Improvement of Doxorubicin Toxicity by Conjugation with a New Carrier in Rats with Hepatocellular Carcinoma

Abstract

Doxorubicin (DOX) is one of the most widely-used chemotherapeutic anticancer drugs. Doxorubicin (DOX) causes serious side effects on both healthy and normal tissue. Therefore, drug delivery systems are an important route to discover these difficulties. In recent years, there have been great interests in developing biodegradable nanoparticles as effective drug delivery systems (DDS). Amphiphilic block copolymers have been widely investigated as hydrophobic drug solubilizing agents in DDS. They can self-assemble into polymeric micelles and nanoparticles (NPs) in aqueous environments. Most polymeric micelles are composed of a hydrophobic block as the inner core and a hydrophilic block as the outer shell. The solubility of water increases by encapsulated of A hydrophobic drug in the hydrophobic core of the micelles. The hydrophilic shell is able to prolong the circulation time due to a decrease in phagocytosis and renal clearance. The particles can accumulate in tumor tissue where the polymeric micelles normally have average size of approximately 50 nm diameters through a mechanism called enhanced permeation and retention (EPR) effect rather than in normal tissues, this is due to the fact that tumor vessels are structurally irregular compared to normal vessels.

One of the most commonly used micelles in drug delivery applications is Pluronic, an amphiphilic tri-block copolymer, composed of poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO). Pluronic has low toxicity in the body and the ability to encapsulate any hydrophobic agents. However, the major problem of using polymeric micelles is their instability. To solve this problem, grafting pluronic with chitosan to form a copolymer was suggested. Chitosan is the cationic polysaccharide derived from chitin which stimulates cell growth and protein adsorption. Chitosan has been widely used in biomedical and pharmaceutical applications because of its biocompatibility and biodegradability. Although chitosan graft pluronic has been used in many forms such as hydrogel nano-aggregation and nanoparticles (NPs). In conclusion, in this study, a composite of DOX encapsulated nanoparticles delivery system was synthesized and characterized using a graft copolymer composed of O-Succinyl chitosan and Pluronic® F127 to reduce acute side effects of doxorubicin on heart.