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, Banaszak Holl Mark M, Zhang Qiang
Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China; School of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
Nanomedicine. 2015 Jul;11(5):1141-51. doi: 10.1016/j.nano.2015.02.011. Epub 2015 Mar 16.
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-NH2 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigated in vitro using 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-NH2 molecular 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-NH2 molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery.
Various 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.
本研究比较了树枝状聚合物和脂质体制剂对辛伐他汀（SMV）的水溶性、跨上皮转运及口服生物利用度的影响。选用胺基封端的G5聚酰胺-胺型树枝状聚合物（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细胞单层体外研究这些制剂对跨上皮转运的影响。结果表明，两种制剂均显著提高了SMV的溶解度和跨上皮转运。大鼠体内药代动力学研究还显示，SMV/G5-NH2分子复合物和SMV脂质体均显著提高了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源于脂质体对SMV更好的增溶和包封以及更有效的细胞内SMV递送。
已设计出各种载体系统以增强口服途径的药物递送。在本研究中，作者比较了G5聚酰胺-胺型树枝状聚合物和脂质体制剂在这种水溶性差的药物的溶解度、跨上皮转运及口服生物利用度方面的差异。这种认识增进了我们对药物载体系统进一步开发的了解。
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