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

The effects of Ionic Gelation- Vibrational Jet Flow technique in fabrication of microcapsules incorporating ß-cell: applications in Type-1 Diabetes

BACKGROUND: In recent studies, we have incorporated bile acid and polyelectrolytes into pancreatic ß-cell microcapsules and examined their cell viability and microcapsule morphology. Cell viability remained low post microencapsulation mainly due to cell leakage. OBJECTIVE: This study aimed to incorporate 3 colloids; ultrasonic gel (USG; 1%), polystyrenic sulphate (PSS; 0.1%) and polyallylamine (PAA; 3%) and ursodeoxycholic acid (UDCA; 4%). With the polymer sodium alginate (SA; 1.2%) and the copolymer poly L ornithine (PLO; 1%), and test the microcapsule properties as well as cell viability and functionality of the encapsulated ß-cells. This study also aimed to investigate the impact of UDCA on insulin production and the level of pro-inflammatory properties, post microencapsulation. METHOD: The pancreatic ß-cells, NIT-1 were encapsulated with a mixture of SA, PLO, USG, PSS and PAA without UDCA (control) or with UDCA (test). Both formulations and microcapsules were examined for mechanical strength, surface composition and thermal and chemical biocompatibilities. The microencapsulated cells were examined for bioenergetics, and production of inflammatory biomarkers. UDCA distribution within the microcapsules was also examined. RESULTS: Cell viability remained low after the addition of PSS, PAA and USG, while the incorporation of UDCA enhanced cell viability (p &lt; 0.01), cellular bioenergetics and metabolism (p &lt; 0.01), reduced the level of inflammatory biomarkers TNF-a (p &lt; 0.01), IFN-? (p &lt; 0.01) and IL-6 (p &lt; 0.01) and thermal stability was maintained. CONCLUSION: The incorporation of PSS, PAA, USG and UDCA at 0.1:3:1:1 ratio respectively, produced stable and functional microcapsules suggesting potential applications in cell microencapsulation and diabetes treatment

The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study

In recent studies, we designed multi-compartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in an animal model of type 2 diabetes (T2D). Probucol (PB) is a highly lipophilic, antihyperlipidemic drug with potential antidiabetic effects. PB has low bioavailability and high inter-individual variations in absorption, which limits its clinical applications. In a new study, the bile acid, taurocholic acid (TCA), exerted permeation enhancing effects in vivo. Accordingly, this study aimed to design and characterize TCA-based PB microcapsules and examine the effects of TCA on the microcapsules’ morphology, stability, and release profiles. Microcapsules were prepared using the polymer sodium alginate (SA). Two types of microcapsules were produced, one without TCA (PB-SA, control) and one with TCA (PB-TCA-SA, test). Microcapsules were studied in terms of morphology, surface structure and composition, size, drug contents, cross-sectional imaging (using microtomography (Micro-CT) analysis), Zeta potential, thermal and chemical profiles, rheological parameters, swelling, mechanical strength, and release studies at various temperature and pH values. The production yield and the encapsulation efficiency were also studied together with in vitro efficacy testing of cell viability at various glucose concentrations and insulin and TNF-a production using clonal-mouse pancreatic ß-cells. PB-TCA-SA microcapsules showed uniform structure and even distribution of TCA within the microcapsules. Drug contents, Zeta potential, size, rheological parameters, production yield, and the microencapsulation efficiency remained similar after TCA addition. In vitro testing showed PB-TCA-SA microcapsules improved ß-cell survival under hyperglycemic states and reduced the pro-inflammatory cytokine TNF-a while increasing insulin secretions compared with PB-SA microcapsules. PB-TCA-SA microcapsules also showed good stability, better mechanical (p &lt; 0.01) and swelling (p &lt; 0.01) characteristics, and optimized controlled release at pH 7.8 (p &lt; 0.01) compared with control, suggesting desirable targeted release properties and potential applications in the oral delivery of PB in T2D

Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic ß-cell line

CONTEXT: We have shown that the primary bile acid, cholic acid (CA), has anti-diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D). OBJECTIVE: This study aimed to encapsulate CA with PB and examine the formulation and surface characteristics of the microcapsules. We also tested the microcapsules' biological effects on pancreatic ß-cells. METHODS: Using the polymer, sodium alginate (SA), two formulations were prepared: PB-SA (control), and PB-CA-SA (test). Complete characterizations of the morphology, shape, size, chemical, thermal, and rheological properties, swelling and mechanical strength, cross-sectional imaging (Micro CT), stability, Zeta-potential, drug contents, and PB release profile were carried out, at different temperature and pH values. The microcapsules were applied to a NIT-1 cell culture and the supernatant was analyzed for insulin and TNF-a concentrations. RESULTS: CA incorporation optimized the PB microcapsules, which exhibited pseudoplastic-thixotropic rheological characteristics. The size of the microcapsules remained similar after CA addition, and the microcapsules showed even drug distribution and no chemical alterations of the excipients. Micro-CT imaging, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy showed consistent microcapsules with uniform shape and morphology. PB-CA-SA microcapsules enhanced NIT-1 cell viability under hyperglycemic states and resulted in improved insulin release as well as reduced cytokine production at the physiological glucose levels. CONCLUSIONS: The addition of the primary bile acid, CA, improved the physical properties of the microcapsules and enhanced their pharmacological activity in vitro, suggesting potential applications in diabetes treatment

