Sildenafil-chitosan nanocomplexes in rosemary-infused smart emulgel: Sustainable drug delivery with improved hair regeneration efficacy

Hair loss, a prevalent dermatological condition with profound psychosocial impacts, arises from genetic, hormonal, environmental, and pathological factors. This study developed sildenafil-loaded chitosan nanocomplexes using varying molar ratios (1:2, 1:1, 2:1) of chitosan HCl (CHC) and carboxymethyl chitosan (CMCH) at concentrations of 2, 4, and 6 mM. The nanocomplexes were characterized for particle size, polydispersity index (PDI), zeta potential, drug loading, and in-vitro drug release. The optimal nanocomplex (C5) composed of 1:1 CHC:CMCH (4 mM) exhibited a particle size of 218.9 nm, PDI of 0.1, zeta potential of +20.2 mV, and drug loading of 65.8 %, with a sustained drug release (T50 = 12.1 h; T90 = 38.5 h). A smart thermosensitive emulgel, which remained liquid at room temperature and gelled at scalp temperature, was prepared using poloxamer 407 (14.5 % w/v) and poloxamer 188 (5.5 % w/v) (total poloxamer: 20 % w/v) and 10 % w/v rosemary oil which was phytochemically characterized by GC/MS analysis. The major constituents identified in the oil were camphor (17.82 ± 1.98 %), 1,8-cineole (12.56 ± 2.14 %), and borneol (10.01 ± 1.44 %). The selected nanocomplex (C5) was incorporated into the emulgel and evaluated for hair growth in C57BL/6 mice over 12 days, compared to minoxidil market product. The selected C5-loaded emulgel demonstrated comparable efficacy to the market product containing minoxidil, with superior hair regeneration, significant upregulation of p-PI3K and VEGF, and marked downregulation of TGF-β. This study presents an innovative, aesthetically acceptable topical sildenafil formulation that leverages chitosan nanocomplexes and rosemary oil to enhance follicular delivery and prolong therapeutic action. This approach offers a promising non-invasive alternative for alopecia therapy.