Preparation and Anti-cancer Evaluation of Methotrexate-loaded Inositol-6 Phosphate Cross-linked Chitosan Nanoparticles on Breast Cancer

Purpose: Chitosan nanoparticles (CNs) have directed considerable research efforts towards developing biocompatible, biodegradable, inexpensive and efficient particulate drug delivery systems. Methods: 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. Results: 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. Conclusion: Consequently, InsP6 can be presented as an accessible and cost-effective member of physical cross-linkers to prepare efficient CNs as drug delivery systems.