Chemical tailoring of micelle-forming poly(ethylen oxide)-block-poly(ester) copolymers for drug delivery

用于药物输送的胶束形成聚环氧乙烷-嵌段聚(酯)共聚物的化学剪裁

• 批准号: 261196-2008
• 负责人: Lavasanifar, Afsaneh
• 金额: $ 1.75万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=496755
• 关键词: Chemical; tailoring; micelle; forming; poly

Design and development of novel synthetic biomaterials that adequately solubilize therapeutic agents, release them in an appropriate rate and location, and at the same time, are safe for application in humans is the main purpose of this research. Such compounds are expected to mimic the function of biological transport systems: be recognized as self within the body, carry adequate quantities of the drug to its site of action, release their therapeutic cargo in the vicinity of their cellular and molecular targets and degrade to biocompatible components afterwards. In this context, synthetic biomaterials may be advantageous to their biological counterparts due to the ease of structural modifications, stability and safety of administration. In the first part of this project, we have developed novel self associating block copolymers consisting of poly(ethylene oxide)-poly(ester)s bearing pendent carboxyl or aromatic groups on the poly(ester) block. The developed block copolymers are bio-compatible due to the poly(ethylene oxide), biodegradable due to poly(ester), can self associate to nanoscopic micellar structures due to the amphiphilic nature of the polymer, and allow chemical conjugation and/or physical interaction with hydrophobic or hydrophilic molecules within the micellar core due to the presence of different side groups on the poly(ester). These biomaterials structurally and functionally are close to natural drug carriers in blood, i.e., lipoprotein, but have the advantage of chemical flexibility. In the second part of the project, we will pursue development of artificial viruses for the delivery of nuclearic acid based therapeutics. Development of polymeric nano-carriers that can incorporate DNA and RNA structures by electrostatic or hydrophobic interactions and deliver them to appropriate intracellular targets will be pursued. The proposed structures will be based on biocompatible and biodegradable poly(ethylene oxide)-poly(ester) block copolymers bearing targeting ligands on the poly(ethylene oxide) shell and hydrophobic and cationic groups in the poly(ester) core.

本研究的主要目的是设计和开发新型合成生物材料，使其充分溶解治疗药物，以适当的速率和位置释放药物，同时安全地应用于人体。这些化合物有望模拟生物运输系统的功能：在体内被识别为自身，携带足够量的药物至其作用部位，在其细胞和分子靶标附近释放其治疗货物，然后降解为生物相容性组分。在这种情况下，合成生物材料由于易于结构修饰、稳定性和给药安全性而可能对其生物对应物有利。在本项目的第一部分中，我们开发了新型的自缔合嵌段共聚物，它由聚环氧乙烷-聚酯组成，聚酯嵌段上带有羧基或芳香族侧基。所开发的嵌段共聚物由于聚（环氧乙烷）而具有生物相容性，由于聚（酯）而具有生物可降解性，由于聚合物的两亲性质而可以自缔合到纳米级胶束结构，并且由于聚（酯）上存在不同的侧基而允许与胶束核心内的疏水或亲水分子的化学缀合和/或物理相互作用。 这些生物材料在结构和功能上接近于血液中的天然药物载体，即，脂蛋白，但具有化学灵活性的优点。在该项目的第二部分，我们将继续开发用于核酸治疗的人工病毒。将继续开发聚合物纳米载体，其可以通过静电或疏水相互作用将DNA和RNA结构结合并将其递送到适当的细胞内靶点。所提出的结构将基于生物相容性和生物可降解的聚（环氧乙烷）-聚（酯）嵌段共聚物，其在聚（环氧乙烷）壳上具有靶向配体，在聚（酯）核中具有疏水性和阳离子基团。