College of Marine Life Science, Ocean University of China, Qingdao 266003, PR China.
Colloids Surf B Biointerfaces. 2013 Mar 1;103:345-53. doi: 10.1016/j.colsurfb.2012.11.012. Epub 2012 Nov 29.
Oleoyl-carboxymethyl-chitosan (OCMCS) was synthesized and were soluble at neutral pH. The critical micelle concentration (CMC) of OCMCS in deionized water was 0.021 mg/ml. OCMCS nanoparticles were successfully prepared via self-assembly with mean diameter of 215.34 nm, zeta potential of 19.26 mV and an almost spherical shape as determined by electron microscopy. The OCMCS nanoparticles showed low erythrocyte membrane-damaging effect. The MTT survival assay indicated no significant cytotoxicity to Caco-2 cells and MEFs cells. The uptake of FITC labeled OCMCS nanoparticles by Caco-2 cells was confirmed via confocal laser scanning microscope (CLSM). In vivo toxicity assays were performed via histopathological evaluation, and no specific anatomical pathological changes or tissue damage was observed in the tissues of carps. The extent of tissue distribution and retention following oral administration of FITC-OCMCS nanoparticles was analyzed for 3 days. After 3 days, the nanoparticles remained detectable in the muscle, heart, kidney, liver, intestine, and spleen. The results showed that 34.32% of the particles were localized in the liver, 18.79% in the kidney, and 17.36% in the heart. The lowest percentage was observed in the muscle. These results implied that OCMCS nanoparticles had great potential to be applied as safe carriers for the oral administration of protein drugs.
油酰羧甲基壳聚糖（OCMCS）可在中性 pH 下溶解。其在去离子水中的临界胶束浓度（CMC）为 0.021mg/ml。通过自组装成功制备了平均直径为 215.34nm、Zeta 电位为 19.26mV、呈近球形的 OCMCS 纳米粒子，这可通过电子显微镜确定。OCMCS 纳米粒子对红细胞膜的破坏作用较小。MTT 存活试验表明，其对 Caco-2 细胞和 MEFs 细胞无明显细胞毒性。通过共聚焦激光扫描显微镜（CLSM）证实了 FITC 标记的 OCMCS 纳米粒子被 Caco-2 细胞摄取。通过组织病理学评估进行体内毒性试验，在鲤鱼组织中未观察到特定的解剖病理变化或组织损伤。分析了口服 FITC-OCMCS 纳米粒子 3 天后的组织分布和保留程度。3 天后，纳米粒子仍可在肌肉、心脏、肾脏、肝脏、肠和脾脏中检测到。结果表明，34.32%的粒子定位于肝脏，18.79%定位于肾脏，17.36%定位于心脏。在肌肉中观察到的比例最低。这些结果表明，OCMCS 纳米粒子有很大的潜力作为口服给药蛋白质药物的安全载体。
