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: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=394898
• 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.

设计和开发新的合成生物材料，充分溶解治疗剂，以适当的速度和位置释放它们，同时对人体安全应用是本研究的主要目的。这类化合物有望模仿生物运输系统的功能：在体内被识别为自身，携带足够数量的药物到其作用部位，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的成分。在这种情况下，合成生物材料可能比它们的生物同行更有利，因为它易于结构修改，稳定性和给药安全。在本项目的第一部分，我们开发了一种新型的自缔合嵌段共聚物，该嵌段由聚氧乙烷-聚酯-S组成，聚酯嵌段上含有侧羧基或芳基。所开发的嵌段共聚物由于聚环氧乙烷是生物相容的，由于聚酯是可生物降解的，由于聚合物的两亲性可以自结合到纳米胶束结构上，并且由于聚酯上存在不同的侧基，允许与胶束核心内的疏水或亲水分子进行化学共轭和/或物理相互作用。这些生物材料在结构和功能上都接近血液中的天然药物载体，即脂蛋白，但具有化学灵活性的优势。在该项目的第二部分，我们将继续开发用于输送基于核酸的疗法的人造病毒。将继续开发能够通过静电或疏水相互作用结合DNA和RNA结构并将其输送到适当的细胞内靶标的聚合物纳米载体。建议的结构将基于生物相容和可生物降解的聚环氧乙烷-聚酯嵌段共聚物，在聚环氧乙烷外壳上含有靶向配体，在聚酯核中含有疏水和阳离子基团。