Self-assembly of pH-responsive biodegradable mixed micelles based on anionic and cationic polycarbonates for doxorubicin delivery.
Self-assembly of pH-responsive biodegradable mixed micelles based on anionic and cationic polycarbonates for doxorubicin delivery.
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DOI：
10.1016/j.colsurfb.2016.05.029
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发表时间：
2016-09
期刊：
影响因子：
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通讯作者：
Lin Yu;Chengyu Lin;Zhen Zheng;Z. Li;Xinling Wang
中科院分区：
文献类型：
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作者：
Lin Yu;Chengyu Lin;Zhen Zheng;Z. Li;Xinling Wang
制备了聚（5-丙基-1，3-二氧六环-2-酮）-b-二甲胺改性聚碳酸酯（PC（MPpC-MMA））和聚乙二醇-b-羧基化聚碳酸酯（PEG-PCCOOH）两嵌段共聚物，构建了pH响应、高稳定性、可生物降解的混合胶束。两种共聚物在pH 7.4的PBS中通过静电和疏水相互作用自组装成混合胶束。以具有疏水内核的聚碳酸酯（MPpC-MMA）为载药载体，二甲胺部分为引发剂，对混合胶束进行了拆分。PEG-PCCOOH可以屏蔽胶束对正常组织可能显示的不利作用。另外，游离羧基的存在可以进一步提高正电荷药物的负载效率。随着PEG-PCCOOH与PC（MPpC-MMA）摩尔比的增加，胶束的粒径和zeta电位逐渐减小。这些混合胶束可以承受高离子强度的等离子体，并且在长时间储存中相当稳定。然而，通过将pH值从7.4降低到5.0，它们可以解离成直径为20 nm的更小的纳米颗粒，并显示出正表面性质。体外释药研究表明，在pH 5.0比在pH 7.4更快的释放速率。MTT法显示出对HepG 2细胞的有效细胞毒活性。这些结果表明，新型共混聚碳酸酯胶束在生物医学领域具有巨大的应用潜力。
Poly(5-propyl-1,3-dioxan-2-one)-b-dimethylamine modified polycarbonate (PC(MPpC-MMA)) and poly(ethylene glycol)-b-carboxylated polycarbonate (PEG-PCCOOH) diblock copolymers were prepared to construct a pH responsive, highly stable and biodegradable mixed micelle. The two copolymers self-assembled into the mixed micelle in pH 7.4 PBS driven by electrostatic and hydrophobic interactions. PC(MPpC-MMA) with hydrophobic inner core was used for carrying drug and the dimethylamine part was designed as a trigger to disassemble the mixed micelle. PEG-PCCOOH could shield the positive character of the micelle which might show disadvantage to normal tissue. In addition, the free carboxyl groups could further increase the loading efficiency of positive charged drugs. The size and zeta potential of the micelle gradually decreased with increasing the molar ratio of PEG-PCCOOH to PC(MPpC-MMA). These mixed micelles could withstand high ionic strength of plasma and were rather stable for long time storage. However, via decrease of pH value from 7.4 to 5.0, they could undergo dissociation into smaller nanoparticles which were in a diameter of 20 nm and showed positive surface nature. In vitro drug delivery studies showed a faster release rate at pH 5.0 than that at pH 7.4. The MTT assays demonstrated potent cytotoxic activity against HepG2 cells. All these results indicate that the newly mixed polycarbonate micelle can show great potential in biomedical field.