Josef Mina, Abdellatif Menna M, Abdelmonem Rehab, El-Nabarawi Mohamed A, Teaima Mahmoud, Bedair Hadeer M, Attia Alshaimaa
Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, P.O. Box 77, Giza 12566, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, El-Kasr El-Aini Street, Cairo 11562, Egypt.
Pharmaceutics. 2025 Sep 11;17(9):1184. doi: 10.3390/pharmaceutics17091184.
: 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 -induced keratitis. : 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. : 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. : 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.
本研究旨在优化一种负载头孢他啶（CTZ）的纳米载体，使其能够有效穿透角膜组织。此外，将N - 乙酰半胱氨酸（NAC）与优化后的负载CTZ配方相结合，以增强抗菌活性并促进诱导性角膜炎的有效愈合。：制备了不同的负载CTZ的泡囊（INVs）和负载CTZ的纳米结构脂质载体（NLC），并通过测定包封率（EE%）、粒径（PS）、表面电荷和CTZ释放百分比进行了全面表征。接下来，将NAC添加到每种纳米载体的优化配方中，并通过离体角膜渗透和体外抗菌活性研究进行进一步评估。最后，对存在NAC的最佳纳米载体进行了体内评估。：两种纳米载体均显示出具有足够表面电荷的纳米级PS。负载CTZ的NLC配方显示出更高的EE%范围和持续的药物释放曲线。两种优化配方均呈球形且稳定性极佳。此外，抗菌活性和生物膜抑制评估证实了NAC与不同负载CTZ的纳米载体联合使用时的协同作用。然而，与优化后的负载CTZ的NLC配方相比，优化后的负载CTZ的INV配方实现了更高的角膜渗透和沉积。最后，体内评估证实了优化后的负载CTZ的INV配方与NAC联合使用的优势，其中微生物学、组织病理学和免疫组织病理学检查显示角膜炎迅速消除。：最近将抗生素纳入纳米载体并与粘液溶解剂相结合的策略，可以提供一个有前景的平台，以提高抗生素的治疗效率并防止抗菌耐药性。
