Polyelectrolytes Formulated with Primary Unconjugated Bile Acid Optimised Pharmacology of Bio-Engineered Implant

Author:

Mooranian Armin,Ionescu Corina MihaelaORCID,Wagle Susbin RajORCID,Kovacevic BozicaORCID,Walker DanielORCID,Jones MelissaORCID,Chester JacquelineORCID,Foster Thomas,Johnston Edan,Kojic SanjaORCID,Stojanovic GoranORCID,Mikov Momir,Al-Salami HaniORCID

Abstract

Introduction. Several studies have shown that different biomaterials and hydrogels comprising various bile acids such as chenodeoxycholic acid (CDCA), as well as excipients such as poly-(styrene)-sulphonate (PSS) and poly-(allyl)-amine (PAA), exhibited positive biological effects on encapsulated viable pancreatic β-cells. Hence, this study aimed to investigate whether incorporating CDCA with PSS and PAA will optimise the functions of encapsulated pancreatic islets post-transplantation in Type 1 diabetes (T1D). Methods. Mice were made T1D, divided into two equal groups, and transplanted with encapsulated islets in PSS-PAA (control) or with CDCA-PSS-PAA (treatment) microcapsules. The effects of transplanted microcapsules on blood glucose, inflammation and the bile acid profile were measured post-transplantation. Results and Conclusion. Compared with control, the treatment group showed better survival rate, improved glycaemic control, and lower inflammatory profile, illustrated by ↓ interleukin 1-β, interleukin-6, interleukin-12, and tumour-necrosis factor-α, and ↓ levels of the bile acid, as well as lithocholic acid in the plasma, liver, large intestine and faeces. The results suggest that CDCA incorporation with PSS-PAA microcapsules exerted beneficial effects on encapsulated islets and resulted in enhanced diabetes treatment, post-transplantation, at the local and systemic levels.

Funder

European Union Horizon 2020 research project and innovation program under the Marie Skłodowska-Curie Grant

Publisher

MDPI AG

Subject

Pharmaceutical Science

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