Enhancement of cellular uptake, transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation
文献类型：期刊论文
| 作者 | He, Yuan2; Xia, Deng-ning1; Li, Qiu-xia1,2; Tao, Jin-song1,3; Gan, Yong1 ; Wang, Chi2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2015-09 |
| 卷号 | 36期号:9页码:1151-1160 |
| 关键词 | saquinavir protease inhibitor nanocrystals Caco-2 cell monolayer intestinal mucosa pharmacokinetics |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2015.53 |
| 文献子类 | Article |
| 英文摘要 | Aim: Saquinavir (SQV) is the first protease inhibitor for the treatment of HIV infection, but with poor solubility. The aim of this study was to prepare a colloidal nanocrystal suspension for improving the oral absorption of SQV. Methods: SQV nanocrystals were prepared using anti-solvent precipitation-high pressure homogenization method. The nanocrystals were characterized by a Zetasizer and transmission electron microscopy (TEM). Their dissolution, cellular uptake and transport across the human colorectal adenocarcinoma cell line (Caco-2) monolayer were investigated. Bioimaging of ex vivo intestinal sections of rats was conducted with confocal laser scanning microscopy. Pharmacokinetic analysis was performed in rats administered nanocrystal SQV suspension (50 mg/kg, ig), and the plasma SQV concentrations were measured with HPLC. Results: The SQV nanocrystals were approximately 200 nm in diameter, with a uniform size distribution. The nanocrystals had a rod-like shape under TEM. The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals. The ex vivo intestinal section study revealed that the fluorescently labeled nanocrystals were located in the lamina propria and the epithelium of the duodenum and jejunum. Pharmacokinetic study showed that the maximal plasma concentration (C-max) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95-fold of that for coarse crystalline SQV suspension. Conclusion: The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir. |
| WOS关键词 | NITRENDIPINE NANOCRYSTALS ; P-GLYCOPROTEIN ; NANOPARTICLES ; BIOAVAILABILITY ; CELLS ; STABILITY ; DELIVERY ; DRUGS ; FATE |
| 资助项目 | National Natural Science Foundations of China[81202468] ; National Natural Science Foundations of China[81373356] ; China Postdoctoral Science Foundations[2013M530219] ; China Postdoctoral Science Foundations[2014T70445] ; Shanghai Science and Technology Innovation Action Plan for Basic Research[14JC1493200] ; SA-SIBS Scholarship Program[00000000] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5510642 |
| WOS记录号 | WOS:000360840200013 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276419]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Gan, Yong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Chongqing Med Univ, Sch Pharm, Chongqing 400016, Peoples R China; 3.Nanchang Univ, Coll Clin Med, Dept Pharm, Nanchang 330047, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Yuan,Xia, Deng-ning,Li, Qiu-xia,et al. Enhancement of cellular uptake, transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation[J]. ACTA PHARMACOLOGICA SINICA,2015,36(9):1151-1160. |
| APA | He, Yuan,Xia, Deng-ning,Li, Qiu-xia,Tao, Jin-song,Gan, Yong,&Wang, Chi.(2015).Enhancement of cellular uptake, transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation.ACTA PHARMACOLOGICA SINICA,36(9),1151-1160. |
| MLA | He, Yuan,et al."Enhancement of cellular uptake, transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation".ACTA PHARMACOLOGICA SINICA 36.9(2015):1151-1160. |
入库方式： OAI收割
来源：上海药物研究所
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