1,050 mg to 1,100 mg, from 1,100 mg to 1,150 mg, from 1,150 mg to 1,200 mg, from 1,200 mg to 1,250 mg, from 1,250 mg to 1,300 mg, from 1,300 mg to 1,350 mg, from 1,350 mg to 1,400 mg, from 1,400 mg to 1,450 mg, from 1,450 mg to 1,500 mg, from 1,500 mg to 1,550 mg, from 1,550 mg to 1,600 mg, from 1,600 mg to 1,650 mg, from 1,650 mg to 1,700 mg, from 1,700 mg to 1,750 mg, from 1,750 mg to 1,800 mg, from 1,800 mg to 1,850 mg, from 1,850 mg to 1,900 mg, from 1,900 mg to 1,950 mg, from 1,950 mg to 2,000 mg, from 2,000 mg to 2,050 mg, from 2,050 mg to 2,100 mg, from 2,100 mg to 2,150 mg, from 2,150 mg to 2,200 mg, from 2,200 mg to 2,250 mg, from 2,250 mg to 2,300 mg, from 2,300 mg to 2,350 mg, from 2,350 mg to 2,400 mg, from 2,400 mg to 2,450 mg, from 2,450 mg to 2,500 mg, from 2,500 mg to 2,550 mg, from 2,550 mg to 2,600 mg, from 2,600 mg to 2,650 mg, from 2,650 mg to 2,700 mg, from 2,700 mg to 2,750 mg, from 2,750 mg to 2,800 mg, from 2,800 mg to 2,850 mg, from 2,850 mg to 2,900 mg, from 2,900 mg to 2,950 mg, or from 2,950 mg to 3,000 mg. In a further embodiment, the effective amount is from 1 g to 250 g, from 250 g to 500 g, from 500 g to 750 g, from 750 g to 1 mg, 1 mg to 250 mg, from 250 mg to 500 mg, from 500 mg to 750 mg, from 750 mg to 1,000 mg, from 1,000 mg to 1,250 mg, from 1,250 mg to 1,500 mg, from 1,500 mg to 1,750 mg, from 1,750 mg to 2,000 mg, from 2,000 mg to 2,250 mg, from 2,250 mg to 2,500 mg, from 2,500 mg to 2,750 mg, or from 2,750 mg to 3,000 mg. In yet a further embodiment, the effective amount is from 1 g to 500 g, from 500 g to 1 mg, from 1 mg to 500 mg, from 10 mg to 500 mg, from 500 mg to 1,000 mg, from 1,000 mg to 1,500 mg, from 1,500 mg to 2,000 mg, from 2,000 mg to 2,500 mg, or from 2,500 mg to 3,000 mg. As used herein, “treating” a subject afflicted with hair loss shall include, without limitation, (i) slowing, stopping, or reversing the progression of hair loss, (ii) reducing the likelihood of the recurrence of hair loss, and / or (iii) preventing the occurrence of hair loss before its onset. In the preferred embodiment, treating a subject afflicted with hair loss means reversing the progression of hair loss, ideally to the point of eliminating the hair loss. Embodiments of the Invention This invention solves an unmet need in the art by providing an unexpectedly superior way to treat hair loss using finasteride. The invention does this via finasteride-carrying microspheres that can be injected to the affected area with an acceptably thin needle and release finasteride over time. Specifically, this invention provides a plurality of biodegradable microspheres, wherein the microspheres (i) have a d10value of at least 1 m and a d90value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month. In an embodiment of the instant plurality of biodegradable microspheres, the microspheres further comprise polyethylene glycol (PEG). The PEG can be any type suitable for use in forming biodegradable microspheres (e.g., PEG1450 (Polysciences, Inc., Warrington, PA)). Moreover, the ratio of PEG to PLGA can be any ratio suitable for use in forming biodegradable microspheres (e.g., 25:100, 50:100, 75:100 or 100:100). In another embodiment of the instant plurality of biodegradable microspheres, the microspheres, when present intradermally (e.g., in the skin, scalp, or subcutaneous tissue), release finasteride for longer than one month. Preferably, the microspheres, when present intradermally, release finasteride for at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months. In a further embodiment of the instant plurality of biodegradable microspheres, the microspheres (i) have a d10 value of at least 3 m and a d90 value of 25 m or less; (ii) have a lactic acid to glycolic acid molar ratio of from 100:0 to 50:50; and (iii) carry from 1 g to 3,000 mg of pharmaceutical finasteride. The following finasteride-containing biodegradable microspheres are preferred embodiments of this invention. The microsphere population comprises PLGA75:25 (i.e., wherein the L:G ratio is 75:25), 0.3-1.3 dl / g, acid-terminated or ester-terminated or mixture from acid- and ester-terminated, with a d10 value of at least 3 m and a d90 value of 25 m or less. The microsphere population may also comprise PLGA85:15 (i.e., wherein the L:G ratio is 85:15), 1.3-1.7 dl / g, ester-terminated, with a d10 value of at least 3 m and a d90 value of 25 m or less. For example, these microsphere populations can be prepared by mixing 12 ml dichloromethane solution containing 600 mg finasteride and 480 mg PLGA (L:G ratio of 75:25 or 85:15, 0.3-1.7 dl / g, acid- terminated or ester-terminated or mixed) and 0.11% polyvinyl alcohol 4-88 in an in-line mixing chamber (model L5MA, Silverson, Massachusetts, US) at the infusion rates of 4 ml / min and 800 ml / min, respectively, and at a mixing speed of 4,400 rpm, followed by solidification on top of 2 L water under stirring at 500 rpm for at least 30 minutes, filtering between a 45 µm sieve and a 5 µm PTFE membrane, and washing with water. For another example, these microsphere populations can be prepared by mixing 40 ml dichloromethane solution containing 1.2 g finasteride and 1.8 of PLGA (L:G ratio of 75:25 or 85:15, 0.3-1.7 dl / g, acid-terminated or ester-terminated or mixed) and 0.11% polyvinyl alcohol 4-88 in an in-line mixing chamber (model L5MA, Silverson, Massachusetts, US) at the infusion rates of 4 ml / min and 800 ml / min, respectively, and at a mixing speed of 4,400 rpm, followed by solidification on top of 8 L water under stirring at 500 rpm for at least 30 minutes, filtering between a 45 µm sieve and a 5 µm PTFE membrane, and washing with water. This invention further provides an injectable formulation comprising (a) a pharmaceutically acceptable carrier and (b) a plurality of biodegradable microspheres wherein the microspheres (i) have a d10value of at least 1 m and a d90value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month. In an embodiment of the instant injectable formulation, the microspheres further comprise polyethylene glycol (PEG). In another embodiment of the instant injectable formulation, the microspheres, when present intradermally, release finasteride for longer than one month. Preferably, the microspheres, when present intradermally, release finasteride for at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months. This invention still further provides a method for treating hair loss in a subject comprising introducing biodegradable microspheres into an affected area of the subject’s skin, wherein the introducing is into skin at or around one or more hair follicles, and wherein the microspheres (i) have a d10 value of at least 1 m and a d90 value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month. In the preferred embodiment, the affected area of the subject’s skin is the subject’s scalp. In another embodiment, the affected area of the subject’s skin is the subject’s face. Skin at or around a hair follicle includes, without limitation, skin within 1 cm of the hair follicle, within 9 mm of the hair follicle, within 8 mm of the hair follicle, within 7 mm of the hair follicle, within 6 mm of the hair follicle, within 5 mm of the hair follicle, within 4 mm of the hair follicle, within 3 mm of the hair follicle, within 2 mm of the hair follicle, within 1 mm of the hair follicle, within 0.9 mm of the hair follicle, within 0.8 mm of the hair follicle, within 0.7 mm of the hair follicle, within 0.6 mm of the hair follicle, within 0.5 mm of the hair follicle, within 0.4 mm of the hair follicle, within 0.3 mm of the hair follicle, within 0.2 mm of the hair follicle, or within 0.1 mm of the hair follicle. In an embodiment of the instant therapeutic method, the microspheres further comprise polyethylene glycol (PEG). In the preferred embodiment of the instant therapeutic method, the subject is human. In another preferred embodiment of the instant therapeutic method, the hair loss is androgenic alopecia (e.g., in men or in women). In another embodiment of the instant therapeutic method, the microspheres (i) have a d10value of at least 3 m and a d90value of 25 m or less; (ii) have