Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki, FI-00014, Finland.
Biomaterials. 2012 Apr;33(11):3353-62. doi: 10.1016/j.biomaterials.2012.01.029. Epub 2012 Jan 29.
Impediments to intestinal absorption, such as poor solubility and instability in the variable conditions of the gastrointestinal (GI) tract plague many of the current drugs restricting their oral bioavailability. Particulate drug delivery systems hold great promise in solving these problems, but their effectiveness might be limited by their often rapid transit through the GI tract. Here we describe a bioadhesive oral drug delivery system based on thermally-hydrocarbonized porous silicon (THCPSi) functionalized with a self-assembled amphiphilic protein coating consisting of a class II hydrophobin (HFBII) from Trichoderma reesei. The HFBII-THCPSi nanoparticles were found to be non-cytotoxic and mucoadhesive in AGS cells, prompting their use in a biodistribution study in rats after oral administration. The passage of HFBII-THCPSi nanoparticles in the rat GI tract was significantly slower than that of uncoated THCPSi, and the nanoparticles were retained in stomach by gastric mucoadhesion up to 3 h after administration. Upon entry to the small intestine, the mucoadhesive properties were lost, resulting in the rapid transit of the nanoparticles through the remainder of the GI tract. The gastroretentive drug delivery system with a dual function presented here is a viable alternative for improving drug bioavailability in the oral route.
肠道吸收的障碍，如在胃肠道（GI）多变条件下的差溶解性和不稳定性，困扰着许多当前的药物，限制了它们的口服生物利用度。颗粒药物传递系统在解决这些问题方面具有巨大的潜力，但它们的效果可能受到其在 GI 道中快速通过的限制。在这里，我们描述了一种基于热烃化多孔硅（THCPSi）的生物粘附口服药物传递系统，该系统用由里氏木霉（Trichoderma reesei）的 II 类疏水蛋白（HFBII）自组装的两亲性蛋白涂层进行功能化。发现 HFBII-THCPSi 纳米颗粒在 AGS 细胞中无细胞毒性和粘膜粘附性，这促使我们在大鼠口服给药后进行生物分布研究。与未涂层的 THCPSi 相比，HFBII-THCPSi 纳米颗粒在大鼠 GI 道中的通过速度明显较慢，并且纳米颗粒通过胃粘膜粘附在胃中保留长达 3 小时。进入小肠后，失去了粘膜粘附性，导致纳米颗粒在 GI 道的其余部分快速通过。这里提出的具有双重功能的胃滞留药物传递系统是改善口服途径药物生物利用度的可行替代方案。
