Biotechnology and Drug Development Research Laboratory, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Sci Rep. 2020 May 7;10(1):7715. doi: 10.1038/s41598-020-64355-z.
Probucol (PB) is a drug that exhibits significant hydrophobicity and substantial intra and inter individual variability in oral absorption, with a miniature bioavailability and complex three compartmental pharmacokinetic modelling due to its high lipid affinity, low stability and high octanol to water partition coefficient. Multiple attempts to formulate PB have not produced satisfactory stable matrices, drug-release profile or rheological flow properties for optimum manufacturing conditions, and with positive and none toxic biological effects. Lithocholic acid (LCA) has recently shown to optimise formulation and cell uptake of drugs. Hence, the aim of this study was to design new PB delivery system, using LCA, and examine its morphology, rheology, stability, and cellular effects. PB was formulated with LCA and sodium alginate (PB-LCA-SA) using various microencapsulation methodologies, and best formulation was investigated in vitro and ex vivo. Using our Ionic Gelation Vibrational Jet flow technology, PB-LCA-SA microcapsules showed good stability and significantly enhanced cell viability, cellular respiration, and reduced inflammation suggesting potential LCA applications in PB delivery and biological effects.
普罗布考(PB)是一种具有显著疏水性和口服吸收个体内和个体间变异性的药物,由于其高亲脂性、低稳定性和高辛醇-水分配系数,生物利用度低,且具有复杂的三室药代动力学模型。尽管多次尝试对 PB 进行配方设计,但由于未能产生满意的稳定基质、药物释放特性或流变学流动特性,无法满足最佳生产条件,并且具有积极和无毒的生物学效应。最近,胆酸(LCA)已被证明可优化药物的配方和细胞摄取。因此,本研究旨在设计使用 LCA 的新型 PB 传递系统,并研究其形态、流变学、稳定性和细胞效应。使用各种微囊化方法将 PB 与胆酸钠(PB-LCA-SA)制成配方,并在体外和体内进行最佳配方的研究。使用我们的离子凝胶振动射流技术,PB-LCA-SA 微胶囊表现出良好的稳定性,显著提高了细胞活力、细胞呼吸作用,减少了炎症,这表明 LCA 在 PB 传递和生物学效应方面具有潜在的应用。