Abstract
<jats:p>Polymeric nanocapsules based on poly[ε-caprolactone] were developed as a dermal drug delivery system for the controlled administration of neem bioactive compounds. The present study aimed to optimize formulation variables and evaluate their influence on key physicochemical properties including particle size, zeta potential, and encapsulation efficiency. Nanocapsules were prepared using the emulsification–diffusion technique and systematically varied in terms of polymer content, neem extract concentration, collagen functionalization, and polymer/drug ratio. Analysis of variance [ANOVA] revealed that collagen significantly influenced surface charge characteristics, while the polymer/neem ratio was identified as the dominant factor controlling encapsulation efficiency. Particle size was primarily governed by process-related physicochemical parameters rather than individual compositional variables. The optimized nanosystems exhibited submicron particle size distribution, near-neutral surface charge, and high drug loading capacity, suggesting their suitability for follicular targeting and localized dermal delivery. These findings highlight the relevance of formulation balance and surface functionalization in the rational design of polymeric nanocarriers for topical therapeutic applications.</jats:p>