Design and optimization of mucoadhesive PCL/chitosan nanoparticles for vaginal delivery of miconazole

Abstract

The development of effective vaginal drug delivery systems remains challenging due to physiological barriers such as mucus turnover, pH variability, and limited drug residence time. In this study, mucoadhesive polymeric nanoparticles based on poly[ε-caprolactone] [PCL] and chitosan were designed and optimized for vaginal delivery of miconazole using a multivariable experimental approach. Nanoparticles were prepared by the solvent emulsification–diffusion method, and the influence of formulation variables [PCL, miconazole, and chitosan concentrations] on physicochemical properties was evaluated using response surface methodology [RSM] and a quadratic model. Statistical analysis [ANOVA] indicated that particle size and zeta potential were well described by the model [r² ≈ 0.82], while polydispersity index and encapsulation efficiency showed lower dependence on formulation variables. Particle size ranged from 207 to 321 nm with low PdI [<0.3], indicating homogeneous nanosystems. Zeta potential varied from −1.7 to +33.5 mV, with chitosan significantly influencing surface charge and mucoadhesive ability. Encapsulation efficiency ranged from 72% to 85%. Optimization using a desirability function [D ≈ 0.86] yielded nanoparticles with ~195 nm size, ~0.12 PdI, ~+5 mV zeta potential, and ~80% encapsulation efficiency. The agreement between predicted and experimental values confirmed model reliability, supporting the rational design of mucoadhesive nanosystems for vaginal drug delivery.