Detoxification of doxorubicin by nanosponge in the animal model (rabbit)

Abstract

Toxicity induced by drugs is the main complication with medicines that are being used in the treatment of cancer. Doxorubicin is an anthracycline antibiotic. However, use of doxorubicin (Dox) as a therapeutic agent is restricted due to cardiotoxicity, narrow therapeutic range and multi-drug resistance. So, the extra amount of doxorubicin should be removed from the blood to avoid adverse effects. The current research was planned to investigate the effect of nanosponge in the detoxification of doxorubicin in animal model (rabbits). PLGA-COOH (polylactic-co-glycolic acid) nanoparticle was coated with red blood cell membrane to form nanosponge. Nanosponge was characterized for size and charge distribution. The in vitro absorption study was done with doxorubicin + water and doxorubicin + blood. For in vivo study, rabbits were separated into three groups (n=3). 1^st Group was administered IV doxorubicin (7 mg/kg) and 2^nd group was administered doxorubicin and PLGA NPs while 3^rd group was administered doxorubicin and nanosponge. Blood was taken on 1^st, 3^rd, 5^th and 7^th day from all groups fand serum was separated. Biochemical parameters of heart, liver and kidney were measured. At 7^th day, survived animals were sacrificed. Heart tissues were collected for histopathological observation. Cardiac function parameters showed significant increase in LDH and CK-MB levels due to doxorubicin and nanosponge showed significantly decrease of these parameters while no effect on liver and kidney enzymes was found. Cardio toxic effects of doxorubicin were further confirmed by histopathological examination. All results showed that nanosponge might be used for treatment of doxorubicin induced dose- dependent cardiotoxicity.