Preparation of topical bimatoprost with enhanced skin infiltration and in vivo hair regrowth efficacy in androgenic alopecia

Drug Deliv. 2022 Dec;29(1):328-341. doi: 10.1080/10717544.2022.2027046.

Abstract

To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM-TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM-TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 μM BIM, equivalent to 10 μM minoxidil. Moreover, BIM-TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM-TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM-TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM-TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.

Keywords: Bimatoprost; alopecia; hair follicles; hair growth; highly skin-permeable; prostaglandins; supersaturated topical delivery system.

MeSH terms

  • Administration, Topical
  • Alopecia / pathology*
  • Animals
  • Antioxidants / chemistry
  • Bimatoprost / administration & dosage
  • Bimatoprost / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • Hair / drug effects*
  • Hair Follicle / drug effects*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Minoxidil / pharmacology
  • Skin Absorption / drug effects
  • Skin Absorption / physiology
  • Solvents / chemistry

Substances

  • Antioxidants
  • Solvents
  • Minoxidil
  • Bimatoprost

Grants and funding

This research was supported by the Basic Research Program through the National Research Foundation of Korea (NRF), funded by the Korean Government Ministry of Science and ICT (MSIT) [Grant No. NRF-2020R1F1A1069889].