title: Development and evaluation of in situ gel-forming system for sustained delivery of insulin.
abstract: Phase-sensitive in situ gel-forming controlled release formulations of insulin were prepared using poly(lactide-co-glycolide) and a solvent system consisting of various proportions of benzyl benzoate and benzyl alcohol. The in vitro release samples of formulations were assayed for insulin content by enzyme linked immunosorbent assay. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and circular dichroism spectroscopy studies of released insulin confirmed its conformational stability. The stability of insulin in the formulation was assessed using Fourier transform infrared spectroscopy. Rheological properties of the formulations, assessed under isothermal conditions, showed dilatant behavior of all the formulations. In vivo studies were carried out on the optimized formulations vis-à-vis pure insulin in mice and blood glucose levels were monitored for 15 days. Mean percentage reduction in blood glucose levels was calculated in all the animals and the results analyzed using ANOVA. The studies construed better pharmacodynamic response for the two optimized formulations in controlling the blood glucose levels vis-à-vis routine once-a-day administration of insulin. The subcutaneous tissues, further subjected to scanning electron microscopy studies and histopathological examinations, ascertained the biocompatibility of the formulation.
authors.affiliation: University Institute of Pharmaceutical Sciences (UGC Centre of Advanced Studies), Panjab University, Chandigarh, India. sanjudhawan@rediffmail.com
authors.forename: Sanju
authors.initials: S
authors.lastname: Dhawan
authors.forename: Rishi
authors.initials: R
authors.lastname: Kapil
authors.forename: Deepak N
authors.initials: DN
authors.lastname: Kapoor
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects*; D002942:Circular Dichroism; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004591:Electrophoresis, Polyacrylamide Gel; D005782:Gels / Q000737:chemistry / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D011098:Polyglactin 910 / Q000737:chemistry* / Q000378:metabolism; D012212:Rheology; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001672:Biocompatible Materials; D001786:Blood Glucose; D003692:Delayed-Action Preparations; D005782:Gels; D007004:Hypoglycemic Agents; D007328:Insulin; D012997:Solvents; D011098:Polyglactin 910