<p>Hair loss is a prevalent dermatological disorder that significantly affects quality of life. Among FDA approved treatments, topically applied minoxidil is commonly used. Nevertheless, its low water solubility necessitates use of irritating solvents which hinder its clinical administration. Since these solvents usually cause adverse reactions, nanotechnology-based carriers have emerged as promising strategies for topical delivery of minoxidil. Thus, we prepared topical delivery nanocarriers, i.e., chitosan-coated nanocapsules (ChiNCs), to increase percutaneous delivery through intrinsic characteristics of chitosan and to increase encapsulation of minoxidil into the nanocarriers. ChiNCs were prepared through simple nanoprecipitation and encapsulated in high amounts of minoxidil. The minoxidil-loaded ChiNCs (MXD@ChiNCs) were evaluated for their physicochemical characteristics, colloidal stability, release profile, skin penetration, cytotoxicity, proliferation, hair growth via animal, and histological analyses. MXD@ChiNCs were successfully loaded with 50 wt.% of MXD and maintained good stability. Additionally, release profile of MXD from MXD@ChiNCs exhibited sustained release behavior and improved skin penetration. Particularly, ChiNCs showed no cytotoxicity in skin-related cell lines and did not influence cell proliferation. MXD@ChiNCs demonstrated dose-dependent therapeutic efficacy and considerably boosted hair regrowth compared to other MXD formulations, as evidenced by macroscopic and histological results. These observations highlight potential of MXD@ChiNCs as topical delivery system for alopecia.&#xa0;</p> Graphical abstract <p>MXD@ChiNCs enhance minoxidil penetration and stimulate hair regeneration via microenvironmental remodeling.</p> <p></p>