Department of Chemical Engineering , The University of Texas at Austin, Austin, TX 78712, USA.
J Biomater Sci Polym Ed. 2013;24(9):1027-40. doi: 10.1080/09205063.2012.731376. Epub 2012 Oct 15.
Biopolymers composed of a pH-responsive, hydrophilic poly(methacrylic acid-grafted-ethylene glycol) network polymerized in the presence of poly(methyl methacrylate) nanoparticles were designed for the oral delivery of chemotherapeutics for the treatment of colon cancer. An inulin-doxorubicin conjugate, designed to target the colon and improve doxorubicin efficacy, was loaded into these polymer carriers at an efficiency of 54%. Release studies indicated these polymer carriers minimized conjugate release in low pH conditions and released the conjugate at neutral pH conditions using a two-step pH experiment modeling the stomach and the small intestine. At lower concentration levels, the presence of the polymer carriers did not disrupt tight junctions as determined by transepithelial electrical resistance studies using Caco-2 and HT29-MTX cell lines which are an accurate model of the GI tract epithelia. Permeability values of unmodified doxorubicin and the inulin-doxorubicin conjugate in the presence of the polymer carriers were also determined using the same cell models and ranged from 1.87 to 3.80 × 10 (-6) cm/s.
生物聚合物由 pH 响应性、亲水性聚（甲基丙烯酸接枝-乙二醇）网络组成，在聚甲基丙烯酸甲酯纳米粒子的存在下聚合，用于治疗结肠癌的化疗药物的口服递送。设计了一种以菊糖-阿霉素缀合物为靶向物，以提高阿霉素的疗效，该缀合物以 54%的效率被负载到这些聚合物载体中。释放研究表明，这些聚合物载体在低 pH 条件下最小化了缀合物的释放，并在中性 pH 条件下使用两步 pH 实验释放缀合物，模拟胃和小肠。在较低的浓度水平下，聚合物载体的存在不会像通过使用 Caco-2 和 HT29-MTX 细胞系的跨上皮电阻研究来确定的那样破坏紧密连接，这些细胞系是胃肠道上皮的准确模型。同样使用相同的细胞模型，在聚合物载体存在的情况下，未修饰的阿霉素和菊糖-阿霉素缀合物的渗透值也被确定，范围从 1.87 到 3.80 × 10 ⁻ 6 cm/s。
