Chenodeoxycholic Acid Pharmacology in Biotechnology and Transplantable Pharmaceutical Applications for Tissue Delivery: An Acute Preclinical Study
Armin Mooranian,
Corina Mihaela Ionescu,
Susbin Raj Wagle,
Bozica Kovacevic,
Daniel Walker,
Melissa Jones,
Jacqueline Chester,
Edan Johnston,
Maja Danic,
Momir Mikov,
Crispin Dass,
Hani Al-Salami
Affiliations
Armin Mooranian
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Corina Mihaela Ionescu
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Susbin Raj Wagle
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Bozica Kovacevic
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Daniel Walker
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Melissa Jones
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Jacqueline Chester
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Edan Johnston
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Maja Danic
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21101 Novi Sad, Serbia
Momir Mikov
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21101 Novi Sad, Serbia
Crispin Dass
Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Hani Al-Salami
Biotechnology and Drug Development Research Laboratory, Curtin Medical School, Health Innovation Research Institute, Curtin University, Perth 6102, Australia
Introduction. Primary bile acids (PBAs) are produced and released into human gut as a result of cholesterol catabolism in the liver. A predominant PBA is chenodeoxycholic acid (CDCA), which in a recent study in our laboratory, showed significant excipient-stabilizing effects on microcapsules carrying insulinoma β-cells, in vitro, resulting in improved cell functions and insulin release, in the hyperglycemic state. Hence, this study aimed to investigate the applications of CDCA in bio-encapsulation and transplantation of primary healthy viable islets, preclinically, in type 1 diabetes. Methods. Healthy islets were harvested from balb/c mice, encapsulated in CDCA microcapsules, and transplanted into the epididymal tissues of 6 syngeneic diabetic mice, post diabetes confirmation. Pre-transplantation, the microcapsules’ morphology, size, CDCA-deep layer distribution, and physical features such as swelling ratio and mechanical strength were analyzed. Post-transplantation, animals’ weight, bile acids’, and proinflammatory biomarkers’ concentrations were analyzed. The control group was diabetic mice that were transplanted encapsulated islets (without PBA). Results and Conclusion. Islet encapsulation by PBA microcapsules did not compromise the microcapsules’ morphology or features. Furthermore, the PBA-graft performed better in terms of glycemic control and resulted in modulation of the bile acid profile in the brain. This is suggestive that the improved glycemic control was mediated via brain-related effects. However, the improvement in graft insulin delivery and glycemic control was short-term.
