Study on Construction of and Pharmacodynamics of Baicalin-Minoxidil Co-Loaded Nanogel

Androgenetic alopecia (AGA) is a chronic and highly prevalent hair loss disorder for which current topical therapies are limited by undesirable side effects, dose-dependent efficacy, and poor skin penetration. Objective: Here, we developed a baicalin-minoxidil co-loaded nanogel (Bai-Min-NGs) to synergistically enhance transdermal drug delivery and promote hair regeneration. Methods: The optimized nanogel exhibited favorable colloidal attributes, featuring a nanoscale hydrodynamic diameter of 156 ± 3.62 nm, narrow size distribution (polydispersity index of 0.144 ± 0.011), surface zeta potential of −26.1 ± 0.37 mV, high encapsulation efficiencies (95.86 ± 1.34% for baicalin and 82.16 ± 2.50% for minoxidil), and satisfactory drug loading capacities (1.92 ± 0.08% and 1.64 ± 0.06%, respectively). Results: Enhanced cellular internalization through endocytosis further promoted the proliferation and migration of human dermal papilla cells, demonstrating a synergistic biological effect beyond either drug alone. In an androgenetic alopecia mouse model, topical Bai-Min-NGs significantly accelerated hair regrowth, as evidenced by increased hair length, hair weight, hair follicle density, and dermal thickness. Notably, the nanogel achieved superior therapeutic efficacy while maintaining excellent local and systemic biosafety. Mechanistically, Bai-Min-NGs activated the Wnt/β-catenin signaling pathway by upregulating Wnt7b and Wnt10b expression, suppressing TGF-β1, and increasing the protein expression of GSK3β, phosphorylated GSK3β, β-catenin, and VEGF, thereby promoting hair follicle regeneration and angiogenesis. Conclusions: Collectively, Bai-Min-NGs provide a promising topical co-delivery nanoplatform integrating superior cutaneous retention with endogenous pathway activation for hair regeneration therapy.