Optimization, In vitro and In vivo Evaluation of an Azithromycin Nanosuspension-Based Nanogel for Enhanced Dermal Delivery.

Abstract

Introduction/objective: Azithromycin is a BCS class II macrolide antibiotic characterized by poor aqueous solubility, a limited dissolution rate, and relatively low oral bioavailability (37%), limiting its therapeutic effectiveness for the treatment of skin infections. This study aimed to design and optimize an azithromycin nanosuspension-based nanogel using a Box-Behnken design.

Methods: Azithromycin nanosuspension was prepared by the antisolvent precipitation method followed by probe sonication. The effects of formulation-variable concentrations on particle size, polydispersity index, and zeta potential were optimized using a Box-Behnken design. The optimized formulation was incorporated into a Carbopol-based gel and subsequently evaluated. In vitro release, ex vivo skin permeation, in vivo dermal irritation, antimicrobial activity, and stability studies were performed.

Results: The optimized formulation contained PVP K30 (0.1% w/v), Tween 80 (0.2% w/v), and HPMC E5 (0.02% w/v), yielding a particle size of 30.65 ± 1.7 nm, polydispersity index of 0.13 ± 0.01, and zeta potential of -0.53 ± 0.13 mV. The nanogel significantly enhanced ex vivo permeation across rat skin (flux 16.8 ± 0.45 μg/cm²·min) compared with the plain hydroalcoholic gel (6.0 ± 0.2 μg/cm²·min). The optimized nanogel exhibited appreciable dermal safety and enhanced antibacterial efficacy against Staphylococcus aureus and Escherichia coli.

Discussion: The improved performance of the selected nanogel was attributed to the nanosuspended particles, which enhanced azithromycin dissolution, localization at the application site, and permeation across the dermal layers.

Conclusion: The optimized nanogel exhibited enhanced dissolution, controlled drug release, improved skin permeation, local antimicrobial efficacy, and good dermal tolerability.