a lactic acid to glycolic acid molar ratio of from 100:0 to 50:50; and (iii) carry from 1 g to 3,000 mg of pharmaceutical finasteride. Preferably, the microspheres have an average lactic acid to glycolic acid molar ratio of 75:25 or 85:15. In another embodiment of the instant therapeutic method, the microspheres, when present intradermally, release finasteride for longer than one month. Preferably, the microspheres, when present intradermally, release finasteride for at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months. In this invention, the biodegradable microspheres can be introduced into the affected area of the subject’s skin (e.g., the subject’s scalp, face, or subcutaneous tissue) using any known method appropriate for the tissue in question. For example, in a preferred embodiment of the instant method where the tissue is the scalp, the method comprises injecting the biodegradable microspheres into the scalp. The microspheres can be introduced via a single injection or, preferably, via multiple injections (e.g., at least 5, at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 150, at least 200, at least 300, at least 400, or at least 500 injections) to cover a larger area under treatment. In another embodiment, the instant method is performed a plurality of times (e.g., two times, three times, four times, five times, or more). In that embodiment, each subsequent time the method is performed, it is performed after a suitable period has lapsed since the preceding time the method was performed. This suitable time can be, for example, one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, one year, or longer. Microsphere-based drug products and methods of delivering them are known, at least generally (e.g., Lupron®(leuprolide acetate microspheres for depot suspension (Abbvie)); and Sandostatin LAR®Depot (octreotide acetate for injectable suspension) (Novartis)). This invention also provides an article of manufacture (kit) comprising, in separate compartments, (a) one of, and ideally both of, (i) a diluent and (ii) a label instructing the user to introduce the biodegradable microspheres (described below) into the affected area of a subject’s skin (e.g., the subject’s scalp, face, or subcutaneous tissue), and (b) plurality of biodegradable microspheres, wherein the microspheres (i) have a d10 value of at least 1 m and a d90 value of 28 m or less (e.g., a d10 value of least 3 m and a d90value of 25 m or less); (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix (preferably having a lactic acid to glycolic acid molar ratio of from 100:0 to 50:50 (e.g., 75:25 or 85:15)); (iii) carry a therapeutically effective amount of pharmaceutical finasteride (e.g., from 1 g to 3,000 mg of pharmaceutical finasteride); and (iv) when present intradermally, release finasteride for at least one month (and optionally release finasteride for at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months). In one embodiment of the instant kit, the microspheres further comprise polyethylene glycol (PEG). Where applicable, the embodiments described above for the instant method are also envisioned for this article of manufacture. In a preferred embodiment, the instant kit is supplied as a single-dose kit and contains (i) a single dose vial of finasteride-carrying biodegradable microspheres, and (ii) a single dose vial of diluent (e.g., sterile, clear liquid solution of 0.9% w / w sodium chloride, 0.5% - 1% w / w sodium carboxymethylcellulose, and 0.1% w / w polysorbate-80, or sterile liquid of medium-chain fatty acids). This invention further provides an article of manufacture comprising a syringe having therein the instant injectable formulation. Ideally, this article of manufacture is ready for use without further manipulation. Preferably, this syringe has a needle at least as thin as a 29 Gauge or 30 Gauge needle. This invention still further provides an article of manufacture comprising a dual chamber syringe having therein, in separate compartments, (a) a diluent, and (b) plurality of biodegradable microspheres, wherein the microspheres (i) have a d10value of at least 1 m and a d90 value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month, wherein the diluent and microspheres can be admixed within the syringe to form an injectable formulation immediately prior to use (e.g., within 30 minutes, 20 minutes, 10 minutes, five minutes, or one minute of use). Preferably, this dual chamber syringe has a needle at least as thin as a 29 Gauge or 30 Gauge needle. Where applicable, the embodiments described above for the instant method and instant kit are also envisioned for the above two syringe-based articles of manufacture. Finally, this invention provides a biodegradable microsphere, wherein the microsphere (i) has a diameter of from 1 m to 28 m (e.g., from 3 m to 25 m); (ii) comprises a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carries pharmaceutical finasteride; and (iv) when present intradermally, releases finasteride for at least one month. In one embodiment of the instant biodegradable microsphere, the microsphere has a lactic acid to glycolic acid molar ratio of from 100:0 to 50:50. In another embodiment, the microsphere (i) has a diameter of from 3 m to 25 m; and (ii) has a lactic acid to glycolic acid molar ratio of 75:25 or 85:15. In another embodiment, the microsphere further comprises polyethylene glycol (PEG). In a further embodiment, the microsphere, when present intradermally, releases finasteride for longer than one month. Preferably, the microsphere, when present intradermally, releases finasteride for at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, at least eleven months, or at least twelve months. Examples dutasteride PLGA refers to poly-lactic-co-glycolic acid; PDLA refers to poly-D-lactic acid, which is one kind of poly-lactic acid (PLA); DMSO refers to dimethyl sulfoxide; PVA refers to polyvinyl alcohol; PBS refers to phosphate buffered saline, pH 7.4; and MW refers to molecular weight. (i)_PLGA50:50, 0.2 dl / g, acid-terminated: Intrinsic viscosity = 0.16-0.24 dl / g. MW:7,000- 17,000; (ii) PLGA50:50, 0.2 dl / g, ester-terminated: Intrinsic viscosity = 0.16-0.24 dl / g. MW:7,000-17,000; (iii) PLGA50:50, 0.4 dl / g, acid-terminated: Intrinsic viscosity = 0.32- 0.44 dl / g. MW:24,000-38,000; (iv) PLGA50:50, 0.4 dl / g, ester-terminated: Intrinsic viscosity = 0.32-0.44 dl / g. MW:24,000-38,000; (v) PLGA50:50, 0.5 dl / g, acid-terminated: Intrinsic viscosity = 0.45-0.6 dl / g. MW:38,000-54,000; (vi) PLGA50:50, 0.5 dl / g, ester- terminated: Intrinsic viscosity = 0.45-0.6 dl / g. MW:38,000-54,000; (vii) PLGA50:50, 0.6 dl / g, ester-terminated: Intrinsic viscosity = 0.50-0.65 dl / g; (viii) PLGA50:50, 0.7 dl / g, ester-terminated: Intrinsic viscosity = 0.61-0.74 dl / g. MW:54,000-69,000; (ix) PLGA65:35, 0.4 dl / g, acid-terminated: Intrinsic viscosity = 0.32-0.44 dl / g. MW:24,000- 38,000; (x) PLGA75:25, 0.2 dl / g, acid-terminated: Intrinsic viscosity = 0.14-0.22 dl / g. MW: 4,000-15,000; (xi) PLGA75:25, 0.2 dl / g, ester-terminated: Intrinsic viscosity = 0.16- 0.24 dl / g. MW: 4,000-15,000; (xii) PLGA75:25, 0.4 dl / g, acid-terminated: Intrinsic viscosity = 0.32-0.44 dl / g. MW: 15,000-35,000; (xiii) PLGA75:25, 0.4 dl / g, ester- terminated: Intrinsic viscosity = 0.32-0.44 dl / g. MW: 15,000-35,000; (xiv) PLGA75:25, 0.6 dl / g, ester-terminated: Intrinsic viscosity = 0.5-0.7 dl / g. MW: 35,000-76,000 with average about 61,100; (xv) PLGA75:25, 0.65 dl / g, ester-terminated: Intrinsic viscosity = 0.55-0.75 dl / g. MW: about 97,000; (xvi) PLGA75:25, 0.9 dl / g, ester-terminated: Intrinsic viscosity = 0.71-1.0 dl / g. MW:76,000-115,000; (xvii) PLGA75:25, 1.1 dl / g, ester- terminated: Intrinsic viscosity = 0.9-1.3 dl / g. MW: 115,000-190,000; and (xviii) PLGA85:15, 1.5 dl / g, ester-terminated: Intrinsic viscosity = 1.3-1.7 dl / g. MW: 190,000- 240,000. In experiments described herein, one type of PVA (i.e., of one molecular weight and degree of hydrolysis) at one concentration (i.e., 1%) is used to produce microspheres. However, in this invention, other types of PVA and other PVA concentrations are also envisioned to yield the same microspheres. For example, where 0.11% PVA4-88, 200 l dichloromethane, and 1,400 rpm stirring, is used to produce a certain population of microspheres, 0.05% PVA4-88, 300 l dichloromethane, and 1,000 rpm stirring, may also be used to produce essentially the same population of microspheres. Surfactants other than PVA can also be used in this invention to produce microspheres. These other surfactants include, for example, the commonly known surfactants vitamin E, Tween-20, Tween-80, poloxamers, poloxamines, pluronic polymers (such as F68 and F127), and sodium cholate. Similarly, in experiments described herein, dichloromethane is used to produce microspheres. However, in this invention, other types of organic solvents (e.g., ethyl acetate, chloroform, acetone, propylene carbonate, and tetrahydrofuran) may be used instead of dichloromethane to yield essentially the same microspheres, assuming other experimental parameters are adjusted accordingly. Moreover, in this invention, any of a plurality of physical methods for preparing PLGA microspheres (e.g., spinning disk, spray drying, and microfluidics) may be used to yield the subject microspheres. 