Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Biomacromolecules. 2010 Oct 11;11(10):2610-20. doi: 10.1021/bm100561v.
The objective of this study was to design lipopolymers for hydrophobic drug delivery. Poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol) (PEG-PCD) lipopolymers were synthesized and characterized by (1)H NMR, FT-IR, GPC, and DSC. The critical micelle concentration (CMC) of PEG-PCD micelles was around 10(-8) M and decreased with increasing length of hydrophobic block. PEG-PCD micelles could efficiently load a model drug embelin into its hydrophobic core and significantly improve its solubility. The loading capacity was dependent on the polymer core structure, but the length of hydrophobic core had little effect. PEG-PCD formed both spherical and cylindrical micelles, which were dependent on the copolymer structure and composition. PEG-PCD lipopolymers with various hydrophobic core lengths showed similar drug release profiles, which were slower than that of poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) (PEG-PBC) micelles. Embelin loaded PEG-PCD micelles showed significant inhibition of C4-2 prostate cancer cell proliferation, while no obvious cellular toxicity was observed for blank micelles.
本研究旨在设计用于疏水性药物递送的脂质体。聚乙二醇-嵌段-聚（2-甲基-2-羧基-碳酸丙烯酯-接枝-十二醇）（PEG-PCD）脂质体通过（1）H NMR、FT-IR、GPC 和 DSC 进行了合成和表征。PEG-PCD 胶束的临界胶束浓度（CMC）约为 10（-8）M，且随着疏水性嵌段长度的增加而降低。PEG-PCD 胶束可以有效地将模型药物 Embelin 装载到其疏水性核心中，并显著提高其溶解度。载药量取决于聚合物核结构，但疏水性核的长度影响较小。PEG-PCD 形成了球形和圆柱形胶束，这取决于共聚物的结构和组成。具有不同疏水性核长度的 PEG-PCD 脂质体表现出相似的药物释放曲线，其释放速度比聚乙二醇-嵌段-聚（2-甲基-2-苯甲氧基羰基-碳酸丙烯酯）（PEG-PBC）胶束慢。负载 Embelin 的 PEG-PCD 胶束对 C4-2 前列腺癌细胞增殖具有显著的抑制作用，而空白胶束则没有明显的细胞毒性。
