Cationic Corona-Engineered Polymer–Lipid Hybrid Nanoparticles for Enhanced Dermal Penetration and Cellular Bioavailability

-PCL incorporation progressively increased the crystallinity and rigidity of the nanoparticle core, achieving 2-fold reduction in Higuchi release rate constants for sustained curcumin delivery. Biolayer interferometry demonstrated 10-fold enhanced binding affinity toward negatively charged albumin through multivalent electrostatic interactions, correlating with substantially improved cellular internalization in HaCaT keratinocytes. Confocal microscopy of ex vivo porcine skin revealed 70% increased transdermal penetration depth, with maximum fluorescence at 30-40 μm beneath the stratum corneum. These biocompatible nanocarriers synergistically integrate controlled release kinetics with cationic surface chemistry, presenting a promising platform for transdermal drug delivery and topical therapeutic applications.