Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes.
OBJECTIVE
The mucoadhesiveness of polymer-coated liposomes was evaluated to develop a novel drug carrier system for oral administration of poorly absorbed drugs such as peptide drugs.


METHODS
Multilamellar liposomes consisting of dipalmitoylphosphati-dylcholine (DPPC)and dicetyl phosphate (DCP) (DPPC: DCP = 8:2 in molar ratio) were coated with chitosan (CS), polyvinyl alcohol having a long alkyl chain (PVA-R) and poly (acrylic acid) bearing a cholesteryl group. The adhesiveness of the resultant polymer-coated liposomes to the rat intestine was measured in vitro by a particle counting method with a Coulter counter. The CS-coated liposomes containing insulin were administered to normal rats and the blood glucose level was monitored.


RESULTS
The existence of polymer layers on the surface of liposomes was confirmed by measuring the zeta potential of liposomes. The CS-coated liposomes showed the highest mucoadhesiveness and the degree of adhesion was dependent on the amount of CS on the surface of the liposomes. The blood glucose level of rats was found to be significantly decreased after administration of the CS-coated liposomes containing insulin. The lowered glucose level was maintained for more than 12h after administration of the liposomal insulin, which suggested mucoadhesion of the CS-coated liposomes in the intestinal tract of the rats.
Takeuchi
H
H
Gifu Pharmaceutical University, Japan.
Yamamoto
H
H
Niwa
T
T
Hino
T
T
Kawashima
Y
Y
D015060:1,2-Dipalmitoylphosphatidylcholine; D000268:Adhesiveness; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002686:Chitin / Q000031:analogs & derivatives; D048271:Chitosan; D004337:Drug Carriers; D005079:Excipients; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008081:Liposomes; D008297:Male; D010755:Organophosphates; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D004337:Drug Carriers; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes; D010755:Organophosphates; D002686:Chitin; D015060:1,2-Dipalmitoylphosphatidylcholine; C002290:dicetylphosphate; D048271:Chitosan