A Novel Strategy for the Delivery of Doxorubicin to Reduce Cardiotoxicity

Abstract

Doxorubicin (DOX) is an effective anticancer drug but its effectiveness is limited due to their toxicities after long term use required in cancer chemotherapy which leads to damage of the cardiac muscles and may be irreversible in nature. The approach based on novel drug delivery system gives the new hopes and ray of light to overcome the problems associated with the Dox as well as other anticancer drugs. In present research paper the DOX bearing nano-aggregates (DN) and folic acid conjugated DOX bearing nano-aggregates (FDN) were prepared to increase the therapeutics index of drug by enhancing the drug concentration at target site and avoiding their effect or by passing the healthy organ and cells. In present study PLGA-PEG block polymeric system was synthesized by ring opening polymerization techniques using NHS and then conjugated with DOX. The synthesis of F-PEG-PLGA-DOX was confirmed by 1H-nuclear magnetic resonance (NMR). Prepared nano-aggregates of DOX were studied for particle size, entrapment efficiency, in-vitro and in-vivo studies. The size of DN was found to be 135±0.6 nm whereas slightly increased size i.e. 141±0.8 nm was found in case of FDN. The %entrapment efficiency was found to be 79.3±0.5% and 71.7±0.5% of DN and FDN respectively. The in-vitro drug release studies show initially fast release of drug for 10 h. The in-vivo biodistribution studies showed the lesser uptake of DOX in heart in case of nano-aggregates formulation (DN and FDN) as compare to plain DOX after i.v. administration. This may be due to less concentration of free drug available for the absorption by the organ, which indirectly indicated that the drug may be available for targeting to the cancer cells via receptor mediated endocytosis due to the presence of folic acid with the nano-aggregates.