Ionic liquid-coated Eudragit RS nanoparticles for topical delivery of honokiol to remodel the hair follicle microenvironment in androgenic alopecia.

Androgenic alopecia (AGA) is a progressive hair loss condition caused by androgen-induced follicular miniaturization and hair growth signaling pathway impairment. Ineffective targeting of the pilosebaceous units and insufficient dermal retention limit the effectiveness of available topical therapies, emphasizing the need to explore more advanced treatment options. Honokiol (HK), a natural biphenolic compound, has proven to possess hair regeneration and anti-androgenic properties through modulation of key signaling pathways related to hair growth, specifically the activation of Wnt /β-catenin and suppression of transforming growth factor (TGF-β). However, its application is limited because of its poor bioavailability upon oral administration. The cutting-edge nanotechnology offers innovative tools for boosting drug effectiveness. Eudragit RS-based polymeric nanoparticles showed high efficacy for topical controlled release. In this study, HK-loaded Eudragit RS nanoparticles (HKE) were synthesized using the nanoprecipitation technique. A three-factor, three-level Box-Behnken Design optimized formulation parameters. To achieve enhanced follicular deposition, the optimized formula (HKEopt) was coated with choline geranate (CAGE), a green solvent that is known for its ability to enhance dermal penetration and drug deposition. Physicochemical characterization included morphology, particle dimensions (PS), surface charge (ZP), entrapment efficiency (EE), and in vitro release. HKEopt resulted in a mean PS of 63.88 nm, a strongly positive ZP (+41.05), high EE (87.5%), and sustained drug release. The ionic liquid coating reduced the ZP to +2.98 mV and increased PS to 91.58 nm, confirming surface modification. The synthesized coat was further validated with the TEM micrograph and FT-IR charts. In vivo evaluation demonstrated enhanced hair growth, accompanied with activation of the Wnt/β-catenin pathway and downregulation of the TGF-β, which was more pronounced with the coated nanoparticles. These findings suggested that the ionic liquid modified polymeric nanoparticles represent a promising scalable platform for the topical delivery of HK in AGA.