School of Pharmaceutical Science, Shandong University, Ji'nan 250012, China.
School of Pharmaceutical Science, Shandong University, Ji'nan 250012, China.
Colloids Surf B Biointerfaces. 2015 Jul 1;131:191-201. doi: 10.1016/j.colsurfb.2015.04.057. Epub 2015 May 5.
Drug loading is a key procedure in the preparation of drug-loaded nano-carriers. In this study, the paclitaxel (PTX)-loaded polymeric complex micelles (FA-P123-PTX/PTX micelles) with double drug-loading strategies were designed and prepared to improve the drug loading percentage of carriers and its anti-tumor efficiency. PTX was simultaneously conjugated to pluronic P123 (P123) polymer and encapsulated inside the P123 complex micelle. Folate (FA) was linked to the surface of micelles for the active target delivery of micelles to tumor cells. The FA-P123-PTX/PTX micelles showed spherical shaped with high drug loading of 18.08±0.64%. The results of cellular uptake studies suggested that FA could promote the internalization of micelles into the FR positive cells. FA-P123-PTX/PTX micelles showed significant higher anti-tumor activity against FR positive tumor cells compared to Taxol(®) (p<0.05). Moreover, the FA-P123-PTX/PTX micelles exhibited higher anti-tumor efficacy in B16 bearing mice with better safety property compared with Taxol(®). These results suggested that FA-P123-PTX/PTX micelles with double drug-loading strategies showed great potential for targeted delivery of anti-cancer drugs.
载药是制备载药纳米载体的关键步骤。在这项研究中，设计并制备了具有双重载药策略的紫杉醇（PTX）载药聚合物复合胶束（FA-P123-PTX/PTX 胶束），以提高载体的载药百分比及其抗肿瘤效率。PTX 同时与普朗尼克 P123（P123）聚合物缀合并包裹在 P123 复合胶束内。叶酸（FA）连接到胶束表面，以实现胶束对肿瘤细胞的主动靶向递送。FA-P123-PTX/PTX 胶束呈球形，载药量高达 18.08±0.64%。细胞摄取研究结果表明，FA 可促进胶束进入 FR 阳性细胞的内化。与 Taxol(®)（p<0.05）相比，FA-P123-PTX/PTX 胶束对 FR 阳性肿瘤细胞表现出显著更高的抗肿瘤活性。此外，与 Taxol(®)相比，FA-P123-PTX/PTX 胶束在携带 B16 的小鼠中表现出更高的抗肿瘤疗效和更好的安全性。这些结果表明，具有双重载药策略的 FA-P123-PTX/PTX 胶束具有作为抗癌药物靶向递送的巨大潜力。