1 mg dutasteride and 1 mg PLGA75:25, 0.4 dl / g, acid-terminated were dissolved in 200 µl dichloromethane (DCM), or ethyl acetate (EA), or chloroform. The solution was injected into 50 ml 0.11% polyvinyl alcohol 4-88 (PVA4-88, Millipore Sigma, Darmstadt, Germany) and emulsified with a stir bar at 1,400 rpm for 2 minutes. In these reactions, EA and chloroform solutions resulted in microspheres with non-uniform distributions of encapsulated dutasteride, as visualized by light microscopy. Only DCM solution resulted in microspheres with uniform dutasteride distribution internally. The dutasteride microspheres formed from DCM solution were added to 40 ml ethanol to extract encapsulated dutasteride overnight. The concentration of extracted dutasteride in ethanol was determined by UV absorption at 210 nm and used to calculate the encapsulation efficiency in this reaction, which was 61.6%. In a separate experiment, 2 mg dutasteride and 1 mg PLGA75:25, 0.4 dl / g, acid- terminated were dissolved in 200 µl DCM, or EA, or chloroform. The solution was injected into 50 ml 0.11% PVA4-88 and emulsified with a stir bar at 1,400 rpm for 2 minutes. Similarly, only the DCM solution, but not EA or chloroform solutions, resulted in microspheres with uniform dutasteride distribution as visualized by light microscopy. Thus, DCM was selected as an appropriate organic solvent to prepare dutasteride microspheres. Example 2. Dutasteride release from microspheres made with a stir bar 1 mg dutasteride and 1 mg, or 2 mg, or 4 mg, or 9 mg, or 19 mg PLGA50:50, 0.1 dl / g, acid-terminated were dissolved in 200 µl DCM. The solution was injected into 50 ml 0.11% PVA4-88 and emulsified with a stir bar at 1,400 rpm for 2 minutes. Microspheres solidified after stirring the emulsion at 500 rpm for one hour and were washed in water twice. The microspheres were added to 250 ml water and shaken at 60 rpm at 37 C continuously. The concentration of released dutasteride into water was determined with UV absorption of the release solution at 210 nm. Every 3-5 days, 200 ml of release solution was replaced with 200 ml fresh water to maintain sink condition. In Figure 1, all formulations showed gaps in drug release, during which little dutasteride was released. Unexpectedly, most formulations did not completely release the encapsulated dutasteride even after two months, given that PLGA50:50, 0.1 dl / g, acid- terminated is typically degraded within one month. Due to the presence of gaps and incomplete release, these formulations are not suitable for treatment of hair loss. Example 3. Radiation stability of dutasteride microspheres In this study, dutasteride microspheres were prepared with a Silverson L5MA in-line mixing chamber (Silverson, Massachusetts, USA) (Figure 2). In the oil phase, 200 mg dutasteride and 200 mg PLGA75:25, 0.4 dl / g, acid-terminated were dissolved in 4 ml DCM and pumped into the mixing chamber at 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 1,000 ml / min. An emulsion was created with the mixing blade at 2,000 rpm and collected in a beaker to solidify under 500 rpm stirring for one hour. The microspheres were collected in between a 20 µm sieve and a 100 µm sieve, washed with water twice, and lyophilized. Aliquots of the lyophilized microspheres were further irradiated with 10 kGy, 15 kGy, 20 kGy, and 25 kGy E-beam, and the dutasteride contents from irradiated microspheres were compared against un-irradiated microspheres. Dutasteride content was analyzed with HPLC with a Zorbax SB-Phenyl 5-micron, 4.6 x 250 mm column (Agilent Technologies, California, US). About 10 mg of microspheres were dissolved in 0.5 ml DMSO and precipitated in 9.5 ml methanol for injection into HPLC (diluent: methanol; mobile phase: 50% acetonitrile in water; column temperature: 30 C; detection wavelength: 210 nm; flow rate: 4 ml / min; injection volume: 15 µl). Dutasteride content in the microspheres were 43.2%, 43.6%, 42.4%, 42.6%, and 43.0% for the un-irradiated, 10 kGy, 15 kGy, 20 kGy, and 25 kGy group, which suggests that encapsulated dutasteride was not degraded by up to 25 kGy of E-beam irradiation. 4. Dutasteride release from microspheres made in a mixing chamber 100 mg PLGA50:50, 0.1 dl / g, acid-terminated and 100 mg, or 50 mg, or 25 mg, or 10 mg, or 5 mg dutasteride were dissolved in 2 ml DCM to form the oil phase and pumped into the Silverson L5MA in-line mixing chamber at a rate of 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 800 ml / min. Emulsions were created with the mixing blade set at 2,000 rpm or 2,800 rpm and collected on top of 400 ml water stirred at 500 rpm in a beaker for one hour. The solidified microspheres were collected by centrifugation at 2,000 g for 5 minutes, washed in water twice, and lyophilized. Particle sizes of microspheres were determined with a laser-diffraction particle size analyzer (Beckman Coulter LS13320, New Jersey, US) and expressed as d10, d50, and d90 (Table 1). Table 1. Particle sizes of dutasteride microspheres Appropriate quantities of microspheres from each group (shown in table 1) were added to 250 ml water and shaken at 60 rpm at 37 C continuously. The concentration of released dutasteride into the solution was determined with UV absorption at 210 nm. Every 3-5 days, 200 ml of release solution was replaced with 200 ml fresh water to maintain sink condition. In Figure 3, dutasteride release was very slow after 30 days and there was significant incomplete release, except in the 5 mg dutasteride groups. Example 5. Dutasteride microspheres made from different PLGA types To study the effects of PLGA types on the release profile of dutasteride microspheres, multiple PLGA types were used in this study: PLGA50:50, 0.2 dl / g, acid-terminated; PLGA50:50, 0.4 dl / g, acid-terminated; PLGA75:25, 0.2 dl / g, acid-terminated; PLGA65:35, 0.4 dl / g, acid-terminated. 5-100 mg dutasteride and 100 mg PLGA were dissolved in 2 ml DCM to form the oil phase and pumped into the Silverson L5MA in-line mixing chamber at a rate of 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 800 ml / min. Emulsions were created with the mixing blade at 2,800 rpm and collected on top of 300 ml water under stirring at 500 rpm for one hour. The solidified microspheres were collected by centrifugation at 2,000 g for 5 minutes, washed with water twice, and lyophilized. Particle sizes of microspheres were determined with a laser-diffraction particle size analyzer (Beckman Coulter LS13320, New Jersey, US) (Table 2). Appropriate quantities of microspheres from each group (shown in table 2) were added to 250 ml water and shaken at 60 rpm at 37 C continuously. The concentration of released dutasteride into the solution was determined with UV absorption at 210 nm. Every 3-5 days, 200 ml of release solution was replaced with 200 ml fresh water to maintain sink condition. Figure 4 shows significant incomplete dutasteride release, except in the 5 mg dutasteride groups.

