Evaluation of pluronic nanosuspensions loading a novel insoluble anticancer drug both in vitro and in vivo.
To improve the solubility, stability and the antitumor activity of a novel anticancer drug, 3-(4-bromopheny l)-2-(ethyl-sulfonyl)-6-methylquinoxaline1,4-dioxide (Q39), a poloxamer nanosuspension was developed by precipitation combined with high pressure homogenization in present study. In vitro characterizations of Q39 nanosuspension (Q39/NS), including particle size, polydispersity index (PI), morphology, crystalline, saturation solubility, stability and releases were evaluated. BABL/c nude mice bearing HepG2 cells were used as in vivo tumor models to evaluate the anti-tumor activity of Q39/NS after intravenous administration. The particle size and PI for Poloxamer188 nanosuspension (P188/NS) were (304±3) nm, and (0.123±0.005) respectively, and it was (307±5) nm and (0.120±0.007) for Poloxamer85 nanosuspension (P85/NS) correspondingly. The morphology of P188/NS was spherical shape while elliptoid shape for P85/NS. The crystalline of Q39/NS did not change as shown by the X-ray diffraction analysis. The stability of Q39/NS improved compared with the solution. The solubility of Q39 in P188/NS was 7.3 times higher than the original solubility, while it was 6 times for P85/NS. Sustained release as shown from the in vitro release test, together with the tumor-targeting as shown from in vivo NS distribution, may contribute to the enhanced in vivo antitumor activity of Q39/NS.
Zhejiang Province Key Laboraotory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, PR China.
Xin-Jiang
XJ
Tang
Ying-Hua
YH
Fu
Qing-Hua
QH
Meng
Li-Ming
LM
Li
Xiao-Ying
XY
Ying
Min
M
Han
Qiao-Jun
QJ
He
Bo
B
Yang
Su
S
Zeng
Yong-Zhou
YZ
Hu
Xiao-Xia
XX
Sheng
Jian-Qing
JQ
Gao
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D020442:Poloxamer / Q000737:chemistry*; D011312:Pressure; D011810:Quinoxalines / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D013535:Suspensions; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
C528740:3-(4-bromophenyl)-2-(ethylsulfonyl)-6-methylquinoxaline-1,4-dioxide; D000970:Antineoplastic Agents; D011810:Quinoxalines; D013501:Surface-Active Agents; D013535:Suspensions; D020442:Poloxamer
Antitumor; Nanosuspension; Poloxamer; Q39