A THERMALLY RESPONSIVE SHORT ELASTIN LIKE POLYPEPTIDE-DRUG CONJUGATE: SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION FOR TARGETED DELIVERY OF ANTICANCER DRUGS

Introduction: Among the several new strategies explored today to avoid the side effects in cancer chemotherapy. The concept of polymer-drug conjugates has shown considerable promise. In this context, genetically engineered long elastin like polypeptides (ELPs) have been examined recently as drug carriers. These ELPs, however, have certain limitations. Objective: It is our hypothesis that short synthetic ELPs can also be used as drug carriers so as to overcome these limitations. The purpose of this investigation was, therefore, to synthesize, characterize and evaluate a thermally responsive short ELP-Doxorubicin conjugate for targeted delivery. Methods: The ELP-Doxorubicin conjugate of molecular weight 1280 Da was synthesized and characterized by ESI-MS, FTIR and NMR studies. Turbidimetry, differential scanning calorimetry (DSC) and circular dichorism (CD) studies were carried out to evaluate its structural transition behavior. Cellular uptake and intracellular localization studies of the conjugate and the free drug were carried out by flow cytometry and confocal fluorescence microscopy, respectively. In vitro cytotoxicity of the conjugate was evaluated by the MTT assay method and compared with that of the free drug. Results: The results reveal that the short ELP synthesized exhibits structural transition behavior similar to naturally occurring long ELPs and delivers more drug molecules to intracellular space compared to the free drug. This structural transition behavior can also be exploited for targeting drugs to solid tumors using hyperthermia. Conclusion: As hypothesized our investigations clearly demonstrate that short thermally responsive ELPs are good carrier for targeting anticancer drugs to the intracellular space

ANTIOXIDANT ACTIVITY OF IPOMOEA LEARI

Abstract The antioxidant properties of four successive extracts of Ipomoea leari Paxton and the successive chloroform extract fraction, ILCF-28, were tested using standard in vitro and in vivo models. The amount of the total phenolic and flavonoid content was also determined. The successive chloroform extract, ILC and its fraction ILCF-28 exhibited strong scavenging effect on 2,2-diphenyl-2-picryl hydrazyl (DPPH), Nitric oxide, 2,2 -azino-bis (3ethylbenzo-thiazoline-6-sulphonic acid) diammonium salt (ABTS) radical cation, Reducing power, p-NDA and hydrogen peroxide methods. The free radical scavenging effect of ILC and ILCF-28 was comparable with that of reference antioxidants. The ILCF-28 having the highest content of phenolic compounds and strong free radical scavenging effect when administered orally to male albino rats at 100, 200 and 400mg/kg body weight for 7 days, prior to carbontetrachloride (CCl4) treatment, caused a signiï¬cant increase in the levels of catalase (CAT) and superoxide dismutase (SOD) and a signiï¬cant decrease in the levels of lipidperoxidation (LPO) in serum, liver and kidney, in a dose dependent manner, when compared to CCl4 treated control. These results clearly indicate the strong antioxidant property of the plant Ipomoea leari. The study provides a proof for the ethnomedical claims and reported biological activities. The plant has, therefore, very good therapeutic potential