Department of Analytical Chemistry and Biomaterials, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.
Military Institute of Hygiene and Epidemiology, 4 Kozielska Str., 01-163 Warsaw, Poland.
Int J Mol Sci. 2023 Jan 5;24(2):1053. doi: 10.3390/ijms24021053.
Camptothecin (CPT) has demonstrated antitumor activity in lung, ovarian, breast, pancreas, and stomach cancers. However, this drug, like many other potent anticancer agents, is extremely water-insoluble. Furthermore, pharmacology studies have revealed that prolonged schedules must be administered continuously. For these reasons, several of its water-soluble analogues, prodrugs, and macromolecular conjugates have been synthesized, and various formulation approaches have been investigated. Biodegradable polyesters have gained popularity in cancer treatment in recent years. A number of biodegradable polymeric drug delivery systems (DDSs), designed for localized and systemic administration of therapeutic agents, as well as tumor-targeting macromolecules, have entered clinical trials, demonstrating the importance of biodegradable polyesters in cancer therapy. Biodegradable polyester-based DDSs have the potential to deliver the payload to the target while also increasing drug availability at intended site. The systemic toxicity and serious side-effects associated with conventional cancer therapies can be significantly reduced with targeted polymeric systems. This review elaborates on the use of biodegradable polyesters in the delivery of CPT and its analogues. The design of various DDSs based on biodegradable polyesters has been described, with the drug either adsorbed on the polymer's surface or encapsulated within its macrostructure, as well as those in which a hydrolyzed chemical bond is formed between the active substance and the polymer chain. The data related to the type of DDSs, the kind of linkage, and the details of in vitro and in vivo studies are included.
喜树碱(CPT)在肺癌、卵巢癌、乳腺癌、胰腺癌和胃癌中表现出抗肿瘤活性。然而,这种药物与许多其他强效抗癌剂一样,极难溶于水。此外,药理学研究表明,必须连续给予延长的方案。出于这些原因,已经合成了几种其水溶性类似物、前药和高分子缀合物,并研究了各种制剂方法。近年来,可生物降解聚酯在癌症治疗中越来越受欢迎。许多设计用于局部和全身给予治疗剂以及肿瘤靶向大分子的可生物降解聚合物药物递送系统(DDS)已进入临床试验,证明了可生物降解聚酯在癌症治疗中的重要性。基于可生物降解聚酯的 DDS 有可能在将有效载荷递送到靶标时增加药物在预期部位的可用性。与传统癌症疗法相关的全身毒性和严重副作用可以通过靶向聚合物系统显著降低。这篇综述详细阐述了可生物降解聚酯在 CPT 及其类似物递送中的应用。描述了基于可生物降解聚酯的各种 DDS 的设计,药物要么吸附在聚合物表面上,要么封装在其宏观结构内,以及在活性物质与聚合物链之间形成水解化学键的那些 DDS。包括与 DDS 类型、键合类型以及体外和体内研究的详细信息相关的数据。