Conjugation of folic acid with poly (NVCL-co-PEGMA)-grafted chitosan as a new doxorubicin delivery system

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.