Polymer nanocarriers protecting active enzyme cargo against proteolysis
Polymer nanocarriers protecting active enzyme cargo against proteolysis
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DOI：
10.1016/j.jconrel.2004.10.017
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发表时间：
2005-02-02
影响因子：
10.8
通讯作者：
Muzykantov, VR
中科院分区：
文献类型：
--
作者：
Dziubla, TD;Karim, A;Muzykantov, VR
聚合物纳米载体（PNC），提出作为一个有吸引力的车辆血管药物输送，仍然是一个孤儿技术的酶疗法，由于穷人的负载和失活的蛋白质货物。为了将PNC的酶递送与遏制血管氧化应激的临床相关目标相结合，设计了一种新的冻融包封策略，并将活性大抗氧化酶过氧化氢酶类似于20%的效率负载到由可生物降解的嵌段共聚物聚（乙二醇）-b-聚（乳酸-乙醇酸）组成的PNC（200-300 nm）中。过氧化氢酶的底物H2 O2在PNC聚合物中可自由扩散。此外，负载有PNC的过氧化氢酶在蛋白水解环境中稳定地保持25-30%的H_2O_2降解活性至少18 h，而游离过氧化氢酶在1 h内失去活性。通过PNC纳米技术提供的过氧化氢酶的递送和保护免于溶酶体降解可以提高与血管氧化应激相关的多种疾病状况的治疗有效性和持续时间。(C)2004 Elsevier B. V.保留所有权利。
Polymeric nanocarriers (PNCs), proposed as an attractive vehicle for vascular drug delivery, remain an orphan technology for enzyme therapies due to poor loading and inactivation of protein cargoes. To unite enzyme delivery by PNC with a clinically relevant goal of containment of vascular oxidative stress, a novel freeze-thaw encapsulation strategy was designed and provides similar to20% efficiency loading of an active large antioxidant enzyme, catalase, into PNC (200-300 nm) composed of biodegradable block copolymers poly(ethylene glycol)-b-poly(lactic-glycolic acid). Catalase's substrate, H2O2, was freely diffusible in the PNC polymer. Furthermore, PNC-loaded catalase stably retained 25-30% Of H2O2-degrading activity for at least 18 h in a proteolytic environment, while free catalase lost activity within 1 h. Delivery and protection of catalase from lysosomal degradation afforded by PNC nanotechnology may advance effectiveness and duration of treatment of diverse disease conditions associated with vascular oxidative stress. (C) 2004 Elsevier B.V. All rights reserved.