Glutathione and pH-responsive chitosan-based nanogel as an efficient nanoplatform for controlled delivery of doxorubicin

摘要

Incomplete delivery of drugs to the cancerous tissue and the drug resistance mechanisms limit the medical applications of anticancer drugs. Colloidal systems offers many advantages owing to the non-invasive way of drug administration as well as centralized delivery of anti-cancer drugs to tumor tissue. Nanogels (Ngs) as a part of these colloidal systems have a good perspective for their ability to incorporate and encapsulate low-molecular-mass drugs, bio-macromolecules, and proteins. Therefore, we developed pH and redox-responsive Ngs to provide a hopeful prospect for targeted delivery of anti-cancer drugs in cancer cells. For this purpose, chitosan (CS) was first modified with a chain transfer agent (CTA) and then, the polymerization of 2-Hydroxyethyl methacrylate (HEMA) monomer occurred to create (CTS-g-PHEMA). Hydroxyl groups of HEMA reacted with maleic anhydride molecules to prepare CTS-g-PHEMA-maleic acid (MAc). Finally, the double bonds of MAc were used for the grafting of N, N' bis(acryloyl) cystamine (BAC) as a crosslinker agent to prepare redox-sensitive Ngs. The biocompatibility, chemical structures, DOX loading capacity, content of the drug released and in-vitro cytotoxicity effects were also studied. As a result, it is expected that Ngs can be applied as a potential nanomedicine carrier for the treatment of cancer.