Transporter targeted-carnitine modified pectin-chitosan nanoparticles for inositol hexaphosphate delivery to the colon: An in silico and in vitro approach

Orally targeted delivery systems have attracted ample interest in colorectal cancer management. In this investigation, we developed Inositol hexaphosphate (IHP) loaded Tripolyphosphate (Tr) crosslinked Pectin (Pe) Chitosan (Ch) nanoparticles (IHP@Tr*Pe-Ch-NPs) and modified them with l-Carnitine (CE) (CE-IHP@Tr*Pe-Ch-NPs) to improve uptake in colon cells. The formulated CE-IHP@Tr*Pe-Ch-NPs displayed a monodisperse distribution with 219.3 ± 5.5 nm diameter and 30.17 mV surface charge. Cell-line studies revealed that CE-IHP@Tr*Pe-Ch-NPs exhibited excellent biocompatibility in J774.2 and decreased cell viability in DLD-1, HT-29, and MCF7 cell lines. More cell internalization was seen in HT-29 and MCF7 due to overexpression of the OCTN2 and ATB0,+ transporter (CE transporters) compared to DLD-1. The cell cycle profile, reactive oxygen species, apoptosis, and mitochondrial membrane potential assays were performed to explore the chemo-preventive mechanism of CE-IHP@Tr*Pe-Ch-NPs. Moreover, the in-silico docking studies revealed enhanced interactive behavior of CE-IHP@Tr*Pe-Ch-NPs, thereby proving their targeting ability. All the findings suggested that CE-IHP@Tr*Pe-Ch-NPs could be a promising drug delivery approach for colon cancer targeting. [Display omitted] •Biocompatible Carnitine (CE) modified Phytic acid (IHP) loaded Pectin-Chitosan Nanoparticles (NPs) were prepared.•The CE-modified NPs controlled IHP release rates in the gastric milieu.•The CE-modified NPs targeted OCTN2 and ATB0,+ transporter present in HT-29, and MCF7 cell lines.•The CE-modified NPs were more cytotoxic to HT-29 and MCF7 cells than DLD-1 cells due to the expression of transporters.•Greater uptake of CE-modified NPs was observed in HT-29 and MCF7 than in DLD-1cells.