Polymeric micelle/nano hydrogel composite matrix as a novel multi-drug carrier

Abstract

According to the World Health Organization (WHO), fatality of cancer is 9.6 million in 2018. Of these, 1.8 million deaths are due to colorectal cancer. However, it doesn't seem that proper medications are unavailable. Instead, the medications should reach the site of action without causing any further side effects. With the advent of smart biomaterials this target is on its verge to be achieved. Previous reports prove that the side effects induced by Cisplatin (CIS) could be greatly decreased by curcumin (CUR). Hence, if these two drugs are used in unison, greater efficacy with lesser toxicity could be achieved. However, to incorporate two drugs and to release them simultaneously without any premature leakage can be achieved by polymeric micelles. To increase the core and hydrophobicity, monomers with large alkyl chains like triethylene tetraamine (TETA) and oleic acid (OA) were grafted to the backbone of heparin (HEP) skeleton. To target these drugs, folic acid was entrapped within hydroxyl appetite (HAP) based hydrogel and was dispersed onto polymeric micelle (PM). This coating could further act as a potential barrier to sustain the drug release as evident from similar previous studies. All the reaction steps were monitored using FTIR, XRD, H1 NMR, DLS and SEM studies. The in vitro swelling and release studies proved promising with folic acid showing burst release followed by the sustained release of chemotherapeutic drugs. The efficacy was further ascertained by MTT assay on normal and HCT 116 colon cancer cell lines. This was further proved by fluorescence studies. Thus, the present material could act as a promising candidate for the treatment of colorectal cancer with high efficacy and minimal toxicity.