Invasomes and Nanostructured Lipid Carriers for Targeted Delivery of Ceftazidime Combined with N-Acetylcysteine: A Novel Approach to Treat Pseudomonas aeruginosa-Induced Keratitis.

Abstract

Objectives: This study was designed to optimize a ceftazidime (CTZ)-loaded nanocarrier that could efficiently permeate across corneal tissues. Moreover, N-acetylcysteine (NAC) was combined with an optimized CTZ-loaded formula to augment the antimicrobial activity and facilitate the efficient healing of Pseudomonas aeruginosa-induced keratitis. Methods: Different CTZ-loaded invasomes (INVs) and CTZ-loaded nanostructured lipid carriers (NLC) were fabricated and fully characterized via the determination of the entrapment efficiency (EE%), particle size (PS), surface charge, and percentage of CTZ release. Next, NAC was added to the optimized formulae from each nanocarrier, which were further assessed through ex vivo corneal permeation and in vitro antimicrobial activity studies. Finally, an in vivo evaluation of the optimal nanocarrier in the presence of NAC was performed. Results: Both nanocarriers showed nanoscale PS with sufficient surface charges. CTZ-loaded NLC formulae showed a higher EE% range with a sustained drug release profile. Both optimized formulae showed a spherical shape and excellent stability. Moreover, the antibacterial activity and biofilm inhibition assessments confirmed the synergistic effects of NAC when combined with different CTZ-loaded nanocarriers. However, the optimized CTZ-loaded INV formula achieved higher corneal permeation and deposition compared to the optimized CTZ-loaded NLC formula. Finally, the in vivo assessment confirmed the dominance of the optimized CTZ-loaded INV formula combined with NAC, where the microbiological, histopathological, and immunohistopathological examinations showed the rapid eradication of keratitis. Conclusions: Recent strategies for the incorporation of antibiotics into nanocarriers, combined with mucolytic agents, can offer a promising platform to boost the therapeutic efficiency of antibiotics and prevent antimicrobial resistance.