Panahi Morteza, Rahbari-Sisakht Masoud, Faramarzi Mehdi
Department of Chemical Engineering, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran.
Department of Chemical Engineering, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran.
Int J Biol Macromol. 2023 May 1;236:123933. doi: 10.1016/j.ijbiomac.2023.123933. Epub 2023 Mar 11.
This paper aimed to investigate the synthesis of a novel drug delivery system (DDS) to target tumors and implement the controlled release of doxorubicin (DOX). Chitosan was modified with 3-mercaptopropyltrimethoxysilane and subjected to graft polymerization to implement grafting with the biocompatible thermosensitive copolymer of poly (NVCL-co-PEGMA). A folate receptor-targeting agent was obtained by attaching folic acid. The DDS loading capacity for DOX via physisorption was obtained to be 846.45 mg/g. The synthesized DDS showed temperature- and pH-sensitive drug release behavior in vitro. A temperature of 37 °C and a pH of 7.4 hindered the DOX release, whereas a temperature of 40 °C and a pH of 5.5 led to DOX release acceleration. In addition, the release of DOX was found to occur in a Fickian diffusion mechanism. The MTT assay tests indicated that the synthesized DDS was not detectably toxic to cell lines of breast cancer, while the toxicity of the DOX-loaded DDS was found to be substantial. The cell absorption enhancement of folic acid led to higher cytotoxicity of the DOX-loaded DDS than bare DOX. As a result, the proposed DDS could be a promising alternative for the targeted therapy of breast cancer through controlled drug release.
本文旨在研究一种新型靶向肿瘤的药物递送系统(DDS)的合成,并实现阿霉素(DOX)的控释。壳聚糖用3-巯基丙基三甲氧基硅烷改性,然后进行接枝聚合,以实现与生物相容性热敏感共聚物聚(N-乙烯基己内酰胺-co-聚乙二醇甲基丙烯酸酯)的接枝。通过连接叶酸获得叶酸受体靶向剂。通过物理吸附得到的DDS对DOX的负载量为846.45 mg/g。合成的DDS在体外表现出温度和pH敏感的药物释放行为。37°C的温度和7.4的pH值阻碍了DOX的释放,而40°C的温度和5.5的pH值导致DOX释放加速。此外,发现DOX的释放以菲克扩散机制发生。MTT法检测表明,合成的DDS对乳腺癌细胞系无明显毒性,而载有DOX的DDS毒性较大。叶酸对细胞吸收的增强导致载有DOX的DDS比单纯DOX具有更高的细胞毒性。因此,所提出的DDS有望成为通过控释实现乳腺癌靶向治疗的替代方案。