G5 PAMAM dendrimer versus liposome: A comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin
G5 PAMAM dendrimer versus liposome: A comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin
复制标题
G5 PAMAM树枝状聚合物与脂质体：辛伐他汀体外跨上皮转运和体内口服吸收的比较研究
DOI：
10.1016/j.nano.2015.02.011
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发表时间：
2015
影响因子：
5.4
通讯作者：
Zhang Qiang
中科院分区：
文献类型：
--
作者：
Qi Rong;Zhang Heran;Xu Lu;Shen Wenwen;Chen Cong;Wang Chao;Cao Yini;Wang Yunan;van Dongen Mallory A.;He Bing;Wang Siling;Liu George;Holl Mark M. Banaszak;Zhang Qiang
本研究比较了树枝状聚合物和脂质体制剂对辛伐他汀 (SMV) 水溶性、跨上皮转运和口服生物利用度的影响。选择端氨基G5 PAMAM树枝状大分子(G5-NH2)形成SMV/G5-NH2分子复合物，并采用薄膜分散法制备SMV脂质体。使用 Caco-2 单层细胞在体外研究了这些制剂对跨上皮转运的影响。结果表明，两种制剂均显着改善了 SMV 的溶解度和跨上皮转运。大鼠药代动力学研究还表明，SMV/G5-NH2 分子复合物和 SMV-脂质体均显着提高了 SMV 的口服生物利用度，其中脂质体比 G5-NH2 更有效。与 SMV/G5-NH2 分子复合物相比，SMV-脂质体总体上更好的口服吸收似乎是由于 SMV 更好的脂质体溶解和封装以及更有效的细胞内 SMV 递送。 来自临床编辑的各种载体系统已设计用于增强通过口服途径的药物递送。在这项研究中，作者将 G5 PAMAM 树枝状聚合物与脂质体制剂在溶解度、跨上皮转运和这种水溶性差的药物的口服生物利用度方面进行了比较。这种理解提高了我们对药物载体系统进一步开发的认识。
This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigatedin vitrousing Caco-2 cell monolayers. Results indicated that the solubility and transepithelial transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G5-NH2molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery.From the Clinical EditorVarious carrier systems have been designed to enhance drug delivery via the oral route. In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug. This understanding has improved our knowledge in the further development of drug carrier systems.