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

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.

Topical Delivery of Atraric Acid Derived from Stereocaulon japonicum with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia

“…Drug solubility within a vehicle system is the most important factor when selecting volatile topical formulations, as it can enhance drug infiltration into deep skin layers. The excess solid method was used to examine the solubility of AA in various hydroalcoholic solvents (ethanol, isopropyl alcohol, benzyl alcohol, propylene glycol, and Transcutol P), lipophilic solvents (isopropyl myristate, caprylic triglyceride, oleic acid, glycerin, and cyclomethicone), and non-ionic surfactants (Capryol 90, PEG 400, Tween 20, and Tween 80) [ 45 ]. Briefly, 0.5 g of each solvent was vortex mixed with 10 mg of AA in a sealed glass container.…”

“…The SC was isolated by tape-stripping the skin 35 times with D-Squame (CuDerm, Dallas, TX, USA) [ 46 , 47 ]. Then the epidermis and dermis were separated, and the remaining skin was immersed overnight in 5 mL of ice-cold dispase solution [0.5% ( w / v )] [ 45 ]. The isolated SC, epidermis, and dermis layers were cut into small pieces and the drug retained in each layer was extracted with ethanol (2 mL).…”

The physiological and pharmacological roles of prostaglandins in hair growth

“…Recently, Subedi et al . [ 59 ] prepared a topical formulation of bimatoprost having high skin permeability ( Table 1 ). They designed a solvent mixture system, which contained ethanol, cyclomethicone, diethylene glycol monoethyl ether, and butylated hydroxyanisole.…”

“…This 5% bimatoprost formulation significantly increased the hair weight by 8.45- and 1.30-fold compared to the 5% bimatoprost in ethanol and 5% minoxidil-treated groups, respectively. This 5% bimatoprost formulation also remarkably enhanced the number and diameter of hair follicles compared to the vehicle-treated mice or 5% (w/w) bimatoprost in the ethanol-treated group [ 59 ]. The clinical application of bimatoprost to the treatment of AGA is also needed.…”

Formulation and Development of Adapalene Topical Nanohydrogel Using Different Surfactants and Cosurfactants for Antiacne Activity: In Vitro and Ex Vivo Evaluation

“…Generally, it is assumed that penetration enhancers like nonionic surfactants excrete into the intercellular lipid bilayers of skin therefore diminishing the crystalline characteristics of these lipid bilayers' crystallinity and intensifying their permeation potentiality [55]. Furthermore, the alternate mode of action associated with nonionic surfactants is the promotion of sebum emulsification and therefore elevate drug thermodynamic activity [56,57]. The prompt and higher ADP penetration via the skin is mainly because the formulation of NH-Tween-80 can elaborate with different mechanisms.…”