BIODEGRADABLE HYDROPHILIC POLYACETALS

可生物降解的亲水性聚缩醛

• 批准号: 6394734
• 负责人: MIKHAIL I PAPISOV
• 金额: $ 12.34万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394734
• 关键词: biodegradable product; biomaterial compatibility; biomaterial development /preparation; biomimetics; copolymer; hydropathy; ketal; polymers

This is a resubmission of grant application 1 R21 RR14221-01. The goal of this project is to provide new biodegradable, non- toxic macromolecular materials with minimized biological reactivity for advanced applications in pharmacology and bioengineering. The project addresses the fundamental problem of developing an "ideally biocompatible" material. This material must be non- recognizable by any biomolecules and receptors, non-vulnerable to "non-specific" interactions, stable in physiological conditions and, at the same time, metabolizable by cells (e.g., phagocytes). Presently, such materials are not available, and no rational nor other approaches to their development have been reported. In this study, we utilize a novel, "biomimetic" approach to developing biocompatible materials. The underlying mechanistic hypothesis of this work suggests that minimally bioreactive biodegradable polymers can be obtained via partial emulation of natural interface structures formed by oligo- and polycarbohydrates on cell surfaces and biomolecules (glycolipids, glycoproteins, etc.). Polymer structure should comprise the biologically inert structural fragments of interface carbohydrates, e.g., the acetal group (O-C-O) and the surrounding carbons, whereas the potentially biorecognizable structures formed by C1-C2-C3-C4 must be absent. Experimental samples of a lead biomimetic polyacetal, (poly[hydrohymethylethylene hydroxymethylformal]) (PHF), demonstrated excellent biocompatibility, extremely low toxicity and negligible interactions in vivo in a sensitive graft copolymer circulation test. The objective of this research is two-fold: (1) to further test the hypothesis of general bio- inertness of hydrophilic polyacetals; and (2) to initiate translation of the concept into a new biomedical technology on the basis of PHF. The expected outcome of this study includes: new knowledge on interaction of hydrophilic polyacetals with biological systems; new technologies for producing advanced materials for bioengineering, pharmacology, and biomedical research; new molecular tools for biomedical research; and a methodological basis for future preclinical studies.

这是资助申请1 R21 RR 14221 -01的重新提交。本项目的目标是提供新的生物可降解的，无毒的高分子材料，最小化生物反应性的先进应用在药理学和生物工程。该项目解决了开发“理想生物相容性”材料的基本问题。 这种材料必须是任何生物分子和受体都不能识别的，不易受“非特异性”相互作用的影响，在生理条件下稳定，同时可被细胞代谢（例如，吞噬细胞）。目前，还没有这种材料，也没有关于开发这种材料的合理方法或其他方法的报告。在这项研究中，我们利用一种新的，“仿生”的方法来开发生物相容性材料。 这项工作的基本机制假设表明，最低限度的生物活性的生物可降解聚合物可以通过部分仿真的天然界面结构形成的寡和多碳水化合物的细胞表面和生物分子（糖脂，糖蛋白等）。 聚合物结构应该包括界面碳水化合物的生物惰性结构片段，例如，乙缩醛基（O-C-O）和周围的碳，而由C1-C2-C3-C4形成的潜在生物可识别结构必须不存在。实验样品的铅仿生聚缩醛，（聚[羟甲基乙烯羟甲基缩甲醛]）（PHF），表现出良好的生物相容性，极低的毒性和可忽略不计的相互作用，在体内敏感的接枝共聚物循环测试。 本研究的目的是双重的：（1）进一步检验亲水性聚缩醛的一般生物惰性的假设;和（2）在PHF的基础上开始将该概念转化为新的生物医学技术。本研究的预期成果包括：亲水性聚缩醛与生物系统相互作用的新知识;生产生物工程，药理学和生物医学研究先进材料的新技术;生物医学研究的新分子工具;以及未来临床前研究的方法学基础。

项目成果

Fully degradable hydrophilic polyals for protein modification.

• DOI: 10.1021/bm049210k
• 发表时间: 2005-08
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: A. Yurkovetskiy;Sungwoong Choi;A. Hiller;M. Yin;Catherine D. McCusker;S. Syed;A. Fischman;M. Papisov

Semisynthetic hydrophilic polyals.

半合成亲水性聚醛。

• DOI: 10.1021/bm0502157
• 发表时间: 2005
• 期刊: Biomacromolecules
• 影响因子: 6.2
• 作者: Papisov,MikhailI;Hiller,Alexander;Yurkovetskiy,Alexander;Yin,Mao;Barzana,Marlene;Hillier,Shawn;Fischman,AlanJ
• 通讯作者: Fischman,AlanJ

Synthesis of a macromolecular camptothecin conjugate with dual phase drug release.

• DOI: 10.1021/mp0499306
• 发表时间: 2004-08
• 期刊: Molecular pharmaceutics
• 影响因子: 4.9
• 作者: A. Yurkovetskiy;A. Hiller;S. Syed;M. Yin;X. Lu;A. Fischman;M. Papisov