Bontha Venkata Subrahmanya Lokesh
UCSI University, Malaysia
Title: :Enhanced cytotoxic effect of chemically conjugated polymeric sirolimus against ht-29 colon cancer and a-549 lung cancer cell lines
Biography
Biography: Bontha Venkata Subrahmanya Lokesh
Abstract
Background/ Aim: Sirolimus (SR) is highly protein binding drug (92%) and lipophilic (log P=4.917) in nature. It has half life of 57-63 hrs and oral bioavailability is 20% even less when aft er eating food rich in fat. In our objective of the study, SR is chemically conjugated with biodegradable polymers like Methoxy-polyethylene glycolic acid (mPEG COOH) and Poly(Lacticco glycolic acid)(PLGA) .It was ensured that there is a structurally correlation among the chemical structures of SR, mPEG COOH-SR conjugate, PLGA-SR conjugate, PLGA and m-PEG COOH polymers. Methods/Materials: Th e cytotoxicity assay of both conjugates was carried out on specifi c A-549 lung cancer and HT-29 colon cancer cell lines using vincristine sulfate, tamoxifen and cisplatin as controls separately. Results: All results were showing the positive eff ects of PLGA-SR and cisplatin with IC50 values of 2.88 μg/ml and 9 μg/ml indicatively more active than cisplatin in vitro. Whereas mPEG-SR conjugate was similar activity of cisplatin with IC50 value of 8.88 μg/ml on A-549 lung cancer cell line. Both conjugates were not shown any cytotoxicity activity on 3T3 fi broblast normal cell lines. On the other hand, PLGA-SR conjugate was nine times more active than vincristine sulfate with IC50 value of 7 μg/ ml, where as MPEG-SR conjugate is more active than other controls and SR alone on HT-29 colon cancer cell line. Th ese results are indicated that both conjugates with potent cytotoxicity activity against specifi c lung cancer and colon cancer types than SR alone. Conclusion: Polymeric conjugation is a useful approach in a novel drug delivery system. Th ese conjugates are basic precursors to formulate into novel drug delivery systems especially in as nanocarriers for better release with surface modifi cation to enter the tumor cells with signifi cant increase in the bioavailability.