Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Carbohydr Polym. 2013 Jan 30;92(1):545-54. doi: 10.1016/j.carbpol.2012.08.112. Epub 2012 Sep 6.
In this study, a novel amphiphilic copolymer designed as N-octyl-N-phthalyl-3,6-O-(2-hydroxypropyl) chitosan (OPHPC) were synthesized and then conjugated with folic acid (FA-OPHPC) to produce a targeted drug carrier for tumor-specific drug delivery. OPHPC and FA-OPHPC were characterized by FT-IR, (1)H NMR, (13)C NMR and elemental analysis. Paclitaxel (PTX) loaded OPHPC micelles (PTX-OPHPC) with well-defined spherical shape and homogeneous distribution exhibited drug-loading rate ranging from 33.6% to 45.3% and entrapment efficiency from 50.5% to 82.8%. In the cellular uptake studies, PTX-OPHPC brought about a significantly higher amount of PTX accumulated in human breast adenocarcinoma cell line (MCF-7 cells) compared with Taxol. Moreover, the cellular uptake of PTX in PTX loaded FA-OPHPC micelles (PTX-FA-OPHPC) was 3.2-fold improved in comparison with that of PTX-OPHPC. The results revealed that OPHPC micelle might be a promising drug carrier for promoting PTX cellular uptake and FA-OPHPC micelle could be used as a potential tumor-targeted drug vector.
在这项研究中，设计了一种新型两亲性共聚物 N-辛基-N-邻苯二甲酰基-3,6-O-(2-羟丙基)壳聚糖（OPHPC），然后将其与叶酸（FA-OPHPC）缀合，以产生用于肿瘤特异性药物递送的靶向药物载体。通过傅里叶变换红外光谱（FT-IR）、（1）H NMR、（13）C NMR 和元素分析对 OPHPC 和 FA-OPHPC 进行了表征。具有明确的球形形状和均匀分布的紫杉醇（PTX）负载的 OPHPC 胶束（PTX-OPHPC）的载药率范围为 33.6%至 45.3%，包封效率为 50.5%至 82.8%。在细胞摄取研究中，与 Taxol 相比，PTX-OPHPC 使更多的 PTX 积聚在人乳腺癌腺癌细胞系（MCF-7 细胞）中。此外，与 PTX-OPHPC 相比，负载 PTX 的 FA-OPHPC 胶束（PTX-FA-OPHPC）中的 PTX 细胞摄取增加了 3.2 倍。结果表明，OPHPC 胶束可能是促进 PTX 细胞摄取的有前途的药物载体，FA-OPHPC 胶束可用作潜在的肿瘤靶向药物载体。
