||Sirolimus (SR) is used as an immunosuppressant drug to prevent organ rejection in kidney transplants. It is chemically a macrolide and isolated from the bacterium Streptomyces hygroscopicus in a soil sample. Of recent, it has potent antiproliferative properties and useful in the treatment of certain types of cancer. In our objective of the study, SR is chemically conjugated with Methoxy-polyethylene glycolic acid (mPEG COOH) and Poly(lactic-co glycolic acid)[PLGA]. Two polymeric SR conjugates (mPEG-SR and PLGA-SR) were characterized by UV-spectra, infrared (IR) spectra, 1H NMR spectra, matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and HPLC analyses. It was found to be structurally correlated among the chemical structures of SR, mPEG COOH-SR conjugate, PLGA-SR conjugate, PLGA and m-PEG COOH polymers. The MTT assay of mPEG-SR, PLGA conjugates were carried out on specific MCF-7(Estrogen positive) and MDA MB231 (Estrogen negative) breast cancer cell lines using tamoxifen as control. All results were showing the positive effects of mPEG-SR with IC50 values of 15 µg/ml and 1.5 µg/ml more active than tamoxifen with IC50 values of 28 µg/ml and 4.9 µg/ml on MDA-MB 231(estrogen negative) and MCF-7(estrogen positive) breast cancer cell lines in vitro, respectively. Whereas PLGA-SR conjugate was shown high activity on MCF-7(estrogen positive) with IC50 value of 1.2 µg/ml and less activity on MDA MB 231(estrogen negative) with IC50 value of more than 100 µg/ml. Both conjugates have not shown any cytotoxicity activity on 3T3 fibroblast normal cell lines. These results indicate that both conjugates may provide highly potent cytotoxicity activity against specific breast cancer types than SR alone. In conclusion, polymeric conjugation is a useful approach in drug delivery systems. These conjugates are basic precursors to formulate into a novel drug delivery system for better release and with increased good bioavailability with fewer side effects.