Synergistic chitosan nanoparticles loaded with baricitinib for the management of persistent chemotherapy-induced alopecia.

Chemotherapy-induced alopecia (CIA) represents a significant psychological burden for cancer patients, with permanent or persistent CIA (pCIA) posing an irreversible challenge due to the severe hair follicle damage resulting from some cytotoxic agents. Therefore, prophylactic strategies are urgently needed to protect hair follicles from cytotoxic insults. The current study aimed to develop and characterize baricitinib loaded chitosan nanoparticles for topical delivery, leveraging baricitinib' s anti-inflammatory properties as a Janus kinase inhibitor to prevent pCIA while benefitting from the hair growth promoting activity of chitosan. Baricitinib loaded chitosan nanoparticles were prepared using various cosolvents and their physicochemical properties were evaluated (particle size, zeta potential and entrapment efficiency). The optimized formulation, F4-Bar, prepared with PEG 400 as a cosolvent, exhibited a particle size of 247 ± 10.5 nm, a PDI of 0.427 ± 0.04, a zeta potential of +25.8 ± 0.21 mV and a high entrapment efficiency of 67.3 ± 1.8%. Fourier-transform infrared spectroscopy (FTIR) confirmed the successful encapsulation of baricitinib within the nanoparticles matrix and TEM imaging was used to investigate the morphology of the nanoparticles and confirm their particle size. Skin permeation and deposition studies using Confocal Raman Spectroscopy and Franz diffusion cells demonstrated the superior performance of F4-Bar compared to free baricitinib solution. The nanoparticles showed negligible systemic permeation while achieving a nearly fourfold increase in baricitinib deposition in the stratum corneum and more importantly the dermis layer, the target site for hair follicles, suggesting potential effective follicular targeting. Testing the therapeutic efficiency in chemotherapy induced alopecia in C57BL/6 mice in vivo revealed a potent anti-inflammatory effect and hair growth promoting activity of the formula. The study successfully demonstrates that cosolvent optimized chitosan nanoparticles can effectively encapsulate baricitinib, enhance its dermal deposition offering a novel synergistic approach for protection against CIA.