Jelonek Katarzyna, Li Suming, Kasperczyk Janusz, Wu Xiaohan, Orchel Arkadiusz
Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Sklodowska 34 St., 41-819 Zabrze, Poland.
European Institute of Membranes, UMR CNRS 5635, University of Montpellier, Place Eugene Bataillon, 34095 Montpellier Cedex 5, France.
Mater Sci Eng C Mater Biol Appl. 2017 Jun 1;75:918-925. doi: 10.1016/j.msec.2017.03.006. Epub 2017 Mar 2.
Paclitaxel is one of the most efficient anticancer agents, but the conventional dosage formulations cause many side effects. PLA-PEG filomicelles are promising carriers of paclitaxel because high loading capacity and long term release can be achieved. Slow release of cytostatic drugs is very advantageous due to prolonged exposure of tumor cells to cytostatic over multiple cell cycles. The aim of this study was to evaluate the potential of bioresorbable PLA-PEG filomicelles for prolonged delivery of paclitaxel. Paclitaxel is encapsulated in PLLA-PEG filomicelles and PDLLA-PEG spherical micelles. Drug release was studied in PBS at 37°C at various pH values to elucidate the influence of polymer degradation on drug release. NMR, GPC and HPLC were used to follow polymer degradation and drug release. The release of paclitaxel is strongly dependent on the degradation of micelles. A biphasic drug release profile is observed for both PLLA-PEG and PDLLA-PEG micelles: slow release in the first phase and faster release in the second phase. Degradation is faster at acidic pH than at pH7.4, and PLLA-PEG filomicelles degrade less rapidly than PDLLA-PEG spherical micelles, leading to various rates of drug release. The correlation between degradation and drug release is very helpful for the development of novel drug carriers with tailored properties. Importantly, the cytotoxic activity of PLLA-PEG filomicelles was evidenced, thus showing their potential as carrier of antitumor drugs.
紫杉醇是最有效的抗癌药物之一，但传统剂型会引发诸多副作用。聚乳酸-聚乙二醇丝状胶束是很有前景的紫杉醇载体，因为其可实现高载药量和长效释放。由于肿瘤细胞在多个细胞周期中长时间接触细胞抑制剂，细胞抑制剂药物的缓慢释放非常有利。本研究的目的是评估可生物降解的聚乳酸-聚乙二醇丝状胶束用于紫杉醇长效递送的潜力。紫杉醇被包裹在聚左旋乳酸-聚乙二醇丝状胶束和聚消旋乳酸-聚乙二醇球形胶束中。在37℃下于不同pH值的磷酸盐缓冲盐溶液（PBS）中研究药物释放，以阐明聚合物降解对药物释放的影响。使用核磁共振（NMR）、凝胶渗透色谱（GPC）和高效液相色谱（HPLC）来跟踪聚合物降解和药物释放。紫杉醇的释放强烈依赖于胶束的降解。聚左旋乳酸-聚乙二醇和聚消旋乳酸-聚乙二醇胶束均观察到双相药物释放曲线：第一阶段为缓慢释放，第二阶段为较快释放。在酸性pH下的降解比在pH7.4时更快，且聚左旋乳酸-聚乙二醇丝状胶束的降解速度比聚消旋乳酸-聚乙二醇球形胶束慢，导致不同的药物释放速率。降解与药物释放之间的相关性对于开发具有定制特性的新型药物载体非常有帮助。重要的是，聚左旋乳酸-聚乙二醇丝状胶束的细胞毒性活性得到了证实，从而显示出它们作为抗肿瘤药物载体的潜力。