[0003] Table 2. Particle sizes of dutasteride microspheres 6. In vivo release of dutasteride Dawley rats 100 mg dutasteride and 2 g PLGA75:25, 0.2 dl / g, acid-terminated were dissolved in 40 ml DCM to form the oil phase and pumped into a Silverson L5MA in-line mixing chamber at 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 800 ml / min. An emulsion was created by the mixing blade at 2,800 rpm and collected in a beaker under stirring at 500 rpm for one hour. The solidified microspheres were filtered through a 63 µm sieve to remove large particulates and collected on a 5 µm PTFE membrane in a vacuum filtration flask. The microspheres were washed with water twice and lyophilized. Particle sizes of microspheres were determined with a laser-diffraction particle size analyzer (Beckman Coulter LS13320, New Jersey, US). The d10, d50, and d90values were 7.9 µm, 13.9 µm, and 22.6 µm, respectively. Dutasteride content was analyzed with HPLC with a Zorbax SB-Phenyl 5-micron, 4.6 x 250 mm column (Agilent Technologies, California, US). About 10 mg of microspheres were dissolved in 1 ml DMSO and precipitated in 9 ml methanol for injection into HPLC (diluent: methanol; mobile phase: 50% acetonitrile in water; column temperature: 30 C; detection wavelength: 210 nm; flow rate: 4 ml / min; injection volume: 15 µl). The drug loading ratio of dutasteride in this microsphere was 3.9%. 250 mg of the microsphere was injected subcutaneously to the scalp of three replicate male Sprague Dawley rats. Plasma samples were collected over 70 days to determine dutasteride concentrations in the plasma with an LC-MS / MS system (SHIMADZU LC40, Triple Quad 6500+ with Analyst 1.7.2 AB Sciex). Table 3 shows continuous dutasteride release from microspheres in the rats over at least six weeks. Table 3. Plasma dutasteride concentration after subcutaneous injection of microspheres 1 mg finasteride and 1 mg PLGA75:25, 0.4 dl / g, acid-terminated were dissolved in 200 µl DCM, or EA, or chloroform. The solution was injected into 50 ml 0.11% PVA4-88 and emulsified with a stir bar at 1,400 rpm for 2 minutes. In these reactions, microspheres formed from the solutions of DCM and chloroform, but not EA. The finasteride microsphere formed from DCM solution was added to 40 ml ethanol to extract encapsulated finasteride overnight. The concentration of extracted finasteride in ethanol was determined by UV absorption at 210 nm and used to calculate the encapsulation efficiency in this reaction, which was 77.0%. In a separate experiment, 2 mg finasteride and 1 mg PLGA75:25, 0.4 dl / g, acid- terminated were dissolved in 200 µl DCM, EA, or chloroform. The solution was injected into 50 ml 0.11% PVA4-88 and emulsified with a stir bar at 1,400 rpm for 2 minutes. In these reactions, only the DCM solution generated finasteride microspheres successfully. Thus, DCM was selected as an appropriate organic solvent to prepare finasteride microspheres. Example 8. Drug release from short-acting finasteride microspheres prepared with a stir bar 1 mg finasteride and 1 mg PLGA were dissolved in 200 µl DCM, and this solution was injected into 50 ml 0.11% PVA4-88 and emulsified with a stir bar at 1,400 rpm for 2 minutes. This emulsion was further stirred at 500 rpm for 20 minutes to solidify the microspheres, which were washed in water twice. PLGA used in this study included: PLGA50:50, 0.1 dl / g, acid-terminated; PLGA50:50, 0.2 dl / g, acid-terminated; PLGA50:50, 0.4 dl / g, acid-terminated. To monitor finasteride release, the microspheres were added to 250 ml water and shaken at 60 rpm at 37 C continuously. The concentration of released finasteride into the solution was determined with UV absorption at 210 nm. In Figure 5, all microspheres showed finasteride release within one month. Example 9. Drug release from long-acting finasteride microspheres prepared with a stir bar To increase the release duration of microspheres, PLGA with higher L:G ratio, higher inherent viscosity, and ester end caps were studied. 1 mg finasteride and 1 mg PLGA were dissolved in 200 µl DCM, and this solution was injected into 50 ml 0.11% PVA4-88 and emulsified with a stir bar at 1,400 rpm for 2 minutes. This emulsion was further stirred at 500 rpm for 20 minutes to solidify the microspheres, which were washed in water twice. PLGA used in this study included: PLGA50:50, 0.5 dl / g, acid-terminated; PLGA65:35, 0.4 dl / g, acid-terminated; PLGA75:25, 0.4 dl / g, acid-terminated; PLGA75:25, 0.6 dl / g, ester-terminated. To monitor finasteride release, the microspheres were added to 250 ml water and shaken at 60 rpm at 37 C continuously. The concentration of released finasteride in the solution was determined with UV absorption at 210 nm. Every 3-4 weeks, 200 ml of release solution was replaced with 200 ml of fresh water to maintain sink condition. In Figure 6, all microspheres showed finasteride release for at least one month. Notably, microspheres from PLGA75:25, 0.4 dl / g, acid-terminated showed continuous finasteride release over two months. Microspheres from PLGA75:25, 0.6 dl / g, ester- terminated showed continuous release from day 60 to beyond day 155, but there was a long gap in drug release between 30 to 60 days, which is undesirable for the continuous treatment of hair loss. Particle sizes of microspheres were determined with a laser-diffraction particle size analyzer (Beckman Coulter LS13320, New Jersey, US). The d10, d50 and d90 values of microspheres from PLGA75:25, 0.4 dl / g, acid-terminated was 14.7 µm, 30.4 µm, and 40.5 µm respectively. The d10, d50and d90values of microspheres from PLGA75:25, 0.6 dl / g, ester-terminated was 18.7 µm, 31.4 µm, and 41.2 µm, respectively. Example 10. Effects of increasing finasteride:PLGA ratio in long-acting finasteride microspheres 1 mg finasteride and 1 mg or 0.8 mg or 0.6 mg PLGA75:25, 0.6 dl / g, ester-terminated were dissolved in 200 µl DCM, and this solution was injected into 50 ml 0.11% PVA4-88 and emulsified with a stir bar at 1,400 rpm for 2 minutes. This emulsion was further stirred at 500 rpm for 20 minutes to solidify the microspheres, which were washed in water twice. To monitor finasteride release, the microspheres were added to 250 ml water and shaken at 60 rpm at 37 C continuously. The concentration of released finasteride in the solution was determined with UV absorption at 210 nm. Every 3-4 weeks, 200 ml of release solution was replaced with 200 ml of fresh water to maintain sink condition. In Figure 7, the