Controlled release 3D nanofiber scaffolds for fostering the anti-acne effect of spironolactone in an in vivo surgical testosterone-induced acne model

Controlled-release electrospun nanofiber (NF) scaffolds offer a promising delivery system for spironolactone (SP) to improve its proven oral anti-acne repurposed use and overcome its systemic side effects. In the present study, eight different Polycaprolactone (PCL) polymeric solutions were electrospun into NFs. The best formula (PCL-h NFs) was further loaded with SP (SP-PCL NFs). Scanning electron microscopy showed that the PCL-h NFs scaffold has the smoothest homogeneous surface compared to the other formulae, with an average fiber diameter of 500 nm. SP-PCL NFs maintained structural uniformity, and their diameter size showed no significant change. The surface roughness of PCL-h NFs and SP-PCL NFs was analyzed using atomic force microscopy, revealing that Ra 138.5 nm for PCL-h NFs and Ra 97.72 nm for SP-PCL NFs. Additional characterizations, including solid state, water contact angle, swelling tests, and mechanical study, were also conducted. The in vitro release study for SP-PCL NFs showed an improvement in SP amount released compared to the pure SP, and the pattern of SP release from SP-PCL NFs was a minor initial burst release followed by more steady controlled release till 168 h. Skin deposition study demonstrated that SP-PCL NFs achieved 8.5 times drug retention compared to the pure SP gel. The In vivo testosterone-induced acne model in mice showed the efficacy of SP-PCL NFs as antiandrogenic NFs, as SP-PCL NFs reduced sebocyte proliferation and total sebaceous tissue volume in mice compared to PCL NFs and pure SP gel. In conclusion, these results suggest potential therapeutic applications for treating androgen-related acne through its anti-androgenic activity.