Inflammatory bowel disease: clinical aspects and treatments

Marc Fakhoury,1 Rebecca Negrulj,2 Armin Mooranian,2 Hani Al-Salami2 1Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, Montreal, QC, Canada; 2Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Pharmacy, Curtin University, Perth, WA, Australia Abstract: 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&#39;s own immune system. This inflammatory condition encompasses two major forms, known as Crohn&#39;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. Keywords: inflammatory bowel disease, Crohn&#39;s disease, ulcerative colitis, cytokine

Characterization of a novel bile acid-based delivery platform for microencapsulated pancreatic ß-cells.

Introduction: In a recent study, we confirmed good chemical and physical compatibility of microencapsulated pancreatic β-cells using a novel formulation of low viscosity sodium alginate (LVSA), Poly-L-Ornithine (PLO), and the tertiary bile acid, ursodeoxycholic acid (UDCA). This study aimed to investigate the effect of UDCA on the morphology, swelling, stability, and size of these new microcapsules. It also aimed to evaluate cell viability in the microcapsules following UDCA addition. Materials and methods: Microencapsulation was carried out using a Büchi-based system. Two (LVSA-PLO, control and LVSA-PLO-UDCA, test) pancreatic β-cells microcapsules were prepared at a constant ratio of 10:1:3, respectively. The microcapsules’ morphology, cell viability, swelling characteristics, stability, mechanical strength, Zeta potential, and size analysis were examined. The cell contents in each microcapsule and the microencapsulation efficiency were also examined. Results: The addition of UDCA did not affect the microcapsules’ morphology, stability, size, or the microencapsulation efficiency. However, UDCA enhanced cell viability in the microcapsules 24 h after microencapsulation (p < 0.01), reduced swelling (p < 0.05), reduced Zeta potential (− 73 ± 2 to − 54 ± 2 mV, p < 0.01), and increased mechanical strength of the microcapsules (p < 0.05) at the end of the 24-h experimental period. Discussion and conclusion: UDCA increased β-cell viability in the microcapsules without affecting the microcapsules’ size, morphology, or stability. It also increased the microcapsules’ resistance to swelling and optimized their mechanical strength. Our findings suggest potential benefits of the bile acid UDCA in β-cell microencapsulation

Alginate-combined cholic acid increased insulin secretion of microencapsulated mouse cloned pancreatic ß cells

© 2017 2017 Future Science Ltd. Aim: A semisynthetic primary bile acid (PBA) has exerted hypoglycemic effects in Type 1 diabetic animals, which were hypothesized to be due to its anti-inflammatory and cellular glucose-regulatory effects. Thus, the research purpose aimed to examine antidiabetic effects of a PBA, in terms of cellular inflammation and survival and insulin release, in the context of supporting ß-cell delivery and Type 1 diabetic treatment. Materials & methods: 10 formulations were prepared, five without PBA (control) and five with PBA (test). Formulations were used to microencapsulate pancreatic ß cells and the microcapsules were examined for morphology, cell viability, insulin release and inflammation. Results & conclusion: PBA improved cell viability, insulin release and reduced inflammation in a formulation-dependent manner, which suggests potential use in cell delivery and diabetes treatment

New biotechnological microencapsulating methodology utilizing individualized gradient-screened jet laminar flow techniques for pancreatic ß-cell delivery: bile acids support cell energy-generating mechanisms

In previous studies, we developed a new technique (ionic gelation vibrational jet flow; IGVJF) in order to encapsulate pancreatic β-cells, for insulin in vivo delivery, and diabetes treatment. The fabricated microcapsules showed good morphology but limited cell functions. Thus, this study aimed to optimize the IGVJF technique, by utilizing integrated electrode tension, coupled with high internal vibration, jet-flow polymer stream rate, ionic bath-gelation concentrations, and gelation time stay. The study also utilized double inner/outer nozzle segmented-ingredient flow of microencapsulating dispersion, in order to form β-cell microcapsules. Furthermore, a microcapsule-stabilizing bile acid was added, and microcapsule’s stability and cell functions measured. Buchi-based built-in system utilizing IGVJF technology was screened to produce best microcapsule-containing β-cells with or without a stabilizing-enhancing bile acid. Formed microcapsules were examined, for physical characteristics, and encapsulated cells were examined for survival, insulin release, and inflammatory profiles. Optimized microencapsulating parameters, using IGJVF, were: 1000 V voltage, 2500 Hz frequency, 1 mL/min flow rate, 3% w/v ionic-bath gelation concentration, and 20 min gelation time. Microcapsules showed good morphology and stability, and the encapsulated cells showed good survival, and insulin secretion, which was optimized by the bile acid. Deployed IGVJF-based microencapsulating parameters utilizing stability-enhancing bile acid produced best microcapsules with best pancreatic β-cells functions and survival rate, which, suggests potential application in cell transplantation