Glargine and degludec: Solution behaviour of higher dose synthetic insulins.

Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers ("multi-hexamerisation"). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24-40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes.

The Effectiveness of Lifestyle Adaptation for the Prevention of Prediabetes in Adults: A Systematic Review.

Diabetes prevalence is increasing exceptionally worldwide and with this come associated healthcare costs. The primary outcome of this systematic review was to assess glycaemic control and incidence of Type 2 diabetes mellitus (T2DM) diagnosis after exercise and dietary intervention (measured with any validated scale). The secondary outcome assessed body mass index change, weight change, and physical exercise capacity after diet and exercise intervention (measured with any validated scale). 1,780 studies were identified from searching electronic databases. Relevant studies went through a selection process. The inclusion criteria for all studies were people with prediabetes diagnosed by either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). Lifestyle adaptation reduced the incidence of diabetes development more than standard treatment. Furthermore, better glycaemic control, improved physical exercise capacity, and increased weight reduction were observed with lifestyle intervention over standard treatment. Finally, improvements over the long term deteriorated, highlighting problems with long-term adherence to lifestyle changes. Overall, cumulative incidence of diabetes is drastically reduced in the intervention groups compared to control groups (standard care). Furthermore, glycaemic control was improved in the short term, with many participants reverting to normoglycaemia.

Molecular weight distribution analysis by ultracentrifugation: adaptation of a new approach for mucins.

Mucins are the key macromolecular component of mucus, nature's natural lubricant, and one of the most important physical properties is their molecular weight distribution. A new approach for polydisperse polymers was recently published based on sedimentation velocity in the analytical ultracentrifuge and converts a distribution of sedimentation coefficient g(s) vs. s plot into a distribution of molecular weight utilising the power-law or scaling relationship between the sedimentation coefficient and molecular weight, s=κsMw(b) where s is the sedimentation coefficient, Mw is the weight average molecular weight and κs and b are characteristic coefficients related to conformation. We investigate the possibility of using a large database of previously published values of s an M to define κs and b for both aqueous solution and aqueous solution supplemented by 6M guanidine hydrochloride (a solvent which helps to minimise sample degradation). These values are then applied to a study of the molecular weight distributions of preparations of human gastric mucin in the different solvents and at different stages of purification.

Polysaccharide drug delivery systems based on pectin and chitosan.

Chitosans and pectins are natural polysaccharides which show great potential in drug delivery systems. Chitosans are a family of strongly polycationic derivatives of poly-N-acetyl-D-glucosamine. This positive charge is very important in chitosan drug delivery systems as it plays a very important role in mucoadhesion (adhesion to the mucosal surface). Other chitosan based drug delivery systems involve complexation with ligands to form chitosan nanoparticles with can be used to encapsulate active compounds. Pectins are made of several structural elements the most important of which are the homogalacturonan (HG) and type I rhamnogalacturonan (RG-I) regions often described in simplified terms as the "smooth" and "hairy" regions respectively. Pectin HG regions consist of poly-glacturonic acid residues which can be partially methyl esterified. Pectins with a degree of methyl esterification (DM) > 50% are known as high methoxyl (HM) pectins and consequently low methoxyl (LM) pectins have a DM less than 50%. Low methoxyl pectins are of particular interest in drug delivery as they can form gels with calcium ion (Ca2+) which has potential applications especially in nasal formulations. In this chapter we will discuss the physicochemical properties of both chitosans and pectins and how these translate to current and potential drug delivery systems.