Abstract
Toxic outcome of chemical therapeutics as well as multidrug resistance are two serious phenomena for their inacceptance in cancer chemotherapy. Antioxidants like curcumin (Cur) have gained immense importance for their excellent anticarcinogenic activities and minimum toxic manifestations in biological system. However, Cur is lipophilic and thus following oral administration hardly appears in blood indicating its potential therapeutic challenge in cancer therapy. Nanocapsulated Cur has been used as a drug delivery vector to focus the effectiveness of these vesicles against hepatocellular carcinoma. The theme of work was to evaluate effectiveness in oral route of polylactide co-glycolide (PLGA) Nanocapsulated curcumin (Nano Cur) against diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in rat. Nano Cur of average diameter 14nm and encapsulation efficiency of 78% were prepared. Fourier Transform Infra Red (FTIR) analysis revealed that there is no chemical interaction between drug and the polymer. Three i.p. injections of the chemical hepatocarcinogen DEN at 15days interval causes hepatotoxicity, the generation of reactive oxygen species (ROS), lipid peroxidation, decrease in plasma membrane microviscosity and depletion of antioxidant enzyme levels in liver. Nano Cur (weekly oral treatment for 16weeks at 20mg/kg b.wt) in DEN induced HCC rats exerted significant protection against HCC and restored redox homeostasis in liver cells. Nanocapsulated Cur caused cancer cell apoptosis as visualized by ApoBrdU analysis. Histopathological analysis confirmed the pathological improvement in the liver. Nano Cur was found to be a potential formulation in oral route in combating the oxidative damage of hepatic cells and eliminating DEN induced hepatocellular cancer cells in rat whereas identical amount of free Cur treatment was found almost ineffective.
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