title: Novel fibrillar insulin formulations for oral administration: Formulation and in vivo studies in diabetic mice.
abstract: The advantages of oral insulin are well-recognized, yet such formulations are still unavailable. Towards that goal we developed, and evaluated in diabetic ICR mice, two novel insulin microparticles for oral delivery. Although different in structure and shape, both microparticle formulations share: (i) hyaluronan on their surface (ii) fibrillar insulin, loaded at 50-100% efficiency over the insulin range of 1-10mg/ml and (iii) high retention of insulin loads in simulated gastro-intestinal environments. BGL values in diabetic ICR mice were tested over a time span of 8h, following a single oral dose of each formulation, using two protocols: the conventional (12h pre-fasting and 8h fasting); our revised protocol (no pre-fasting, meal at t=4h). In both protocols, initial blood glucose levels (BGL) were 400-600 mg/dL and the novel formulations generated a continuous reduction of BGL. Results in the revised protocol, that mimics human eating habits, were more pronounced, providing stable (over several hours) glucose reductions approaching non-diabetic BGL values. These two fibrillar insulin formulations, and the fibrillar form for therapeutic proteins, merit further studies.
authors.affiliation: Department of Biochemistry, the George W. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Dekel
authors.forename: Y
authors.initials: Y
authors.lastname: Glucksam
authors.forename: R
authors.initials: R
authors.lastname: Margalit
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D004304:Dosage Forms; D004355:Drug Stability; D006820:Hyaluronic Acid / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010316:Particle Size; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D004304:Dosage Forms; D007004:Hypoglycemic Agents; D007328:Insulin; D006820:Hyaluronic Acid