title: The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study.
abstract: In recent studies, we designed multi-compartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in an animal model of type 2 diabetes (T2D). Probucol (PB) is a highly lipophilic, antihyperlipidemic drug with potential antidiabetic effects. PB has low bioavailability and high inter-individual variations in absorption, which limits its clinical applications. In a new study, the bile acid, taurocholic acid (TCA), exerted permeation enhancing effects in vivo. Accordingly, this study aimed to design and characterize TCA-based PB microcapsules and examine the effects of TCA on the microcapsules' morphology, stability, and release profiles. Microcapsules were prepared using the polymer sodium alginate (SA). Two types of microcapsules were produced, one without TCA (PB-SA, control) and one with TCA (PB-TCA-SA, test). Microcapsules were studied in terms of morphology, surface structure and composition, size, drug contents, cross-sectional imaging (using microtomography (Micro-CT) analysis), Zeta potential, thermal and chemical profiles, rheological parameters, swelling, mechanical strength, and release studies at various temperature and pH values. The production yield and the encapsulation efficiency were also studied together with in vitro efficacy testing of cell viability at various glucose concentrations and insulin and TNF-α production using clonal-mouse pancreatic β-cells. PB-TCA-SA microcapsules showed uniform structure and even distribution of TCA within the microcapsules. Drug contents, Zeta potential, size, rheological parameters, production yield, and the microencapsulation efficiency remained similar after TCA addition. In vitro testing showed PB-TCA-SA microcapsules improved β-cell survival under hyperglycemic states and reduced the pro-inflammatory cytokine TNF-α while increasing insulin secretions compared with PB-SA microcapsules. PB-TCA-SA microcapsules also showed good stability, better mechanical (p < 0.01) and swelling (p < 0.01) characteristics, and optimized controlled release at pH 7.8 (p < 0.01) compared with control, suggesting desirable targeted release properties and potential applications in the oral delivery of PB in T2D.
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, GPO Box U1987, Perth, Western Australia, 6845, Australia.
authors.forename: Armin
authors.initials: A
authors.lastname: Mooranian
authors.forename: Rebecca
authors.initials: R
authors.lastname: Negrulj
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.forename: Hani
authors.initials: H
authors.lastname: Al-Salami
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003920:Diabetes Mellitus; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011341:Probucol / Q000008:administration & dosage* / Q000737:chemistry; D013656:Taurocholic Acid / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D013656:Taurocholic Acid; D011341:Probucol