Enhanced absorption of insulin and (Asu(1,7))eel-calcitonin using novel azopolymer-coated pellets for colon-specific drug delivery.
The objective of this study was to estimate colon-specific delivery of insulin and (Asu(1,7))eel-calcitonin using novel azopolymer-coated pellets. In vitro drug-release experiments from the azopolymer-coated pellets containing fluorescein isothiocyanate dextran (MW 4400; FD-4) were carried out by the Japanese Pharmacopoeia (J.P.) XIII rotating basket method with some slight modifications. Little release of FD-4 from the pellets was observed in phosphate buffered saline. However, the release of FD-4 was markedly increased in the presence of rat cecal contents. The intestinal absorption of insulin and (Asu(1,7))eel-calcitonin after oral administration of the azopolymer-coated pellets containing these peptides with camostat mesilate was evaluated by measuring the hypoglycemic and hypocalcemic effects, respectively. A slight decrease in plasma glucose levels was observed following the oral administration of these pellets containing 12.5 IU of insulin compared with the same dose of insulin solution. Camostat mesilate, a protease inhibitor that is incorporated with insulin in these pellets, further decreased the plasma glucose levels in a dose-dependent manner. Similar results were also obtained with the oral administration of pellets containing (Asu(1,7))eel-calcitonin. These findings suggest that azopolymer-coated pellets may be useful carriers for the colon-specific delivery of peptides including insulin and (Asu(1,7))eel-calcitonin.
Tozaki
H
H
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Nishioka
J
J
Komoike
J
J
Okada
N
N
Fujita
T
T
Muranishi
S
S
Kim
S I
SI
Terashima
H
H
Yamamoto
A
A
D000284:Administration, Oral; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005772:Gastrointestinal Transit / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; D002116:Calcitonin