microspheres made from 1 mg finasteride and 0.6 mg PLGA showed very high burst release, with 40-70% of cumulative release over the initial 15 days. This burst release increases the risk of systemic toxicity to patients and thus this group was excluded from later discussions. In the microspheres made from 1 mg finasteride and 0.8-1 mg PLGA, burst release was modest and all microspheres made from mixed PLGA showed release over 1-3 months. However, a long gap phase over 30 days where little finasteride was released still existed for the PLGA75:25, 0.4 dl / g, acid- terminated:PLGA75:25, 0.6 dl / g, ester-terminated=25:75 formulations, which is undesirable for continuous treatment of hair loss. By mixing two different types of PLGA, the resulting microsphere typically shows release duration that is in between the respective durations from each single type of PLGA. Unexpectedly, the PLGA75:25, 0.4 dl / g, acid-terminated:PLGA75:25, 0.6 dl / g, ester- terminated=75:25 formulations showed shorter durations and faster drug release than either the pure PLGA75:25, 0.4 dl / g, acid-terminated or the pure PLGA75:25, 0.6 dl / g, ester-terminated formulations. Example 11. Preparing finasteride microsphere in a mixing chamber 200 mg finasteride and 200 mg or 160 mg PLGA were dissolved in 4 ml DCM to form the oil phase, which was pumped into a Silverson L5MA in-line mixing chamber at a rate of 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 1,000 ml / min. Emulsions were created by the mixing blade at 2,000 rpm or 2,800 rpm and were collected on top of 250 ml water under stirring at 500 rpm for one hour. The solidified microspheres were filtered with a 63 µm sieve to remove large particulates and collected by centrifugation at 4,000 g for 5 minutes. The microspheres were then washed with water twice and lyophilized. PLGA used in this study included pure and mixed polymers of PLGA75:25, 0.4 dl / g, acid-terminated and PLGA75:25, 0.6 dl / g, ester-terminated. Particle sizes of microspheres were determined with a laser-diffraction particle size analyzer (Beckman Coulter LS13320, New Jersey, US) (Table 4). To monitor finasteride release, 5 mg microspheres were added to 250 ml water, and shaken at 60 rpm at 37 C continuously. The concentration of released finasteride in the solution was determined with UV absorption at 210 nm. Every 3-4 weeks, 200 ml of release solution was replaced with 200 ml of fresh water to maintain sink condition. Unexpectedly, all microspheres showed continuous finasteride release over two months, with similar release rates between microspheres made with 2,000 rpm and 2,800 rpm (Figure 8). Table 4. Particle sizes of finasteride microspheres. size on finasteride release 100 mg finasteride and 100 mg or 80 mg PLGA75:25, 0.4 dl / g, acid-terminated were dissolved in 2 ml DCM to form the oil phase, and pumped into the Silverson L5MA in- line mixing chamber at 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 800 ml / min. Emulsions were created with the mixing blade at 2,000 rpm, 2,800 rpm, 3,200 rpm, or 3,600 rpm, and were collected on top of 400 ml water under stirring at 500 rpm for one hour. The solidified microspheres were collected by centrifugation at 4,000 g for 5 minutes, washed in water twice, and lyophilized. Particle sizes of microspheres were determined with a laser-diffraction particle size analyzer (Beckman Coulter LS13320, New Jersey, US) (Table 4). To monitor finasteride release, 5 mg microspheres were added to 250 ml water, and shaken at 60 rpm at 37 C continuously. The concentration of released finasteride in the solution was determined with UV absorption at 210 nm. Every 3-4 weeks, 200 ml of release solution was replaced with 200 ml of fresh water to maintain sink condition. Finasteride content in the microspheres was analyzed with HPLC with a Zorbax SB- Phenyl 5-micron, 4.6 x 250 mm column (Agilent Technologies, California, US). About 10 mg of microspheres were dissolved in 1 ml DMSO and precipitated in 9 ml methanol for injection into HPLC (diluent: methanol; mobile phase: 50% acetonitrile in water; column temperature: 30 C; detection wavelength: 210 nm; flow rate: 3.5 ml / min; injection volume: 10 µl). Drug loading was calculated as finasteride content / total weight of microspheres, and encapsulation efficiency was calculated as actual drug loading / theoretical drug loading predicted by quantity of input materials (Table 5). Figure 9 shows continuous finasteride release over two months across all formulations. Unexpectedly, formulations at 2,000 rpm showed significant burst release on day 1, much greater than formulations at 2,800 rpm, 3,200 rpm and 3,600 rpm, which had smaller particle sizes typically associated with greater burst release. Furthermore, reducing particle size from the 2,800 rpm formulations to 3,600 rpm formulations had little effect on total duration of finasteride release, even though smaller particle sizes are typically associated with a shorter duration of release. Smaller microspheres can be injected with smaller needles, which are desired for scalp injections in patients with hair loss. In this example, a reduction of microsphere size could greatly improve patient experience by reducing injection site pain without affecting the duration of finasteride release. Table 5. Particle sizes and drug loading of finasteride microspheres Example 13. Effects of E-beam irradiation on release of finasteride microspheres 200 mg finasteride and 200 mg or 160 mg PLGA were dissolved in 4 ml DCM to form the oil phase, and pumped into a Silverson L5MA in-line mixing chamber at 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 800 ml / min. Emulsions were created with the mixing blade at 3,600 rpm and collected on top of 800 ml water under stirring at 500 rpm for one hour. The solidified microspheres were filtered through a 63 µm sieve and collected on a 5 µm PTFE membrane in a vacuum filter flask. The microspheres were washed with water twice, lyophilized, and irradiated with 15 kGy E-beam. PLGA used in this study was shown in table 6. Particle sizes of microspheres were determined with a laser-diffraction particle size analyzer (Beckman Coulter LS13320, New Jersey, US) (Table 6). To monitor finasteride release, 5 mg microspheres were added to 250 ml water, and shaken at 60 rpm at 37 C continuously. The concentration of released finasteride in the solution was determined with UV absorption at 210 nm. Every 3-4 weeks, 200 ml of release solution