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

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

Inflammatory bowel disease: clinical aspects and treatments

Inflammatory bowel disease (IBD) is defined as a chronic intestinal inflammation that results from host-microbial interactions in a genetically susceptible individual. IBDs are a group of autoimmune diseases that are characterized by inflammation of both the small and large intestine, in which elements of the digestive system are attacked by the body's own immune system. This inflammatory condition encompasses two major forms, known as Crohn's disease and ulcerative colitis. Patients affected by these diseases experience abdominal symptoms, including diarrhea, abdominal pain, bloody stools, and vomiting. Moreover, defects in intestinal epithelial barrier function have been observed in a number of patients affected by IBD. In this review, we first describe the types and symptoms of IBD and investigate the role that the epithelial barrier plays in the pathophysiology of IBD as well as the major cytokines involved. We then discuss steps used to diagnose this disease and the treatment options available, and finally provide an overview of the recent research that aims to develop new therapies for such chronic disorders

An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid) as a permeation enhancer

The authors have previously designed, developed, and characterized a novel microencapsulated formulation as a platform for the targeted delivery of therapeutics in an animal model of type 2 diabetes, using the drug probucol (PB). The aim of this study was to optimize PB microcapsules by incorporating the bile acid deoxycholic acid (DCA), which has good permeation-enhancing properties, and to examine its effect on microcapsules’ morphology, rheology, structural and surface characteristics, and excipients’ chemical and thermal compatibilities. Microencapsulation was carried out using a BÜCHI-based microencapsulating system established in the authors’ laboratory. Using the polymer sodium alginate (SA), two microencapsulated formulations were prepared: PB-SA (control) and PB-DCA-SA (test) at a constant ratio (1:30 and 1:3:30, respectively). Complete characterization of the microcapsules was carried out. The incorporation of DCA resulted in better structural and surface characteristics, uniform morphology, and stable chemical and thermal profiles, while size and rheological parameters remained similar to control. In addition, PB-DCA-SA microcapsules showed good excipients’ compatibilities, which were supported by data from differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray studies, suggesting microcapsule stability. Hence, PB-DCA-SA microcapsules have good rheological and compatibility characteristics and may be suitable for the oral delivery of PB in type 2 diabetes

Novel artificial cell microencapsulation of a complex gliclazide-deoxycholic bile acid formulation: A Characterization Study

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

Microencapsulation as a novel delivery method for the potential antidiabetic drug, Probucol

Introduction: In previous studies, we successfully designed complex multicompartmental microcapsules as a platform for the oral targeted delivery of lipophilic drugs in type 2 diabetes (T2D). Probucol (PB) is an antihyperlipidemic and antioxidant drug with the potential to show benefits in T2D. We aimed to create a novel microencapsulated formulation of PB and to examine the shape, size, and chemical, thermal, and rheological properties of these microcapsules in vitro. Method: Microencapsulation was carried out using the Büchi-based microencapsulating system developed in our laboratory. Using the polymer, sodium alginate (SA), empty (control, SA) and loaded (test, PB-SA) microcapsules were prepared at a constant ratio (1:30). Complete characterizations of microcapsules, in terms of morphology, thermal profiles, dispersity, and spectral studies, were carried out in triplicate. Results: PB-SA microcapsules displayed uniform and homogeneous characteristics with an average diameter of 1 mm. The microcapsules exhibited pseudoplastic-thixotropic characteristics and showed no chemical interactions between the ingredients. These data were further supported by differential scanning calorimetric analysis and Fourier transform infrared spectral studies, suggesting microcapsule stability. Conclusion: The new PB-SA microcapsules have good structural properties and may be suitable for the oral delivery of PB in T2D. Further studies are required to examine the clinical efficacy and safety of PB in T2D

Probucol Release from Novel Multicompartmental Microcapsules for the Oral Targeted Delivery in Type 2 Diabetes

In previous studies, we developed and characterised multicompartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in type 2 diabetes (T2D). We also designed a new microencapsulated formulation of probucol-sodium alginate (PB-SA), with good structural properties and excipient compatibility. The aim of this study was to examine the stability and pH-dependent targeted release of the microcapsules at various pH values and different temperatures. Microencapsulation was carried out using a Büchi-based microencapsulating system developed in our laboratory. Using SA polymer, two formulations were prepared: empty SA microcapsules (SA, control) and loaded SA microcapsules (PB-SA, test), at a constant ratio (1:30), respectively. Microcapsules were examined for drug content, zeta potential, size, morphology and swelling characteristics and PB release characteristics at pH 1.5, 3, 6 and 7.8. The production yield and microencapsulation efficiency were also determined. PB-SA microcapsules had 2.6 ± 0.25% PB content, and zeta potential of −66 ± 1.6%, suggesting good stability. They showed spherical and uniform morphology and significantly higher swelling at pH 7.8 at both 25 and 37°C (p < 0.05). The microcapsules showed multiphasic release properties at pH 7.8. The production yield and microencapsulation efficiency were high (85 ± 5 and 92 ± 2%, respectively). The PB-SA microcapsules exhibited distal gastrointestinal tract targeted delivery with a multiphasic release pattern and with good stability and uniformity. However, the release of PB from the microcapsules was not controlled, suggesting uneven distribution of the drug within the microcapsules

Stability and Release Kinetics of an Advanced Gliclazide-Cholic Acid Formulation: The Use of Artificial-Cell Microencapsulation in Slow Release Targeted Oral Delivery of Antidiabetics

Introduction: In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures. Method: Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C. Results: The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8, p < 0.01). Conclusion: The new formulation exhibits colon-targeted delivery and the addition of CA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and CA to the lower intestine

The impact of allylamine-bile acid combinations on cell delivery microcapsules in diabetes

© 2016 Informa UK Limited, trading as Taylor & Francis Group. Objective: In a recent study, we developed a new microencapsulating method for ß-cell microencapsulation, but cell viability declined rapidly, post microencapsulation, due to potential polymer-polyelectrolyte chelation and non-porous microcapsules’ membranes resulting in cell apoptosis. Thus, this study tested the effects of incorporating cationic polyamine at 1% w/v, on microcapsule strength and cell viability, in the absence or presence of an anionic tertiary bile acid (ATBA) with potential cell-protective effects. Methods: 1% w/v polyamine was used without or with ATBA, to form ß-cell microcapsules and physical and biological analyses was carried out 50?h post microencapsulation. Results: Microcapsules containing 1% w/v polyamine showed weak physical properties and low cell viability and ATBA incorporation resulted in &gt;30% reduction in cell viability and increased levels of pro-inflammatory cytokines. Conclusion: Neither 1% w/v polyamine nor the presence of ATBA resulted in optimised cell viability, but rather reduced cell viability, enhanced inflammation and lowered insulin secretion

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

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

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