Objective: The sustained release implants which can be directly implanted in the tumor site by surgery seem to be a promising way for the treatment of tumors with several favorable advantages over systemic administration.In our previous studies, RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive linkage (RGD-PPCD), was a potential conjugate for tumor-targeted therapy.To further enhanced therapeutic efficacy of RGD-PPCD conjugate, the study focuses on the development of DOX and its conjugate implants using poly (DL-lactic-co-glycolic acid) (PLGA), poly (DL-lactic acid) (PLA) and polyethylene glycol (PEG) as carrier materials.Methods: The implants were prepared by a simple solvent evaporation method.Different formulations with varying ratios of three polymers were designed, prepared and evaluated on the basis of formability (viscosity, drying time and hardness) and in vitro release.Results: The optimized formulation was obtained with the 3:1 ratio of PLGA/PLA (w/w) and 1% PEG (wt %).The drug release behavior of DOX, PPCD and RGD-PPCD implants was similar according to the assessment of similarity factor f2.The release mechanism was consistent with zero-order release.50% of drug release for up to about 40 days showed significant sustained release effect of the implant formulation.Furthermore, in vivo biodistribution and antitumor efficacy of the implants were studied in mice bearing subcutaneous C6 glioma.The data of intratumoral residue of implants showed that in vivo drug release in implants seemed to be faster than in vitro release.The retention amount of RGD-PPCD released from implants in tumor was highest followed by that of PPCD implants, in 30 days after implantation, and finally that of free DOX implant.Corresponding, the RGD-PPCD implant exhibited the strongest antitumor activity compared with PPCD and free DOX implants.Conclusion: The study presents an exploratory research on developing macromolecule-drug conjugates into long effect implants, to reduce drug loss in systemic delivery and increase intratumoral drug concentration.It was suggested that the RGD-PPCD conjugate formulated by implants could have the potential advantage over systemic administration in treating gliomas.