Preparation and evaluation of N3-O-toluyl-fluorouracil-loaded liposomes
Preparation and evaluation of N3-O-toluyl-fluorouracil-loaded liposomes
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DOI：
10.1016/j.ijpharm.2007.11.017
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发表时间：
2008-04-02
影响因子：
5.8
通讯作者：
Xu, Wenfang
中科院分区：
文献类型：
--
作者：
Sun, Weitong;Zhang, Na;Xu, Wenfang
本研究的目的是开发一种新的和潜在的抗肿瘤亲脂性前药5-氟尿嘧啶（5-FU）-N-3-O-甲苯甲酰-氟尿嘧啶（TFu）的脂质体给药系统，旨在提高口服和静脉给药5-FU的生物利用度和治疗效果。采用改进的薄膜分散-均质法制备了TFu脂质体，并以包封率为指标对处方和工艺参数进行了优化。分别从粒径、粒径分布、Zeta电位、包封率、载药量和物理稳定性等方面对载TFu脂质体进行表征。同时考察了其体外释药特性、体内药代动力学特性和生物利用度。发现配制的脂质体的尺寸相对均匀（400.5 +/-9.6nm），具有负ζ电位（-6.4 +/-0.8mV）。包封率和载药量分别为88.87 ± 3.25%和8.89 ± 0.19%。物理稳定性实验结果表明，冻干的载TFu脂质体在4 ℃下至少稳定9个月。载TFu脂质体的体外释药符合双指数方程。小鼠体内药动学研究结果表明，脂质体口服给药后的生物利用度高于混悬液，静脉注射给药后与50%乙醇溶液生物等效。局这些结果表明，载TFu脂质体作为口服或静脉给药的实用制剂是有价值的。(c)2007 Elsevier B. V.保留所有权利。
This study was aimed at developing a liposome delivery system for a new and potential antitumor lipophilic prodrug of 5-fluorouracil (5-FU)-N-3-O-toluyl-fluorouracil (TFu), intended to improve the bioavailability and therapeutic efficacy of 5-Fu by oral and intravenous administration. TFu-loaded liposomes were prepared by a modified film dispersion-homogenization technique, the formulation and manufacture parameters were optimized concerning the drug encapsulation efficiency. TFu-loaded liposomes were characterized according to particle size, size distribution, zeta potential, drug entrapment efficiency, drug loading and physical stability, respectively. In vitro release characteristics, in vivo pharmacokinetic properties and bioavailabilities were also investigated. The formulated liposomes were found to be relatively uniform in size (400.5 +/- 9.6 nm) with a negative zeta potential (-6.4 +/- 0.8 mV). The drug entrapment efficiency and loading were (88.87 +/- 3.25%) and (8.89 +/- 0.19%), respectively. The physical stability experiments results indicated that lyophilized TFu-loaded liposomes were stable for at least 9 months at 4 degrees C. In vitro drug release profile of TFu-loaded liposomes followed the bi-exponential equation. The results of the pharmacokinetic studies in mice indicated that the bioavailability of TFu-loaded liposomes was higher than the suspension after oral administration, and was bioequivalent comparing with TFu 50% alcohol solution after intravenous (i.v.) administration. These results indicated that TFu-loaded liposomes were valued to develop as a practical preparation for oral or i.v. administration. (c) 2007 Elsevier B.V. All rights reserved.