Synthesis and valuation of novel nanohydrogel for the Dual-Drug Delivery of methotrexate and cisplatin

Co-delivery of two drugs in one nanoparticle is increasingly used to overcome for example multi-drug resistance in cancer therapy and therefore suitable drug carriers need to be developed. In this work, using reversible addition–fragmentation chain transfer polymerization method a novel nanohydrogel based on poly (hydroxyl ethyl methacrylate), PEGDA and EDTA, was employed as a reactive scaffold for the attachment of methotrexate (MTX) and cisplatin prodrug. The synthesized structure was confirmed by Fourier-transform infrared spectroscopy and proton nuclear magnetic resonance methods. The pH responsive behavior of the synthesized particles was checked by size measurement in two different pH values (5.5 and 7.4) by dynamic light scattering and transmission electron microscopy. The release profiles of nanoparticles carrying drug molecules were checked in two different simulated pH of healthy organs (7.4) and tumor site (5.5). Despite lower release in pH of 7.4, an increased drug release was obtained in pH of 5.5. The in vitro toxicity assay was performed on SW 480 as a colorectal cancer cell line, which showed a time dependency cellular entrance, an enhanced cytotoxicity by the drugs loaded nanoparticles. The suitable size (<200nm), pH responsive behavior and anti-proliferative activity in cancer cells and hemocompatibility were the noticeable features of the developed dual drugs adsorbed nanoparticle, which introduced this formulation as an ideal vehicle in anti-cancer drug delivery.

Keywords:

RAFT synthesis , Nanohydrogel , EDTA , Methotrexate , Cisplatin , Dual drug delivery.