Preparation and Anti-cancer Evaluation of Methotrexate-loaded Inositol-6 Phosphate Cross-linked Chitosan...

Chitosan nanoparticles (CNs) have directed considerable research efforts towards developing biocompatible, biodegradable, inexpensive and efficient particulate drug delivery systems.

In the present investigation, we utilized green and safe inositol hexaphosphate (InsP6) as a physical cross-linker to obtain CNs (^InsP6CNs) and compared their size, zeta potential and cell uptake ability with the CNs cross-linked with tripolyphosphate (TPP) as a commonly used cross-linker (^TPPCNs). Methotrexate (MTX) as the model drug was physically incorporated within the both types of CNs (^InsP6CNs_MTX and ^TPPCNs_MTX) and their time-dependent anti-cancer behavior was evaluated on MCF-7 cell line.

Compared to ^TPPCNs, ^InsP6CNs were bigger in hydrodynamic diameter and showed far different zeta potential value. The MTX encapsulation efficiency was much higher for ^InsP6CNs_MTX than that of ^TPPCNs_MTX. ^InsP6CNs and ^TPPCNs showed similar in vitro cell uptake behavior, examined on MCF-7 cell line. Furthermore, after 24 h, ^InsP6CNs_MTX had the most in vitro antitumor effect on the MCF-7 cells, compared to free MTX and ^TPPCNs_MTX.

Consequently, InsP6 can be presented as an accessible and cost-effective member of physical cross-linkers to prepare efficient CNs as drug delivery systems.