was replaced with 200 ml of fresh water to maintain sink condition. Finasteride content in the microspheres was analyzed with HPLC with a Zorbax SB- Phenyl 5-micron, 4.6 x 250 mm column (Agilent Technologies, California, US). About 10 mg of microspheres were dissolved in 1 ml DMSO and precipitated in 9 ml methanol for injection into HPLC (diluent: methanol; mobile phase: 50% acetonitrile in water; column temperature: 30 C; detection wavelength: 210 nm; flow rate: 3.5 ml / min; injection volume: 10 µl) (Table 6). Figure 10 shows continuous finasteride release over three months for formulations #13- 3, #13-4, #13-5, #13-6, #13-7, #13-8, #13-14, #13-15, and #13-16, and over four months for formulations #13-9, #13-10, #13-17, #13-18, #13-19, and #13-20. Unexpectedly, higher finasteride drug loading slightly prolonged the total duration of release even though higher drug loading is typically associated with a shorter duration of release. Table 6. Finasteride loading ratios and particle sizes of microspheres after 15 kGy E- beam. Example 14. In vivo finasteride release from E-beam-irradiated in 600 mg finasteride and 480 mg PLGA were dissolved in 12 ml DCM to form the oil phase, and pumped into the Silverson L5MA in-line mixing chamber at 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 800 ml / min. Emulsions were created by the mixing blade at 4,400 rpm and collected on top of 2 L water under stirring at 500 rpm for 30 minutes. The solidified microspheres were filtered with a 45 µm sieve to remove large particulates and collected on a 5 µm PTFE membrane in a vacuum filter flask. The microspheres were washed with water twice, lyophilized, and irradiated with 15 kGy E-beam. Particle sizes of microspheres were determined with a laser-diffraction particle size analyzer (Beckman Coulter LS13320, New Jersey, US) (Table 7). To monitor finasteride release, 20 mg microspheres were added to 250 ml phosphate buffered saline (PBS, pH=7.4), and shaken at 60 rpm at 37 C continuously. The concentration of released finasteride in the solution was determined with UV absorption at 230 nm. Every 3-4 weeks, 200 ml of release solution was replaced with 200 ml of fresh PBS to maintain sink condition. Finasteride content in the microspheres was analyzed with HPLC with a Zorbax SB- Phenyl 5-micron, 4.6 x 250 mm column (Agilent Technologies, California, US). About 10 mg of microspheres were dissolved in 1 ml DMSO and precipitated in 9 ml methanol for injection into HPLC (diluent: methanol; mobile phase: 50% acetonitrile in water; column temperature: 30 C; detection wavelength: 210 nm; flow rate: 3.5 ml / min; injection volume: 10 µl) (Table 7). Figure 11 shows continuous release of all microsphere formulations in vitro from three months to over six months. 200 mg of each microsphere was injected subcutaneously to the scalp of a male Sprague Dawley rat, and 300 mg of each microsphere was injected subcutaneously to the scalp of a male Beagle dog. Plasma samples were collected over 238 days and finasteride concentrations in the plasma were determined with an LC-MS / MS system (SHIMADZU LC40, Triple Quad 6500+ with Analyst 1.7.2 AB Sciex). Table 8 shows continuous release of finasteride from microspheres in rats and dogs for three months, four months, five months, and seven months. Table 7. Particle sizes and finasteride drug loading of microspheres Table 8. Plasma finasteride concentrations after microsphere injections in rats and dogs Example 15. Syringeability and injectability test of microspheres from Example 14 Smaller needle sizes cause less injection site pain. The scalp is rich in sensory nerves, which makes a small needle size crucial for improving patient experience and compliance to long-term treatment of hair loss. A diluent for the microsphere was prepared as 0.9% sodium chloride, 0.5% carboxymethyl cellulose, and 0.1%polysorbate 80 in water. When 200 mg of microspheres from Example 14 wasresuspended in 0.5 ml to 1 ml of diluent, the suspension was easily able to bewithdrawn and injected with a 29 Gauge or 30 Gauge needle (external diameters of0.34-0.31 mm) without clogging. These needle sizes are FDA-approved for Botoxinjections to the scalp to treat chronic migraine and for Botox injections to the face totreat wrinkles and are thus widely accepted by healthcare professionals and patients.In this Example, the finasteride microspheres passed through 29-gauge and 30-gaugeneedles, although a 27-gauge or 28-gauge needle may also be used clinically.Example 16. In vivo finasteride release from un-irradiated microspheres in Sprague Dawley rats and Beagle dogs 2.4 g finasteride and 1.92 g PLGA75:25, 0.9 dl / g, ester-terminated or PLGA85:15, 1.5dl / g, ester-terminated were dissolved in 48 ml DCM to form the oil phase, and pumpedinto the Silverson L5MA in-line mixing chamber at 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 800 ml / min. Emulsions were createdby the mixing blade at 4,400 rpm and collected on top of 10 L water under stirring at 500rpm for 30 minutes. The solidified microspheres were filtered with a 45 µm sieve to remove large particulates and collected on a 5 µm PTFE membrane in a vacuum filterflask. The microspheres were washed with water twice and lyophilized.Particle sizes of microspheres were determined with a laser-diffraction particle sizeanalyzer (Beckman Coulter LS13320, New Jersey, US) (Table 9). Finasteride content in the microspheres was analyzed with HPLC with a Zorbax SB-Phenyl 5-micron, 4.6 x 250 mm column (Agilent Technologies, California, US). About 10 mg of microspheres were dissolved in 1 ml DMSO and precipitated in 9 ml methanol for injection into HPLC (diluent: methanol; mobile phase: 50% acetonitrile in water; column temperature: 30 C; detection wavelength: 210 nm; flow rate: 3.5 ml / min; injection volume: 10 µl) (Table 9). 200 mg of each microsphere was injected subcutaneously to the scalp of a male Sprague Dawley rat, and 600 mg of each microsphere was injected subcutaneously tothe scalp of a male Beagle dog. Plasma samples were collected over 280 days andfinasteride concentrations in the plasma were determined with an LC-MS / MS system(SHIMADZU LC40, Triple Quad 6500+ with Analyst 1.7.2 AB Sciex). Table 10 showscontinuous release of finasteride from microspheres for over seven months for PLGA75:25, 0.9 dl / g, ester-terminated and over nine months for PLGA85:15, 1.5 dl / g, ester-terminated.Table 9. Particle sizes and finasteride drug loading of microspheres

