Effect of polymer amphiphilicity on loading of a therapeutic enzyme onto protective fulamentous and spherical polymer nanocarrlers
Effect of polymer amphiphilicity on loading of a therapeutic enzyme onto protective fulamentous and spherical polymer nanocarrlers
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DOI：
10.1021/bm700888h
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发表时间：
2007-12-01
影响因子：
6.2
通讯作者：
Muzykantov, Vladimir R.
中科院分区：
文献类型：
--
作者：
Simone, Eric A.;Dziubla, Thomas D.;Muzykantov, Vladimir R.
快速清除和蛋白质分解限制了蛋白质疗法的传递和疗效。负载到可生物降解的聚合物纳米载体(PNC)可能会保护蛋白质，延长治疗时间，但负载可能会因蛋白质的展开和失活而变得复杂。我们用冻融复乳将活性酶包埋在甲氧基聚乙二醇单嵌段乳酸(mpeg-pla)PNC中(J.Control Release 2005,102(2)，427-439)。基于两亲性自组装的概念，我们假设控制自发曲率的共聚物嵌段比例会影响PNC的形态和负载。我们考察了PNC的产量、形态、稳定性、载药量、活性和抗氧化酶过氧化氢酶的抗性。随着疏水聚合物含量的增加，PNC从球形转变为丝状，这与低分子量两亲分子自组装的趋势一致。重要的是，一种两嵌段共聚物形成了丝状颗粒，负载了大量的蛋白酶抗性酶，首次证明了活性治疗酶被封装到丝状载体中。PNC的形态也极大地影响了其降解，提供了一种新的控制释放手段。
Rapid clearance and proteolysis limit delivery and efficacy of protein therapeutics. Loading into biodegradable polymer nanocarriers (PNC) might protect proteins, extending therapeutic duration, but loading can be complicated by protein unfolding and inactivation. We encapsulated active enzymes into methoxy-poly(ethylene glycol-block-lactic acid) (mPEG-PLA) PNC with a freeze-thaw double emulsion (J. Controlled Release 2005, 102 (2), 427-439). On the basis of concepts of amphiphile self-assembly, we hypothesized that the copolymer block ratio that controls spontaneous curvature would influence PNC morphology and loading. We examined PNC yield, shape, stability, loading, activity, and protease resistance of the antioxidant enzyme, catalase. PNC transitioned from spherical to filamentous shapes with increasing hydrophobic polymer fraction, consistent with trends for self-assembly of lower MW amphiphiles. Importantly, one diblock copolymer formed filamentous particles loaded with significant levels of protease-resistant enzyme, demonstrating for the first time encapsulation of an active therapeutic enzyme into filamentous carriers. PNC morphology also greatly influenced its degradation, offering a new means of controlled delivery.