methylcellulose and Diabetes-Mellitus--Type-2

Exenatide(EXE) is an anti-hyperglycemic agent approved for treating type 2 diabetes by the Food and Drug Administration(FDA). However, twice-daily injection of exenatide is inconvenient for most of the patients.. In this study, biotinylated trimethylated chitosan(Bio-TMC) based nanoparticles were proposed to promote oral absorption of exenatide. Realizing the oral administration of exenatide is very important to alleviate patient suffering and improve patient compliance.

Topics: Animals; Chitosan; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Carriers; Exenatide; Humans; Methylcellulose; Mice; Nanoparticles; Particle Size; Spectroscopy, Fourier Transform Infrared; Tissue Distribution

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~2min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously. The system comprised of chitosan-modified porous silicon (CSUn) nanoparticles, which were coated by an enteric polymer, hydroxypropylmethylcellulose acetate succinate MF, using aerosol flow reactor technology. A non-obese T2DM rat model induced by co-administration of nicotinamide and streptozotocin was used to evaluate the in vivo efficacy of the nanosystem. The oral administration of H-CSUn nanoparticles resulted in 32% reduction in blood glucose levels and ~6.0-fold enhancement in pancreatic insulin content, as compared to the GLP-1+DPP4 inhibitor solution. Overall, these results present a promising system for oral co-delivery of GLP-1 and DPP4 inhibitor that could be further evaluated in a chronic diabetic study.

Topics: Administration, Oral; Animals; Blood Glucose; Chitosan; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucagon-Like Peptide 1; Intestine, Small; Methylcellulose; Nanocomposites; Nanoparticles; Rats, Wistar; Silicon

Diabetes is the fastest growing metabolic disease that fails to utilize glucose properly due to insulin deficiency or insulin resistance. Although several limited studies demonstrated non-invasive means of protein delivery, major hurdles for commercial success such as short half-life, enzymatic degradation and low bioavailability still remain to overcome. Methylcellulose (MC), a hydrophobically-modified cellulose derivative, forms temperature reversible gel in aqueous solution. However, as the gelling temperature of MC is higher than body temperature, it should be lowered to below body temperature for practical clinical application. In order to decrease gelling temperature and increase bio-compatibility and bio-elimination of MC, the molecular weight of MC was decreased using enzymatic degradation method and confirmed by gel permeation chromatography. Bio-elimination of low molecular weight (LMw) MC was confirmed with non-invasive live image and ex vivo experiment. The exenatide and FGF 21 were physically loaded 100% into LMwMC-based thermo-reversible gel and slowly released from gel with no initial bursts. Exenatide-loaded LMwMC gel showed reduction of blood glucose level for a week in type 1 diabetic animal model. FGF 21-loaded LMwMC gel reduced glucose level to normal condition and maintained over 10 days in type 2 diabetic animal model. LMwMC-based thermo-reversible and injectable hydrogel provides a strong potential to be efficient protein drug delivery system for the treatment of type 1 and type 2 diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Exenatide; Fibroblast Growth Factors; Gels; Hypoglycemic Agents; Male; Methylcellulose; Mice; Mice, Inbred BALB C; Molecular Weight; Peptides; Pharmaceutic Aids; Thermodynamics; Tissue Distribution; Venoms

The principle aim of this study was to design a controlled release (CR), bioadhesive formulation of miglitol (in form of pellets) which would regulate the post-prandial glucose levels via reversible inhibition of α-glucosidase enzyme as well as by modulating the glucagon-like peptide-1 (GLP-1) pathway in non-diabetic canines. A multilayered pellet formulation which was both bioadhesive (because of hydroxy propyl methyl cellulose polymer) and CR (because of the ethyl cellulose layer) was formulated. We report a novel finding that the CR formulation of miglitol (S3) induced a 2.2-fold elevation in the C(max) as well as the overall AUC(0-24) of GLP-1 values in comparison to the non-CR (immediate release (IR) formulation). The S3 formulation also resulted in better, steady, and prolonged control of glucose levels over a time period of 7 h in comparison to the IR formulation possibly due to combination of both, prolonged inhibition of the α-glucosidase enzyme and enhanced plasma GLP-1 levels. The S3 formulation was stable with no changes in the dissolution profiles at both of the stability conditions tested, 25°C/60% RH and 40°C/75% RH. Aqueous polymeric coating of the pellets (in contrast to coating using organic solvents) resulted morphologically in a uniform polymeric film and also releases profiles with lower burst effect. Curing played a significant role in determining release profile of the pellets, prepared by aqueous polymeric coating method.

