Preparation and Evaluation of Vancomycin-Loaded N-trimethyl Chitosan Nanoparticles
Preparation and Evaluation of Vancomycin-Loaded N-trimethyl Chitosan Nanoparticles
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DOI：
10.3390/polym7091488
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发表时间：
2015-09
期刊：
影响因子：
5
通讯作者：
Jiaojiao Xu;Beihua Xu;D. Shou;X. Xia;Ying Hu
中科院分区：
文献类型：
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作者：
Jiaojiao Xu;Beihua Xu;D. Shou;X. Xia;Ying Hu
由耐药病原体引起的慢性细胞内感染对慢性骨髓炎的治疗提出了挑战。这种治疗需要细胞内递送系统来持续释放抗生素，如万古霉素（VCM），这是一种用于治疗许多临床耐药细菌的最后手段。在这项工作中，我们报道了负载vcm的n -三甲基壳聚糖（TMC）纳米颗粒及其在药物递送方面的潜在应用。结果表明：制备的纳米颗粒以球形为主，平均粒径为220 nm， zeta电位为正，负载效率为73.65%±1.83%。此外，它们的药物释放谱符合Higuchi缓释模型，具有非菲克扩散。在24 h的时间内，优化的纳米颗粒内的药物释放量为6.51%±0.58%。体外细胞学研究表明，暴露于TMC纳米颗粒材料后，成骨细胞（OBs）表现出更高的碱性磷酸酶活性（ALP）。此外，TMC纳米颗粒增加了OB对水溶性量子点（QDs）的吸收，纳米颗粒和VCM/TMC混合物均提高了OB的增殖活性。研究了纳米颗粒的最小抑菌浓度（MIC, 60 μg/mL）、半最大抑菌浓度（IC50, 48.47 μg/mL）、抑菌带直径（DIZ, 1.050 cm）和比浊法（TB）测定。结果表明，VCM/TMC纳米颗粒对革兰氏阳性菌金黄色葡萄球菌具有良好的抗菌活性。这些发现表明，vcm负载的TMC纳米颗粒具有良好的潜力，可以持续向骨感染递送抗生素。
Chronic intracellular infections caused by drug-resistant pathogens pose a challenge to the treatment of chronic osteomyelitis. Such treatment requires an intracellular delivery system for the sustained release of antibiotics such as vancomycin (VCM), which is an antibiotic of last resort used against many clinically resistant bacteria. In this work, we report VCM-loaded N-trimethyl chitosan (TMC) nanoparticles and their potential application for drug delivery. The results showed that the prepared nanoparticles were predominantly spherical in shape with an average particle diameter of 220 nm, a positive zeta potential, and a loading efficiency of 73.65% ± 1.83%. Furthermore, their drug release profile followed the Higuchi model for sustained release, with non-Fickian diffusion. Over a 24-h period, 6.51% ± 0.58% of the drug within the optimized nanoparticles was released. In vitro cytology showed that osteoblasts (OBs) exhibited higher alkaline phosphatase activity (ALP) after exposure to TMC nanoparticle material. Furthermore, TMC nanoparticles increased the uptake of water-soluble quantum dots (QDs) by OBs, and both nanoparticles and VCM/TMC mixtures improved OB proliferative activity. We also investigated the minimum inhibitory concentration (MIC, 60 μg/mL), half maximal inhibitory concentration (IC50, 48.47 μg/mL), diameter of inhibition zone (DIZ, 1.050 cm), and turbidimetric (TB) assay of nanoparticles. All data demonstrated that VCM/TMC nanoparticles had excellent antibacterial activity against the Gram-positive bacterium Staphylococcus aureus. These findings suggest that VCM-loaded TMC nanoparticles have good potential for the sustained delivery of antibiotics to bone infections.