以聚乙二醇-聚己内酯为载体的药物传递系统在抗肿瘤中的应用

Drug delivery system based on PEG-PCL copolymer for cancer treatment

化疗在肿瘤治疗中还是发挥着主导作用,但随着药物的广泛应用,多药耐药已经成为当前亟待解决的问题,同时,极低的水溶性也是化疗药物在临床应用的一大障碍。制剂新技术的出现及生物可降解材料的不断发展,为这些问题的解决提供了可能。聚乙二醇-聚己内酯(PEG-PCL)是一种被广泛应用的载体材料:脂肪族聚酯PCL具有高度的生物相容性、生理无毒性和生物可降解性,但由于疏水性太强,容易被蛋白质吸附和网状内皮细胞识别并捕捉,在体内的循环时间短;而PEG是一种非离子型的水溶性嵌段,它不仅可以提高PCL的水溶性避免被网状内皮系统吞噬,起到长循环作用,而且PEG具有可被修饰的羟基,既可以实现PEG-PCL间的修饰,也可被靶分子、细胞穿膜肽等修饰达到靶向目的。本文将就PEG-PCL及被修饰的PEG-PCL作为药物载体在肿瘤治疗中的特殊功效进行讨论和述评。

Chemotherapy still plays an important role in cancer treatment. However, muhidrug resistance （MDR） became the biggest problem with the wide use of drugs and it requires to be solved immediately. Low water-solubility is also a major obstacle which limits the use of chemotherapy in clinic. With the development of biodegradable materials and novel preparation techniques in drug delivery system, the solutions to problems mentioned above become a possibility. PEG-PCL has been widely used in drug delivery system. Aliphatic polyester PCL is biocompatible, nontoxic, and biodegradable, but can be eliminated quickly by reticuloendothelial cells. PEG, a nontoxic water-soluble segment, can not only improve the water-solubility of PCL to protect it from being eliminated by reticuloendothelial cells, but can also be modified to target tumor cells. Because of the special pathological structure of tumor which can result in enhanced permeability and retention （EPR） effect, it is important to control the size of drug delivery system to achieve passive targeting. What＇s more, some specific covalent bonds which can be cleaved in acidic tumor tissues or by the over-expressed protein in cancer cells have also been applied between the block of PEG and PCL： hydrazone bond, amido bond, ester bond, and disulfide bond. In addition, some target molecules and cell penetrating peptides have also been conjugated to PEG to target the corresponding receptors overexpressed on the surface of cancer ceils. This article will summarize the targeting effect of drug delivery systems via either passive or active targeting based on PEG-PCL copolymer for cancer treatment.