Topics: 1-Deoxynojirimycin; alpha-Glucosidases; Animals; Biological Availability; Blood Glucose; Cellulose; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dogs; Drug Implants; Enteroendocrine Cells; Glucagon-Like Peptide 1; Glycoside Hydrolase Inhibitors; Intestine, Small; Male; Methylcellulose; Polymers; Postprandial Period; Rats; Rats, Sprague-Dawley

Hydroxypropylmethylcellulose (HPMC) is a modified cellulose fiber that creates a viscous solution in the gastrointestinal tract. The present study examined the dose-response characteristics of high-viscosity (HV)-HPMC consumption on postprandial glucose and insulin levels in men and women at increased risk for type 2 diabetes mellitus.. Subjects were a subset of participants in two trials with elevated peak postprandial glucose [>or=7.8 mmol/L (>or=140 mg/dL)] and body mass index (BMI) >or=27 kg/m(2). Subjects (n = 39) consumed breakfast meals containing 75 g of carbohydrate, each of which contained 1, 2, 4, or 8 g of HV-HPMC or a cellulose control in a randomized, double-blind manner. Each subject completed tests with control and two HV-HPMC doses.. Peak glucose concentration was lower than control (all P < 0.01) following 2 g (10%), 4 g (18%), and 8 g (20%) of HV-HPMC. Peak insulin was also reduced (P < 0.01) following 2 g (32%), 4 g (35%), and 8 g (46%) of HV-HPMC doses versus control. Incremental areas for glucose from 0 to 120 min were reduced by 8-40% versus control but only reached significance for the 4-g and 8-g conditions, whereas incremental areas under the insulin curves were reduced by 14-53% (P < 0.01 for 2, 4, and 8 g of HV-HPMC).. Among subjects at risk for type 2 diabetes mellitus, 1.0-8.0 g of HV-HPMC blunted postprandial glucose and insulin responses in a dose-dependent manner. Additional research is warranted to assess whether chronic consumption might retard the development or progression of glucose intolerance.

Topics: Adult; Area Under Curve; Blood Glucose; Body Mass Index; Cholesterol, HDL; Diabetes Mellitus, Type 2; Female; Humans; Hypromellose Derivatives; Male; Methylcellulose; Middle Aged; Risk Factors; Viscosity

The emerging new fixed dose combination of metformin hydrocholride (HCl) as sustained release and glipizide as immediate release were formulated as a bilayer matrix tablet using hydroxy propyl methyl cellulose (HPMC) as the matrix-forming polymer, and the tablets were evaluated via in vitro studies. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. In vitro release studies were carried out at a phosphate buffer of pH 6.8 with 0.75% sodium lauryl sulphate w/v using the apparatus I (basket) as described in the United States Pharmacopeia (2000). The release kinetics of metformin were evaluated using the regression coefficient analysis. There was no significant difference in drug release for different viscosity grade of HPMC with the same concentration. Tablet thus formulated provided sustained release of metformin HCl over a period of 8 hours and glipizide as immediate release.

Topics: Chemistry, Pharmaceutical; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Drug Combinations; Excipients; Glipizide; Hypoglycemic Agents; Hypromellose Derivatives; Metformin; Methylcellulose; Sodium Dodecyl Sulfate; Tablets; Technology, Pharmaceutical; Viscosity

Topics: Contact Lenses; Corneal Diseases; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Epithelium, Corneal; Humans; Hyaluronic Acid; Laser Coagulation; Methylcellulose

Topics: Amnion; Contact Lenses; Corneal Diseases; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Epithelium, Corneal; Humans; Hyaluronic Acid; Laser Coagulation; Methylcellulose

To describe the effect of coupling solutions used during laser photocoagulation on the ocular surface of patients with noninsulin-dependent diabetes mellitus (NIDDM).. A prospective case-controlled study.. Ninety-two eyes of 46 NIDDM patients with clinically significant macular edema, poor metabolic control of diabetes, and peripheral neuropathy and 100 eyes of 50 normal control subjects were studied. The patients' eyes were assigned to argon green focal/grid laser photocoagulation using an applanation contact lens and one of the coupling fluids; 2% methocel, Thilo-Tears Gel, 1.4% sodium hyaluronate, or 0.9% simple saline. The control subjects received time-matched three-mirror contact lens fundus examinations. All subjects underwent corneal sensitivity measurements, Schirmer test, tear film breakup time, and corneal fluorescein staining before as well as 3 and 8 days after the laser procedures and contact lens examinations. Patients with corneal problems persisting after 8 days were followed longer.. Diabetic eyes assigned to 2% methocel and 1.4% sodium hyaluronate had significantly lower mean corneal sensitivities and break-up time values as well as significantly higher mean fluorescein staining scores at all examination points after laser photocoagulation. All diabetic eyes with aqueous deficiency assigned to 2% methocel and 1.4% sodium hyaluronate developed delayed corneal epithelial healing.. The use of viscous coupling solutions during applanation contact lens-aided laser procedures may be detrimental for the corneal epithelium in poorly controlled NIDDM patients with peripheral neuropathy and coexisting aqueous deficiency.

Topics: Adult; Aged; Case-Control Studies; Contact Lenses; Corneal Diseases; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Epithelium, Corneal; Female; Fluorescein; Fluorophotometry; Humans; Hyaluronic Acid; Laser Coagulation; Macular Edema; Male; Methylcellulose; Middle Aged; Ophthalmic Solutions; Prospective Studies; Tears; Wound Healing