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

Drug Permeation across the Blood-Brain Barrier: Applications of Nanotechnology

The blood-brain barrier (BBB) is a neurobiological frontier that isolates brain tissues from the blood vascular system. Its main role is to protect the brain and the central nervous system from external fluctuations in hormones, nutrients and drugs, while allowing the passage of water and small lipophilic molecules. Diffusion across the BBB can occur through several biological mechanisms, but the most common one is simple diffusion, which mainly depends on the size, lipid solubility and concentration gradient of the molecule. Because of the highly dense network of capillary endothelium cells found in the BBB, most of the drugs are not able to cross this physiological barrier. Delivering therapeutic agents to the brain is thus a big challenge, which may prevent treatment of important neurological diseases. In order to overcome this difficulty, researchers have used nanotechnology to help the passage of drugs across the BBB. Nanotechnology has significantly contributed to the field of biotechnology by improving the strategies for drug delivery, and by providing novel carriers for safe and effective brain targeting. The aim of this review is to discuss in more details the anatomical structure and the functions of the BBB, as well as its significance in neurological diseases. A closer look will be given at the transport mechanisms across the BBB. This review finally explores the most recent advances in the field of nanotechnology for drug delivery in the brain, and gives meaningful examples of delivery systems developed including the micelles, liposomes, dendrimers, microcapsules and polymeric nanoparticles

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

Influence of the Main Filter on QRS-amplitude and Duration in Human Electrocardiogram.

Accurate measurement of electrocardiograms (ECG) is critical for effective diagnosis of patient’s cardiac functions. Detailed examination of filters’ effects on ECG accuracy, reproducibility and robustness covering a wide range of available commercial products can provide valuable information on the relationship between quality and effectiveness of filters, and assessments of patients’ cardiac functions. In this study, ECG device with 12 leads and built-in filters used for ECG measurements was assessed on human volunteers. Results showed that with respect to measuring QRS wave duration and R-amplitude variation, there was a 4 % inaccuracy when the main filter was ON and OFF, and R-amplitude variation was most pronounced in the V4 lead. Accordingly, variability of R-amplitude and length of QRS wave can be reduced by the use of appropriate lead, and filter activation during the ECG assessment

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

Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat

Major problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are known for their hypoglycemic effect and as promoters of drug penetration across biological membranes. Accordingly, the aim of this study is to investigate whether the bile acid (deoxycholic acid) can change the permeation of gliclazide, through the blood brain barrier of a rat model type-1 diabetes. Twenty-four male Wistar rats were randomly allocated to four groups, of which, two were given alloxan intraperitoneally (100 mg/kg) to induce diabetes. One diabetic group and one healthy group were given a bolus gliclazide intra-arterially (20 mg/kg), while the other two groups apart from gliclazide got deoxycholic acid (4 mg/kg) subcutaneously. Blood samples were collected 30, 60, 150, and 240 seconds after dose, brain tissues were immediately excised and blood glucose and gliclazide concentrations were measured. Penetration of gliclazide in groups without deoxycholic acid pretreatment was increased in diabetic animals compared to healthy animals. Also in both, the healthy and diabetic animals, deoxycholic acid increased the permeation of gliclazide through that in BBB