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Maximizing the Oral Bioavailability of Poorly Water-Soluble Drugs Using Novel Oil-Like Materials in Lipid-Based Formulations
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2021-08-05 , DOI: 10.1021/acs.molpharmaceut.1c00197
Saed Abbasi 1 , Haruki Higashino 2 , Yusuke Sato 3 , Keiko Minami 2 , Makoto Kataoka 2 , Shinji Yamashita 2 , Hideyoshi Harashima 3
Affiliation  

Lipid-based formulations, such as self-microemulsifying drug-delivery systems (SMEDDSs), are promising tools for the oral delivery of poorly water-soluble drugs. However, failure to maintain adequate aqueous solubility after coming into contact with gastrointestinal fluids is a major drawback. In this study, we examined the use of a novel cinnamic acid-derived oil-like material (CAOM) that binds drugs with a high affinity through π–π stacking and hydrophobic interactions, as an oil core in a SMEDDS for the oral delivery of fenofibrate in rats. The use of the CAOM in the SMEDDS resulted in an unprecedented enhancement in fenofibrate bioavailability, which exceeded the bioavailability values obtained using SMEDDSs based on corn oil, a conventional triglyceride oil, or Labrasol, an enhancer of intestinal permeation. Further characterization revealed that the CAOM SMEDDS does not alter the intestinal permeability and has no inhibitory activity on P-glycoprotein-mediated drug efflux. The results reported herein demonstrate the strong potential of CAOM formulations as new solubilizers for the efficient and safe oral delivery of drugs that have limited water solubility.

中文翻译:

在脂质基制剂中使用新型油状材料最大限度地提高水溶性差的药物的口服生物利用度

基于脂质的制剂,例如自微乳化药物递送系统 (SMEDDS),是用于口服递送水溶性差的药物的有前途的工具。然而,在与胃肠液接触后未能保持足够的水溶性是主要缺点。在这项研究中,我们研究了一种新型肉桂酸衍生油状材料 (CAOM),该材料通过 π-π 堆积和疏水相互作用以高亲和力结合药物,作为 SMEDDS 中的油核,用于口服给药非诺贝特在大鼠中。在 SMEDDS 中使用 CAOM 导致非诺贝特生物利用度前所未有的提高,超过了使用基于玉米油、传统甘油三酯油或 Labrasol(一种肠道渗透增强剂)的 SMEDDS 获得的生物利用度值。进一步的表征表明,CAOM SMEDDS 不会改变肠道通透性,并且对 P-糖蛋白介导的药物流出没有抑制活性。本文报道的结果证明了 CAOM 制剂作为新型增溶剂的强大潜力,可用于有效和安全地口服递送水溶性有限的药物。
更新日期:2021-09-06
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