Redox-responsive cystamine conjugated chitin–hyaluronic acid composite nanogels

Abstract

Nanoscale carriers were developed to overcome the challenging barriers for the targeted intracellular delivery of chemotherapeutic agents, in particular within tumors. We demonstrate redox responsive cystamine (Cys) conjugated hyaluronic acid (HA)–chitin (CNG) nanogels for the intracellular delivery of doxorubicin (DOX) within colon cancer cells. Chitin, having a slow degrading property, could make HA to slowly degrade, thus protecting the DOX from a sudden burst release, and HA, being a ligand for the CD44 receptor, are over expressed in colon cancer cells (HT-29). 150–200 nm sized DOX-HA-CNGs and DOX-HA-Cys-CNGs were developed and characterized by DLS, Zeta, TG/DTA, FT-IR, EDAX and rheological techniques. The composite nanogel preparations proved to be safe for intravenous administration because they were non-hemolytic and did not interfere with the coagulation cascade. Flow cytometric and fluorescent microscopic analysis proved the specific internalization of DOX-HA-CNGs within HT-29 cells (CD-44 +ve). MTT assay revealed the superior anti-proliferative activity of DOX-HA-Cys-CNGs in CD-44 +ve HT-29 cells compared to that in CD-44 −ve IEC-6 cells. Thus, HA-Cys-CNGs are proven to be a better carrier for the selective, redox responsive and intracellular delivery of DOX.