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Aim: FG020326, a novel imidazole derivative, is a potent multidrug-resistance (MDR) modulator in vitro and in vivo. However, FG020326 is insoluble. PEDLLA-FG020326 is a FG020326-loaded nanoparticle formed with diblock eopolymers of poly (ethylene glycol)-bloek-poly (D,L-lactic acid) (PEG:PDLLA, PEDLLA) that can solubilize FG020326. This work was intended to evaluate the pharmacody-namics of PEDLLA-FG020326 on reversing MDR in vitro and in vivo.Methods: Cytotoxicity was determined by tetrazolium assay. The intraceUular accumulation and efflux of doxorubicin (Dox) were detected by fluorescence spectrophotometry.The function of P-glycoprotein was examined by Rhodamine 123 (Rh 123) accumu-lation detected by flow cytometry. The KBv200 cell xenograft model was estab-lished to investigate the effect of PEDLLA-FG020326 on reversing MDR in vivo.Results: PEDLLA-FG020326 and FG020326 exhibited 56.4- and 35.9-fold activity in reversing KBv200 cells to vincristine (VCR) resistance, respectively and 14.98-and 7.64-fold to Dox resistance, respectively. PEDLLA-FG020326 was much stron-ger than FG020326, resulting in the increase of Dox and Rh123 accumulation and the decrease of intracellular Dox extrusion in KBv200 cells. Importantly, PEDLLA-FG020326 exhibited more powerful activity than FG020326 in enhancing the effect of VCR against KBv200 cell xenografts in nude mice, but did not appear more toxic.Conclusion: The pharmacodynamics of FG020326 was improved by incorporating it into a micellar nanoparticle formed with PEG-block-PDLLA copolymers.