Mesoporous Silica Nanoparticles for Increasing the Oral Bioavailability and Permeation of Poorly Water Soluble Drugs
详细信息 查看全文
- 作者：Yanzhuo Zhang ; Jiancheng Wang ; Xiaoyu Bai ; Tongying Jiang ; Qiang Zhang ; Siling Wang
- 刊名：Molecular Pharmaceutics
- 出版年：2012
- 出版时间：March 5, 2012
- 年：2012
- 卷：9
- 期：3
- 页码：505-513
- 全文大小：543K
- 年卷期：v.9,no.3(March 5, 2012)
- ISSN：1543-8392
文摘
We investigate the effects of spherical mesoporous silica nanoparticles (MSNs) as an oral drug delivery system to improve the oral bioavailability of the model drug telmisartan (TEL) and examine their cellular uptake and cytotoxicity. Further, we explore the mechanisms behind the improved oral absorption of poorly soluble drugs promoted by MSNs. An investigation of intestinal epithelial cellular binding, association and uptake was carried out by laser scanning confocal microscopy, transmission electron microscopy and fluorescence activated cell sorting. The results show that the cellular uptake is highly time-, concentration- and size-dependent. The model drug permeability studies in the human colon carcinoma (Caco-2) cell lines indicated that MSNs could significantly enhance TEL permeability and reduce rate of drug efflux. After loading TEL into MSNs, its oral bioavailability was compared with that of the marketed product Micardis and TEL-loaded ordered mesoporous silica microparticles (MSMs) in beagle dogs. The relative bioavailability of TEL-loaded MSN formulation and TEL-loaded MSM formulation was 154.4 卤 28.4% and 129.1 卤 15.6%, respectively. MSNs offer the potential to achieve enhanced oral bioavailability of poorly soluble drugs via improved drug dissolution rate and enhanced drug permeability.