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.

新型合成生物材料的设计和开发，可以充分溶解治疗剂，以适当的速度和位置释放它们，同时释放它们在人类中是安全的，这是这项研究的主要目的。这种化合物有望模仿生物传输系统的功能：被认为是体内的自我，将足够数量的药物携带到其作用部位，在其细胞和分子靶标附近释放其治疗货物，然后降解以使生物兼容的成分降解。在这种情况下，由于结构修饰，稳定性和给药的安全性，合成生物材料可能对它们的生物学有利。在该项目的第一部分中，我们开发了新型的自相关块共聚物，这些共聚物由聚（乙烯氧化物） - 聚（酯）s轴承轴承轴基或聚（酯）块上的芳族基团组成。由于聚合物的两亲性质，由于聚合物的两亲性质，由于聚（酯）而生物降解的聚（酯）可生物降解，因此，开发的块共聚物是生物兼容的。 聚酯纤维）。 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，但具有化学柔韧性的优势。在该项目的第二部分中，我们将寻求人工病毒的开发，以递送基于核酸的治疗剂。可以通过静电或疏水相互作用开发聚合物纳米载体，这些纳米载体可以通过静电或疏水相互作用融合DNA和RNA结构，并将其传递到适当的细胞内靶标。所提出的结构将基于生物相容性和可生物降解的聚（乙烷氧化乙烷） - 聚（酯）嵌段共聚物，该共聚物靶向靶向配体在聚（乙烷氧化物）壳上的配体以及疏水和阳离子和阳离子基团。