1. Chitosan-graft-PAMAM–alginate core–shell nanoparticles: a safe and promising oral insulin carrier in an animal model
P. Mukhopadhyay, P. P. Kundu*. RSC Adv.,2015, 5, 93995–94007
Alginate (ALG) is another water soluble, pH sensitive natural polysaccharide, containing varying amounts of 1,4-linked β-D-mannuronic acid (M) and a-L-guluronic acid (G) residues, and is usually extracted from brown seaweed. It has also gained much attention in oral insulin delivery due to its shrinkage at lower pH, enabling complete retention of encapsulated insulin during the passage through the GI tract, hence providing protection against enzymatic deactivation. Biodegradability, biocompatibility, low toxicity, low immunogenicity and good Mucoadhesion facilitate its wide application in oral drug delivery research. Nanoparticles can easily be formulated using ALG either by physical or chemical crosslinking for the sustained drug release studies. Physical crosslinking is usually preferred over chemical crosslinking26 to avoid toxicity issues. Calcium, a divalent cation is reported to crosslink alginate and also maintains the biological eﬃcacy of insulin.
2. Adsorption of human insulin on single-crystal gold surfaces investigated by in situ scanning tunnelling microscopy and electrochemistry
Anna C. Welinder, Jingdong Zhang, Dorte B. Steensgaardb, Jens Ulstrup*. Phys.Chem.Chem.Phys., 2010, 12, 9999–10011
Insulin is one of the most important hormones in the regulation of cellular uptake of glucose followed by conversion of glucose to glycogen in the liver. The active form is the insulin monomer, a small protein (MW 5800 amu) holding 51 amino acids in two strands, the A- and the B-strand, and folded into a globular tertiary structure assisted by altogether three disulﬁde groups. The venue for insulin biosynthesis is the pancreatic β-cells. Stimulated by glucose uptake, insulin is released to the blood as the physiologically active monomeric form, Inadequate insulin production or cellular resistance to insulin (i.e. various forms of diabetes) leads to shortage of glucose supply to the cells, ultimately with a whole range of recognized complications. Dimer insulin, Fig. 1 is formed by hydrophobic monomer/monomer interactions typically at concentrations above 1 ng mL-1. Due to this self-association of zinc free insulin, both monomeric and dimeric forms are the species that prevail under the conditions used in the present work.
3. Probing adsorption and aggregation of insulin at a poly(acrylic acid) brush
Florian Evers, Christian Reichhart, Roland Steitz, Metin Tolana, Claus Czeslik*. Phys.Chem.Chem.Phys., 2010, 12, 4375–4382
In a series of studies, distinct aggregation pathways of insulin have been described which result in diﬀerent amyloid ﬁbril morphologies. Generally, by lowering the pH value, insulin hexamers are broken up into dimers and monomers. Raising the temperature leads to a destabilization of the native conformation of insulin molecules, which favours the formation of amyloid structures rich inβ-sheet content. Furthermore, adding salt to an insulin solution shields the electrostatic repulsion of the positively charged insulin molecules at low pH values, thereby facilitating their aggregation.