[0004] Table 10. Plasma finasteride concentrations after microsphere injections in rats anddogs (PLGA75:25, 0.9 dl / g, ester-terminated and PLGA85:15, 1.5 dl / g, ester-terminated) on finasteride release from Appropriate quantities of finasteride and PLGA were dissolved in 36 ml or 40 ml DCM toform the oil phase, and pumped into the Silverson L5MA in-line mixing chamber at 4 ml / min. The water phase of 0.11% PVA4-88 was pumped into the mixing chamber at 800 ml / min. Emulsions were created by the mixing blade at 4,400 rpm and collected on top of 8 L water under stirring at 500 rpm for 30 minutes. The solidified microspheres were filtered with a 45 µm sieve to remove large particulates and collected on a 5 µm PTFE membrane in a vacuum filter flask. The microspheres were washed with watertwice and lyophilized. Some microspheres were irradiated with 25 kGy E-beam.Microsphere formulations are shown in Table 11.Particle sizes of microspheres were determined with a laser-diffraction particle sizeanalyzer (Beckman Coulter LS13320, New Jersey, US) (Table 11). Finasteride content in the microspheres was analyzed with HPLC with a Zorbax SB-Phenyl 5-micron, 4.6 x 250 mm column (Agilent Technologies, California, US). About 10 mg of microspheres were dissolved in 1 ml DMSO and precipitated in 9 ml methanol for injection into HPLC (diluent: methanol; mobile phase: 50% acetonitrile in water; column temperature: 30 C; detection wavelength: 210 nm; flow rate: 3.5 ml / min; injection volume: 10 µl) (Table 11).Table 11. Formulation, particle sizes and drug loading of finasteride microspheres. To monitor in vitro finasteride release, 20 mg of microspheres were added to 250 mlPBS (pH=7.4) and shaken at 60 rpm at 37 C continuously. The concentration ofreleased finasteride in the solution was determined with HPLC with a Zorbax SB-Phenyl5-micron, 4.6 x 250 mm column (Agilent Technologies, California, US) (Mobile phase:ACN:H2O=50:50, flow rate: 3.5 ml / min, injection volume: 100 µl, column temperature: 30 C, detection wavelength: 210 nm, approximate retention time: 3.3 min).Figures 12A-E show continuous release of all tested microspheres over six months.Un-irradiated microspheres (17-1 to 17-4, 17-9 to 17-16) were injected subcutaneouslyto a male Sprague Dawley rat at a dose of 200 mg microspheres. Plasma sampleswere collected over 98 days and finasteride concentrations in the plasma weredetermined with an LC-MS / MS system (SHIMADZU LC40, Triple Quad 6500+ with Analyst 1.7.2 AB Sciex). Table 12 shows continuous finasteride release for all tested microspheres. Unexpectedly, formulations with lower drug loading (17-1 to 17-4)showed a peak level around day 42, and formulations with high drug loading (17-13 to17-16) showed a peak level around day 28. Only formulations 17-9 and 17-10 withintermediate drug loading showed relatively smooth finasteride concentration and astable drug release rate across 98 days. Fluctuations in plasma drug concentration are correlated with greater side effects, and thus the stable release profile of formulations17-9 and 17-10 are highly desirable for long-acting drugs. These data suggest thatPLGA75:25, 0.5-1.3 dl / g, ester-terminated with 30-35% finasteride loading and having ad10 value of at least 3 m and a d90 value of 25 m or less are one optimal combinationof formulation parameters. Table 12. Plasma finasteride concentrations after microsphere injections in rats

