Authors: DENG, Wen-jing¹; YANG, Xiao-qiang²; LIANG, Yong-ju¹; CHEN, Li-ming¹; YAN, Yan-yan¹; SHUAI, Xin-tao²; FU, Li-wu

Source: Acta Pharmacologica Sinica, Volume 28, Number 6, June 2007 , pp. 913-920(8)

Publisher: Wiley-Blackwell

Abstract:

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 copolymers of poly (ethylene glycol)-block-poly (D,L-lactic acid) (PEG:PDLLA, PEDLLA) that can solubilize FG020326. This work was intended to evaluate the pharmacodynamics of PEDLLA-FG020326 on reversing MDR in vitro and in vivo.Methods: Cytotoxicity was determined by tetrazolium assay. The intracellular accumulation and efflux of doxorubicin (Dox) were detected by fluorescence spectrophotometry. The function of P-glycoprotein was examined by Rhodamine 123 (Rh123) accumulation detected by flow cytometry. The KBv200 cell xenograft model was established 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 stronger 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.

Keywords: FG020326; micellar nanoparticle; multidrug resistance; xenografts

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2007.00565.x

Affiliations: 1: State Key Laboratory of Oncology in Southern China Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China 2: School of Chemistry and Chemical Engineering of Sun Yat-Sen University, Guangzhou 510275, China

Publication date: 2007-06-01

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: DENG, Wen-jing ;  YANG, Xiao-qiang ;  LIANG, Yong-ju ;  CHEN, Li-ming ;  YAN, Yan-yan ;  SHUAI, Xin-tao ;  FU, Li-wu

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers