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首页> 外文期刊>Advanced Functional Materials >Injectable Hydrogels from Triblock Copolymers of Vitamin E-Functionalized Polycarbonate and Poly(ethylene glycol) for Subcutaneous Delivery of Antibodies for Cancer Therapy
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Injectable Hydrogels from Triblock Copolymers of Vitamin E-Functionalized Polycarbonate and Poly(ethylene glycol) for Subcutaneous Delivery of Antibodies for Cancer Therapy

机译：维生素E功能化聚碳酸酯和聚乙二醇三嵌段共聚物的可注射水凝胶，用于皮下递送癌症治疗用抗体

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In this study, 'ABA'-type triblock copolymers of vitamin E-functionalized polycarbonate and poly(ethylene glycol), i.e., VitE_m-PEG-VitE_m, with extremely short hydrophobic block VitE_m, are synthesized and employed to form physically cross-linked injectable hydrogels for local and sustained delivery of Herceptin. The hydrogels are formed at low concentrations (4-8 wt%). By varying polymer composition and concentration, the rheological behavior, porosity, and drug release properties of hydrogels are readily tunable. The in vitro antitumor specificity and efficacy of Herceptin in hydrogel and solution are investigated by MTT assay against normal and human breast cancer cell lines with different HER2 expression levels. The results demonstrate that the Herceptin-loaded hydrogel is specific towards HER2-overexpressing cancer cells and cytotoxic action is comparable to that of the Herceptin solution. The biocompatibility and biodegradability of hydrogel are evaluated in mice with subcutaneous injection by histological examination. It is observed that the hydrogel does not evoke a chronic inflammatory response and degrades within 6 weeks post administration. Biodistribution and anti-tumor efficacy studies performed in BT474 tumor-bearing mice show that single subcutaneous injection of Herceptin-loaded hydrogel at a site close to the tumor enhances the retention of the antibody within the tumor. This leads to superior anti-tumor efficacy as compared to intravenous (i.v.) and subcutaneous (s.c.) delivery of Herceptin in solution. The tumor size shrank by 77% at Day 28. When the hydrogel is injected at a distal location away from the tumor site, anti-tumor efficacy is similar to that of weekly i.v. injections of Herceptin solution over 4 weeks, with the number of injections reduced from 4 to 1. These findings suggest that this hydrogel has great potential for use in subcutaneous and sustained delivery of antibodies to increase therapeutic efficacy and/or improve patient compliance.
机译：在这项研究中，合成了维生素E功能化聚碳酸酯和聚乙二醇的“ ABA”型三嵌段共聚物，即VitE_m-PEG-VitE_m，具有非常短的疏水嵌段VitE_m，并用于形成物理交联的注射剂用于局部和持续递送赫赛汀的水凝胶。水凝胶以低浓度（4-8重量％）形成。通过改变聚合物的组成和浓度，水凝胶的流变行为，孔隙率和药物释放特性很容易调整。通过MTT试验研究了荷塞汀在水凝胶和溶液中的体外抗肿瘤特异性和功效，以对抗具有不同HER2表达水平的正常和人乳腺癌细胞系。结果表明，装有赫赛汀的水凝胶对过表达HER2的癌细胞具有特异性，其细胞毒性作用与赫赛汀溶液相当。通过组织学检查在皮下注射的小鼠中评估水凝胶的生物相容性和生物降解性。观察到水凝胶不会引起慢性炎症反应，并且在给药后6周内降解。在携带BT474的荷瘤小鼠中进行的生物分布和抗肿瘤功效研究表明，在接近肿瘤的部位进行皮下注射荷赛汀水凝胶的单次注射可增强抗体在肿瘤内的保留。与溶液中赫赛汀的静脉内（i.v.）和皮下（s.c.）递送相比，这导致优异的抗肿瘤功效。在第28天，肿瘤尺寸缩小了77％。当在远离肿瘤部位的远侧位置注射水凝胶时，抗肿瘤功效类似于每周一次静脉内注射。在4周内注射Herceptin溶液，注射次数从4减少到1。这些发现表明，这种水凝胶具有用于皮下和持续递送抗体以提高治疗功效和/或改善患者依从性的巨大潜力。

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  • 来源
    《Advanced Functional Materials》 |2014年第11期|1538-1550|共13页
  • 作者

    Ashlynn L. Z. Lee; Victor W. L. Ng; Shujun Gao; James L. Hedrick; Yi Yan Yang;

  • 作者单位

    Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos Singapore 138669, Singapore;

    Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos Singapore 138669, Singapore;

    Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos Singapore 138669, Singapore;

    IBM Almaden Research Center 650 Harry Road, San Jose, CA 95120, USA;

    Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos Singapore 138669, Singapore;

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