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Some of the drugs are having very short half-life, to compensate this problem it is common practice to increase the dosage, frequency or prolongation of administration of drug to maintain effective therapeutic concentration in patient. In this study a drug delivery scaffold was designed and synthesized based on polyethylene glycol (PEG)- ethylene diamine tetra acetic acid (EDTA) based poly(amidoamine) (PAMAM) star polymer (with 16 primary amine group on surface). Cloxacillin, Cephalexin and Ciprofloxacin were used as a model drugs having short half life to conjugate with PEGylated dendrimer. These drugs were coupled to star polymer via ester bond. Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1 HNMR) was used to characterize the intermediate and drug-star-polymer conjugates. Invitro activity of derivatized drugs compared to standard drug alone, it was found that zone of inhibition obtained by both category of drugs (standard and derivatized drugs) are almost similar. That means drug derivatization does not altering the antibacterial activity of drugs. To investigate pharmacokinetic parameters, selected drugs alone and modified drugs [(Drug-PEG)16-Dendrimer] were intravenously injected into rats. All the modified drugs demonstrated a dramatic increase in half-life than drugs alone. These studies suggest the use of these new PEG based EDTA core dendrimer support as a valuable alternative for enhancing biological half-life of drugs.