National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China; Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, China; School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510641, China.
School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China; Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, China.
Int J Pharm. 2014 Apr 10;464(1-2):225-33. doi: 10.1016/j.ijpharm.2013.12.047. Epub 2014 Jan 22.
Di-block polymer of poly (lactic-co-glycolic acid)-poly (ethylene glycol) (PLGA-PEG) end-capped with capecitabine (CAP) at the hydrophobic domain and folate (FA) at hydrophilic domain were synthesized respectively. The products were extensively studied by nuclear magnetic resonance ((1)H NMR) and gel permeation chromatography (GPC) measurement. By using emulsion-solvent evaporation method, the two conjugates, drug CAP and tetramethoxysilane (TMOS) were mixed to form the CAP entrapped nanoparticles (NPs) with the FA moieties exposed on NPs surface, while simultaneously forming a cross-linked silica shell out of hydrophobic PLGA core domain. The testing results showed the CAP-loaded NPs presented suitable physical stability, favorable size around 200 nm, negative zeta potential charge (-28.43 ± 2.55 mV) and high encapsulation efficiency (69%). Both silica shell cross-linked drug-loaded NPs (SSCL NPs) and none silica shell cross-linked NPs (NSSCL NPs) provided an initial burst release and followed by a sustained two-stage release of the CAP. Straight lines approximate the steady-state for the two-stage release, and the K/K' of the two stages are 1.96304 and 1.78697 respectively suggesting the silica shell influenced the release of first stage significantly.
分别合成了以喜树碱（CAP）封端于疏水区、叶酸（FA）封端于亲水区的聚（乳酸-共-乙醇酸）-聚（乙二醇）二嵌段聚合物（PLGA-PEG）。通过核磁共振（1H NMR）和凝胶渗透色谱（GPC）测量对产物进行了广泛研究。通过乳液溶剂蒸发法，将两种缀合物，药物 CAP 和四甲氧基硅烷（TMOS）混合，在 NPs 表面暴露 FA 部分的同时，形成 CAP 包封的纳米颗粒（NPs），而同时形成疏水性 PLGA 核域外的交联硅壳。测试结果表明，载有 CAP 的 NPs 具有合适的物理稳定性、约 200nm 的理想尺寸、负的 ζ 电位（-28.43±2.55mV）和高包封效率（69%）。交联载药硅壳纳米颗粒（SSCL NPs）和非交联载药纳米颗粒（NSSCL NPs）都提供了初始突释，随后是 CAP 的持续两阶段释放。两条直线近似于两阶段释放的稳态，两个阶段的 K/K'分别为 1.96304 和 1.78697，表明硅壳显著影响了第一阶段的释放。