[0005] References FDA label of Propecia®(finasteride). FDA label of Botox®. FDA label of Botox®Cosmetic. FDA label of Lupron®. Kang, et al. (2021) Pharmacokinetic-pharmacodynamic modeling approach for dose prediction of the optimal long-acting injectable formulation of finasteride. International Journal of Pharmaceutics.601. Kim, et al. (2021) Three months extended-release microspheres prepared by multi- microchannel microfluidics in beagle dog models. International Journal of Pharmaceutics.608. Kim, et al. (2019) Development of finasteride polymer microspheres for systemic application in androgenic alopecia. International Journal of Molecular Medicine. 43:2409-2419. Moon, et al., WO 2024 / 019596. Sustained-release formulation containing 5-alpha reductase inhibitor.

Claims

Claims What is claimed is:

1. A plurality of biodegradable microspheres, wherein the microspheres (i) have a d10value of at least 1 m and a d90value of 28 m or less; (ii) comprise a polylactic-co- glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month.

2. The plurality of biodegradable microspheres of claim 1, wherein the microspheres further comprise polyethylene glycol (PEG).

3. The plurality of biodegradable microspheres of claim 1 or 2, wherein the microspheres, when present intradermally, release finasteride for at least two months.

4. The plurality of biodegradable microspheres of any of claims 1-3, wherein the microspheres (i) have a d10value of at least 3 m and a d90value of 25 m or less; (ii) have a lactic acid to glycolic acid molar ratio of from 100:0 to 50:50; and (iii) carry from 1 g to 3,000 mg of pharmaceutical finasteride.

5. An injectable formulation comprising (a) a pharmaceutically acceptable carrier and (b) a plurality of biodegradable microspheres wherein the microspheres (i) have a d10 value of at least 1 m and a d90 value of 28 m or less; (ii) comprise a polylactic-co- glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month.

6. The formulation of claim 5, wherein the microspheres further comprise polyethylene glycol (PEG).

7. The formulation of claim 5 or 6, wherein the microspheres, when present intradermally, release finasteride for at least two months.

8. A method for treating hair loss in a subject comprising introducing biodegradable microspheres into an affected area of the subject’s skin, wherein the introducing is into skin at or around one or more hair follicles, and wherein the microspheres (i) have a d10value of at least 1 m and a d90 value of 28 m or less; (ii) comprise a polylactic-co- glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month.

9. The method of claim 8, wherein the microspheres further comprise polyethylene glycol (PEG).

10. The method of claim 8 or 9, wherein the subject is human.

11. The method of any of claims 8-10, wherein the microspheres (i) have a d10 value of at least 3 m and a d90value of 25 m or less; (ii) have a lactic acid to glycolic acid molar ratio of from 100:0 to 50:50; and (iii) carry from 1 g to 3,000 mg of pharmaceutical finasteride.

12. The method of any of claims 8-11, wherein the microspheres have an average lactic acid to glycolic acid molar ratio of 75:25 or 85:

15.

13. The method of any of claims 8-12, wherein the microspheres release finasteride for at least two months.

14. The method of any of claims 8-13, wherein the microspheres release finasteride for at least three months.

15. The method of any of claims 8-14, wherein the microspheres release finasteride for at least six months.

16. A kit comprising, in separate compartments, (a) a diluent, and (b) plurality of biodegradable microspheres, wherein the microspheres (i) have a d10 value of at least 1 m and a d90 value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceuticalfinasteride; and (iv) when present intradermally, release finasteride for at least one month.

17. An article of manufacture comprising a syringe having therein the injectable formulation of any of claims 5-7.

18. An article of manufacture comprising a dual chamber syringe having therein, in separate compartments, (a) a diluent, and (b) plurality of biodegradable microspheres, wherein the microspheres (i) have a d10value of at least 1 m and a d90value of 28 m or less; (ii) comprise a polylactic-co-glycolic acid copolymer (PLGA) matrix; (iii) carry a therapeutically effective amount of pharmaceutical finasteride; and (iv) when present intradermally, release finasteride for at least one month, wherein the diluent and microspheres can be admixed within the syringe to form an injectable formulation immediately prior to use.

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