Chitosan Nanoparticles for Topical Drug Delivery in Chemotherapy-Induced Alopecia: A Comparative Study of Five Repurposed Pharmacological Agents.

Background/

Objectives

Chemotherapy-induced alopecia is a common and distressing side effect of cancer treatment, significantly impacting patients' psychological well-being. Nanocarriers offer a promising strategy for targeted drug delivery to hair follicles, while chitosan nanoparticles have demonstrated hair-growth-promoting properties. This study explores the potential of chitosan nanoparticles as a topical delivery system for five pharmacological agents-phenobarbital, pioglitazone, rifampicin, N-acetylcysteine, and tacrolimus-to prevent chemotherapy-induced alopecia.

Methods

Drug-loaded chitosan nanoparticles were prepared using the ionic gelation technique and characterized by particle size, zeta potential, entrapment efficiency, FT-IR spectroscopy, and TEM imaging. Their efficacy was assessed in a cyclophosphamide-induced alopecia model in C57BL/6 mice through macroscopic observation, histopathological examination, and scanning electron microscopy of regrown hair.

Results

The prepared particles were spherical, cationic, and between 205 and 536 nm in size. The entrapment efficiencies ranged from 8% to 63%. All five drugs mitigated follicular dystrophy, shifting the hair follicle response from dystrophic catagen to dystrophic anagen. Phenobarbital demonstrated the most significant hair regrowth and quality improvements, followed by N-acetyl cysteine and pioglitazone. Tacrolimus showed moderate efficacy, while rifampicin was the least effective.

Conclusions

These findings suggest that phenobarbital-loaded chitosan nanoparticles represent a promising approach for the prevention and treatment of chemotherapy-induced alopecia, warranting further investigation for clinical applications.