title: Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.
abstract: An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules.
authors.affiliation: BioSante Pharmaceuticals Inc, 4600 Highlands Parkway, Suites A&B, Smyrna, GA 30082, USA. tmorcol@biosantepharma.com
authors.forename: T
authors.initials: T
authors.lastname: Morçöl
authors.forename: P
authors.initials: P
authors.lastname: Nagappan
authors.forename: L
authors.initials: L
authors.lastname: Nerenbaum
authors.forename: A
authors.initials: A
authors.lastname: Mitchell
authors.forename: S J D
authors.initials: SJ
authors.lastname: Bell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002130:Calcium Phosphates / Q000008:administration & dosage* / Q000737:chemistry; D002364:Caseins / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D002417:Cattle; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D051379:Mice; D016688:Mice, Inbred NOD; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D002130:Calcium Phosphates; D002364:Caseins; D004337:Drug Carriers; D007328:Insulin; C039441:insulin, polyethylene glycol(B1)-; D011092:Polyethylene Glycols; C020243:calcium phosphate