Formulation Development and Characterization of Posaconazole Loaded Nanoparticle Gel

Abstract

The present study focused on the development and evaluation of Posaconazole-loaded nanostructured lipid carriers (NLCs) as a novel topical delivery system to overcome limitations of conventional formulations such as poor solubility, low bioavailability, and inadequate tissue retention. Posaconazole, a broad-spectrum triazole antifungal, was incorporated into solid lipid nanoparticles (SLNs) and NLCs using the melt emulsification ultrasonication method, with optimization carried out through a full factorial design (3³). Critical formulation factors including lipid-drug ratio, surfactant concentration, and sonication time significantly influenced particle size and entrapment efficiency. Optimized formulations demonstrated particle sizes ranging from 80–150 nm for NLCs with high entrapment efficiency (up to 85%) and stable zeta potential (–13 to –15 mV). Differential Scanning Calorimetry and Scanning Electron Microscopy confirmed successful drug encapsulation and uniform spherical nanoparticles, respectively. The optimized NLC was incorporated into an aloevera based carbopol gel, yielding a formulation with appropriate pH, viscosity, spreadability, and rheological characteristics suitable for topical application. In vitro permeation studies indicated enhanced skin retention of Posaconazole with minimal systemic penetration, while fluorescent microscopy confirmed deeper layer skin targeting. Antifungal evaluations demonstrated superior efficacy of the NLC gel against Candida albicans and Aspergillus fumigatus, with sustained activity, reduced fungal burden, and significant anti-inflammatory effects in in vivo models. Overall, the developed Posaconazole-loaded NLC gel showed promising potential as a safe and effective topical drug delivery system, combining enhanced local drug retention with improved therapeutic outcomes and reduced systemic side effects.