Potentials and Limitations of Bile Acids in Type 2 Diabetes Mellitus: Applications of Microencapsulation as a Novel Oral Delivery System

Abstract

Type 2 diabetes (T2D) is a chronic metabolic disorder resulting from genetic and environmental factors that bring about tissue desensitization to insulin and consequent hyperglycemia. Despite strict glycemic control and the fact that new and more effective antidiabetic drugs are continuously appearing on the market, diabetic patients still suffer from the disease and its complications. Recent findings present a strong link between diabetes, inflammation, altered gut microbiota and bile acid (BA) disturbances. BAs are naturally produced in humans and are gaining an appreciable interest as an adjunct treatment for T2D due to their endocrine signalling and anti-inflammatory properties. However a significant limitation to their efficacy is their low oral absorption, poor targeted delivery, gut metabolism and inter-and intra-individual dose variations. Thus there is a need for a novel and robust formulation that will encapsulate the BAs and protect them until they reach the lower intestine allowing them to be clinically beneficial. Artificial Cell Microencapsulation (ACM) is a novel oral delivery system for biologically active molecules and has been used significantly in the delivery of various cells and therapeutics. ACM-BA formulation has the potential to optimise BA efficacy and safety profiles and may have a place in the treatment of diabetes. This review aims to investigate the applications of BAs in T2D and the use of ACM as a novel delivery system for their optimum delivery.

Pharmacological and Biological Study of Microencapsulated Probucol-Secondary Bile Acid in a Diseased Mouse Model

“…SA is a biodegradable polymer that protects the drug, and its physicochemical properties are impacted by gastrointestinal pH values [ 19 , 61 ]. The pH values examined were chosen based on previous studies conducted in our lab, which typically reflect the distal segment of the small intestine from where the absorption of the antidiabetic drug, either alone or together with bile acids, should occur [ 22 , 44 , 62 ]. The membrane-stabilising studies showed microcapsules had increased swelling properties in higher pH values for both formulations indicating that SA undergoes extensive swelling at high pH due to higher water uptake caused by increasing its porosity, water infiltration, and solubilisation of the polymer [ 63 ].…”

“…Bile acids primary function is to support solubilisation and digestion of lipids. Recently they have been shown to improve oral drug delivery as absorption and permeation-enhancing agents as well as improving drug stability [ 20 , 21 , 22 ]. The secondary bile acid lithocholic acid (LCA) has shown anti-inflammatory and formulation-stabilising effects in atherosclerosis [ 23 ].…”

Artificial Cell Encapsulation for Biomaterials and Tissue Bio-Nanoengineering: History, Achievements, Limitations, and Future Work for Potential Clinical Applications and Transplantation

“…The VNM uses vibration, causing a breakup of laminar liquid, which, resulting from frequency selection, causes equally sized droplets where the higher the frequency, the smaller the produced microcapsules [50,98,120]. The spherical droplets are formed as a direct result of surface tension [50,120].…”

“…The VNM uses vibration, causing a breakup of laminar liquid, which, resulting from frequency selection, causes equally sized droplets where the higher the frequency, the smaller the produced microcapsules [50,98,120]. The spherical droplets are formed as a direct result of surface tension [50,120]. The VNM technique also utilises a range of other parameters aside from vibration frequency, including nozzle size, electrode tension and jet flow rate to result in droplet formation [96,98,[121][122][123][124].…”

“…This occurs unless the underlying causes of bile acid disturbances, inflammation and dysbiosis, are addressed [48,49]. A review by Negrulj et al, focused on the potential applications of bile acids as a treatment modality in the management of T2D using the novel advanced drug delivery platform of Artificial Cell Microencapsulation (ACM) via the Vibrating Nozzle Method (VNM), and may be of particular interest to the reader [50]. The concept of ACM is described as the development of a semipermeable microcapsule, described in 1964 by Thomas Chang [51,52].…”