Itraconazole-Loaded Polycaprolactone Nanoparticle Gel for Enhanced Transdermal Delivery: Development,...

Itraconazole (ITZ) is a BCS class II antifungal agent difficult to formulate due to its poor water solubility (<0.2 mmol /mL) and variable oral bioavailability (~55%). This study aimed to develop Polycaprolactone (PCL) nanoparticles to improve their transdermal delivery.

The nanoparticles were prepared using a modified nanoprecipitation method, resulting in ten formulations (F1 to F10). The optimized formulation (F2) was incorporated into a carbopol gel. Characterization included particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), and in vitro drug release at pH 5.5 and 7.4. Ex vivo permeation, skin irritation, and stability were also evaluated.

Formulation F2 (40 mg PCL, 2% Poloxamer 407 showed optimal properties: particle size of 154.6 nm, PDI (0.378), zeta potential (-10.7 ± 5.36 mV), and EE (88.4 ± 1.2%). A pH-dependent sustained release was observed, with 80.41% and 94.34% cumulative release at pH 5.5 and 7.4 over 24 hours, respectively, following Higuchi kinetics (R²= 0.9804 at pH 5.5). The gel demonstrated significantly higher permeation (Q_{2 4}: 173.29 ± 3.12 μg/cm²; Jss: 7.22 ± 0.15 μg/cm²/h) versus plain gel (Q_{2 4}: 75.35 ± 1.35 μg/cm²; Jss: 3.11 ± 0.08 μg/cm²/h), with an enhancement ratio of 2.32. Characterization confirmed the amorphous state of ITZ and absence of interactions. The formulation was non-irritating (PII=0) and stable for three months.

A promising and biocompatible PCL-based gel was successfully developed, providing an effective approach for enhanced transdermal delivery of ITZ through sustained drug release and improved skin permeability.