Experimental and Clinical Research Center, Kocaeli University, Turkey; Graduate School of Natural and Applied Sciences, Department of Biomedical Engineering, Kocaeli University, Turkey.
Department of Medical Microbiology, Kocaeli University Medical Faculty, Turkey.
Int J Pharm. 2019 Oct 5;569:118578. doi: 10.1016/j.ijpharm.2019.118578. Epub 2019 Jul 27.
Chitosan (CS), due to its inherent mucoadhesive property and biofilm penetration ability, can be considered as very potent vehicle for local drug delivery to the lungs. This study reports on the preparation and in vitro antibacterial activity and cytotoxicity determination of ciprofloxacin loaded chitosan (Cipro-CS) microparticles with size in the range of 0.1-1 µm, which may provide advantages of lower nanotoxicity and lower local clearance. Cipro-CS microparticles were prepared by ionic gelation method and their size, zeta potential and drug release pattern determined. The antibacterial activities of CS and Cipro-CS microparticles against pneumonia causing agents, namely Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, were evaluated by determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The biocompatibility of the microparticles was tested in the human lung epithelial cell (BEAS-2B) culture, and microparticle association with the bacteria and epithelial cells was evaluated by transmission electron microscopy. Only the Cipro-CS microparticles, but not the CS microparticles, inhibited bacterial growth at concentrations not significantly cytotoxic to BEAS-2B cells. The Cipro-CS microparticles were able to damage the cell wall and membrane of the bacteria, and the ones ≤200 nm in size were internalized by both the BEAS-2B cells and the microorganisms.
壳聚糖（CS）由于其固有的黏膜黏附特性和生物膜穿透能力，可被视为向肺部局部递送药物的非常有效的载体。本研究报告了载有环丙沙星的壳聚糖（Cipro-CS）微球的制备及其体外抗菌活性和细胞毒性的测定，其粒径在 0.1-1μm 范围内，可能具有较低纳米毒性和较低局部清除率的优势。采用离子凝胶法制备 Cipro-CS 微球，并测定其粒径、Zeta 电位和药物释放模式。通过测定最小抑菌浓度（MIC）和最小杀菌浓度（MBC），评估 CS 和 Cipro-CS 微球对引起肺炎的病原体（大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌）的抗菌活性。通过人肺上皮细胞（BEAS-2B）培养测试微球的生物相容性，并通过透射电子显微镜评估微球与细菌和上皮细胞的结合情况。只有 Cipro-CS 微球而不是 CS 微球在对 BEAS-2B 细胞无明显细胞毒性的浓度下抑制细菌生长。Cipro-CS 微球能够破坏细菌的细胞壁和膜，并且粒径≤200nm 的微球被 BEAS-2B 细胞和微生物内化。
