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

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.