Development of novel biofunctionalized chitosan decorated nanocochleates as a cancer targeted drug delivery platform

Abstract

A new family of biofunctionalized chitosan decorated nanocochleates-mediated drug delivery system was developed that involves uniquely combining nanocochleates with anticancer drug for controlled drug release, targeted delivery, improved bioavailability with reduced toxicity. This system was developed by loading of doxorubicin (DOX) to nanocochleates (DOX-NC) through conversion of negatively charged dimyristoylphosphatidylcholine (DMPC) phospholipid and cholesterol-bearing vesicles on addition of calcium ions, followed by encapsulation DOX-NC with folic acid conjugated chitosan (FA-CHI-DOX-NC). The release of DOX indicated strong pH dependence and implies hydrogen-bonding interaction between nanocochleates and DOX. Formulated FA-CHI-DOX-NC demonstrated higher in-vitro anticancer activity in folate overexpressed human breast cancer MCF-7 cells. The targeting effect for the FA-CHI-DOX-NC was also demonstrated. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 9.1 µg/ml for DOX while it was decreased by 31.68% for the DOX-NC (6.2 µg/ml). Furthermore, the GI50 value of FA-CHI-DOX-NC was 4.4 µg/ml, i.e. a 51.64% decrease was observed as compared to DOX solution. Moreover, bioavailability of DOX from FA-CHI-DOX-NC increased by 4-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to DOX solution. The proposed strategy is advantageous in terms of targeted drug delivery and has high potential to address the current challenges in drug delivery. Thus, the prepared new carrier offers a novel formulation that combines the unique properties of a biodegradable material, chitosan and nanocochleates for biomedical applications.