Surface charge effect on mucoadhesion of chitosan based nanogels for local anti-colorectal cancer drug delivery

To develop more effective anticancer mucoadhesive drug delivery system for the treatment of colorectal cancer, chitosan based nanogels (NGs) were prepared by electrostatic interaction between chitosan (CS) and carboxymethyl-chitosan (CMCS). By respectively using tripolyphosphate (TPP) and CaCl₂ as ionic crosslinker, two well-characterized doxorubicin hydrochloride (DOX) loaded NGs with opposite zeta potential (DOX:CS/CMCS/TPP NGs, -32.6±1.1mV and DOX:CS/CMCS/Ca²⁺ NGs, +31.8±0.9mV) were obtained. Compared with DOX:CS/CMCS/TPP NGs, DOX:CS/CMCS/Ca²⁺ NGs were taken up to a greater extent by colorectal cancer cells, resulting in greater reduction in percentage of cell viability. Owing to high binding capability to mucin and inhibited paracellular transport by colon, DOX:CS/CMCS/Ca²⁺ NGs exhibited improved mucoadhesion and limited permeability. This is beneficial to prolong the contact time of formulation onto intestinal mucosa and improved local drug concentration. The results provided evidence DOX:CS/CMCS/Ca²⁺ NGs to be exciting and promising for the treatment of colorectal cancer.