title: Novel artificial cell microencapsulation of a complex gliclazide-deoxycholic bile acid formulation: a characterization study.
abstract: Gliclazide (G) is an antidiabetic drug commonly used in type 2 diabetes. It has extrapancreatic hypoglycemic effects, which makes it a good candidate in type 1 diabetes (T1D). In previous studies, we have shown that a gliclazide-bile acid mixture exerted a hypoglycemic effect in a rat model of T1D. We have also shown that a gliclazide-deoxycholic acid (G-DCA) mixture resulted in better G permeation in vivo, but did not produce a hypoglycemic effect. In this study, we aimed to develop a novel microencapsulated formulation of G-DCA with uniform structure, which has the potential to enhance G pharmacokinetic and pharmacodynamic effects in our rat model of T1D. We also aimed to examine the effect that DCA will have when formulated with our new G microcapsules, in terms of morphology, structure, and excipients' compatibility. Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) at a ratio of 1:30, and G-DCA-SA (test) at a ratio of 1:3:30. Complete characterization of microcapsules was carried out. The new G-DCA-SA formulation was further optimized by the addition of DCA, exhibiting pseudoplastic-thixotropic rheological characteristics. The size of microcapsules remained similar after DCA addition, and these microcapsules showed no chemical interactions between the excipients. This was supported further by the spectral and microscopy studies, suggesting microcapsule stability. The new microencapsulated formulation has good structural properties and may be useful for the oral delivery of G in T1D.
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA, Australia.
authors.forename: Armin
authors.initials: A
authors.lastname: Mooranian
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Negrulj
authors.affiliation: Faculty of Science and Engineering, Curtin University, Perth, WA, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Chen-Tan
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Hesham S
authors.initials: HS
authors.lastname: Al-Sallami
authors.affiliation: School of Public Health, Curtin University, Perth, WA, Australia.
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, WA, Australia.
authors.forename: Trilochan
authors.initials: T
authors.lastname: Mukkur
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia ; Department of Pharmacy, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro.
authors.forename: Momir
authors.initials: M
authors.lastname: Mikov
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia ; Department of Pharmacy, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Golocorbin-Kon
authors.affiliation: Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Fakhoury
authors.affiliation: Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, WA, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.affiliation: Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA, Australia.
authors.forename: Hani
authors.initials: H
authors.lastname: Al-Salami
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D058045:Artificial Cells / Q000737:chemistry*; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003840:Deoxycholic Acid / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D005079:Excipients / Q000737:chemistry; D005907:Gliclazide / Q000008:administration & dosage* / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D012212:Rheology
chemical_list: D000464:Alginates; D002214:Capsules; D005079:Excipients; D006603:Hexuronic Acids; D007004:Hypoglycemic Agents; D003840:Deoxycholic Acid; D020723:Glucuronic Acid; D005907:Gliclazide
keywords: bile acids; gliclazide; polymer; type 2 diabetes
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