Optimization of epirubicin nanoparticles using experimental design for enhanced intravesical drug delivery

被引：63
作者：
Chang, Li-Ching [2 ]
Wu, Shu-Chin [1 ]
Tsai, Jen-Wei [3 ]
Yu, Tsan-Jung [4 ]
Tsai, Tong-Rong [1 ]
机构：
[1] Kaohsiung Med Univ, Fac Pharm, Kaohsiung 807, Taiwan
[2] I Shou Univ, Dept Occupat Therapy, Kaohsiung, Taiwan
[3] E Da Hosp, Dept Pathol, Kaohsiung, Taiwan
[4] I Shou Univ, E DA Hosp, Dept Urol, Kaohsiung, Taiwan
来源：
INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2009年 / 376卷 / 1-2期
关键词：
Epirubicin; Nanoparticles; Bladder cancer; Intravesical instillation; SUPERFICIAL BLADDER-CANCER; PHARMACOTHERAPY;
D O I：
10.1016/j.ijpharm.2009.04.045
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The aim of this study was to develop poly(ethyl-2-cyanoacrylate) (PECA) epirubicin-loaded nanoparticles (EPI-NP). A 2(3) factorial design was adopted with the type of surfactant, surfactant concentration and the pH of the polymerization medium as independent variables. The particle size, entrapment efficacy and polydispersity index of eight formulations were then evaluated. Two optimal EPI-NP formulations, 2% Tween 80 EPI-NP (TW80 EPI-NP) and 0.5% pluronic F68 EPI-NP (1768 EPI-NP) at pH 2.5 were developed. The sizes of TW80 EPI-NP and F68 EPI-NP at maximum intensity were 90 and 220 nm, respectively. Both TW80 EPI-NP and F68 EPI-NP showed potent cytotoxicity against human bladder cancer T24 and RT4 cells, compared with aqueous solutions of epirubicin (EPI-AQ). The penetration and accumulation of EPI-NPs in pig urothelium were studied by tissue concentration-depth profiles and fluorescence microscopy. The cumulative amounts of epirubicin following EPI-AQ, TW80 EPI-NP and F68 EPI-NP treatments were 842.48 +/- 24.66, 1314.66 +/- 33.07 and 595.21 +/- 24.16 mu g, respectively. The current study showed the successful development of urothelium adhesive and penetrative PECA EPI-NPs. This has potential for the in vivo application of epirubicin-loaded nanoparticles for intravesical instillation in bladder cancer therapy. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码：195 / 203
页数：9
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