Potential in vitro and in vivo colon specific anticancer activity on HCT- 116 Xenograft Nude mice model: Targeted delivery using enteric coated folate modify nanoparticles

Abstract

Aim: The aim of the study was to develop a drug delivery system for specific targeting in colon cancer. We have developed Eudragit S-100 (ES) coated folic acid (FA) conjugated gliadin (Gd) delivery system for the effective targeting to the over expressed folate receptors (FRs) in colon cancer. Method: The FA conjugate with Gd (FA-Gd) was synthesized and characterized by FTIR and 1H NMR, this developed conjugated was used to prepare curcumin (CU) loaded nanoparticles (NP) by desolvation method. Result: FA-CU-GdNP was further coated with ES and ES-FA-CU-GdNP was obtained. The ES-FA-CU-GdNP were also capable of inducing cell caspase dependent apoptosis in Caco-2 cell lines and exhibit DNA intercalating activity. In therapeutic experiments the ES-FA-CU-GdNP was administered orally to HCT-116 tumor bearing nude mice. In vivo data of bio-distribution showed that ES-FA-CU-GdNP delivered maximum amount of NP in the colon and tumor, respectively after 12 hours, reflecting its targeting potential to the colon and tumor. Gamma scintigraphy study suggested that ES-FA-CU-GdNP at low pH and released NP slowly at pH 7.4 in the colon. Conclusion: These studies provide evidences that ES-FA-CU-GdNP holds promise to address over-expressed FRs in colorectal cancer and were found to be safe for oral administration for prolonged duration.