title: Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic β-cell line.
abstract: BACKGROUND
  We have shown that the primary bile acid, cholic acid (CA), has anti-diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D).
  
  
  OBJECTIVE
  This study aimed to encapsulate CA with PB and examine the formulation and surface characteristics of the microcapsules. We also tested the microcapsules' biological effects on pancreatic β-cells.
  
  
  METHODS
  Using the polymer, sodium alginate (SA), two formulations were prepared: PB-SA (control), and PB-CA-SA (test). Complete characterizations of the morphology, shape, size, chemical, thermal, and rheological properties, swelling and mechanical strength, cross-sectional imaging (Micro CT), stability, Zeta-potential, drug contents, and PB release profile were carried out, at different temperature and pH values. The microcapsules were applied to a NIT-1 cell culture and the supernatant was analyzed for insulin and TNF-α concentrations.
  
  
  RESULTS
  CA incorporation optimized the PB microcapsules, which exhibited pseudoplastic-thixotropic rheological characteristics. The size of the microcapsules remained similar after CA addition, and the microcapsules showed even drug distribution and no chemical alterations of the excipients. Micro-CT imaging, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy showed consistent microcapsules with uniform shape and morphology. PB-CA-SA microcapsules enhanced NIT-1 cell viability under hyperglycemic states and resulted in improved insulin release as well as reduced cytokine production at the physiological glucose levels.
  
  
  CONCLUSIONS
  The addition of the primary bile acid, CA, improved the physical properties of the microcapsules and enhanced their pharmacological activity in vitro, suggesting potential applications in diabetes treatment.
authors.affiliation: a Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University , Perth, Western Australia, Australia.
authors.forename: Armin
authors.initials: A
authors.lastname: Mooranian
authors.affiliation: a Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University , Perth, Western Australia, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Negrulj
authors.affiliation: b Stem Cell and Cancer Biology Laboratory, School of Biomedical Science, Curtin Health Innovation Research Institute, Curtin University , Perth Western Australia, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.affiliation: a Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University , Perth, Western Australia, Australia.
authors.forename: Hani
authors.initials: H
authors.lastname: Al-Salami
mesh_terms: D000818:Animals; D002214:Capsules; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011341:Probucol / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002214:Capsules; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D011341:Probucol
keywords: NIT-1 β-cells; artificial-cell microencapsulation; bile acids; diabetes mellitus; inflammation; probucol