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具有分散疏水性纳米颗粒的 pH 响应水凝胶用于化疗药物的口服递送。

pH-responsive hydrogels with dispersed hydrophobic nanoparticles for the oral delivery of chemotherapeutics.

机构信息

Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA.

出版信息

J Biomed Mater Res A. 2013 Aug;101(8):2229-36. doi: 10.1002/jbm.a.34532. Epub 2012 Dec 28.

DOI:10.1002/jbm.a.34532
PMID:23281185
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3619027/
Abstract

Amphiphilic polymer carriers were formed by polymerizing a hydrophilic, pH-responsive hydrogel composed of poly(methacrylic-grafted-ethylene glycol) (P(MAA-g-EG)) in the presence of hydrophobic PMMA nanoparticles. These polymer carriers were varied in PMMA nanoparticle content to elicit a variety of physiochemical properties which would preferentially load doxorubicin, a hydrophobic chemotherapeutic, and release doxorubicin locally in the colon for the treatment of colon cancers. Loading levels ranged from 49% to 64% and increased with increasing nanoparticle content. Doxorubicin loaded polymers were released in a physiological model where low pH was used to simulate the stomach and then stepped to more neutral conditions to simulate the upper small intestine. P(MAA-g-EG) containing nanoparticles were less mucoadhesive as determined using a tensile tester, polymer samples, and fresh porcine small intestine. The cytocompatibility of the polymer materials were assessed using cell lines representing the GI tract and colon cancer and were noncytotoxic at varying concentrations and exposure times.

摘要

两亲性聚合物载体是通过在存在疏水性 PMMA 纳米粒子的情况下聚合由聚(甲基丙烯酸接枝-乙二醇)(P(MAA-g-EG))组成的亲水性、pH 响应水凝胶而形成的。这些聚合物载体中 PMMA 纳米粒子的含量不同,从而产生了各种物理化学性质,这些性质将优先负载多柔比星,一种疏水性化疗药物,并在结肠局部释放多柔比星,用于治疗结肠癌。载药量范围为 49%至 64%,并随纳米粒子含量的增加而增加。多柔比星负载的聚合物在生理模型中释放,其中使用低 pH 值模拟胃,然后切换到更中性的条件模拟上小肠。使用拉伸试验机、聚合物样品和新鲜猪小肠测定,含有纳米粒子的 P(MAA-g-EG)的粘膜粘附性较低。使用代表胃肠道和结肠癌的细胞系评估聚合物材料的细胞相容性,并且在不同浓度和暴露时间下均无细胞毒性。

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