Novel mucosal insulin delivery systems based on fusogenic liposomes.
OBJECTIVE
Fusogenic liposomes (FLs) are unique delivery vehicles capable of introducing their contents directly into the cytoplasm with the aid of envelope glycoproteins of Sendai virus (SeV). The objective of this study was to evaluate the potential of FL to improve the mucosal absorption of insulin from rat intestinal membranes.


METHODS
The FLs containing insulin were prepared by fusing insulin-loaded liposomes with inactivated SeV particles and were administered directly into the ileal, the colonic, and the rectal loops (10 IU/kg).


RESULTS
The FL successfully enhanced the insulin absorption and induced a significant hypoglycemic effect following the colonic and the rectal administration without detectable mucosal damage. This enhancing effect of insulin absorption was further improved by increasing the amount of insulin loaded in the FL and by coencapsulating insulin-degrading enzyme inhibitor. In contrast, the insulin absorption was not increased by the ileal administration of FL because the mucous/glycocalyx layers overlaid on the ileal epithelium impede the fusion of FL to the intestinal mucosa.


CONCLUSIONS
Our results indicated that FL is a useful carrier for improving the absorption of poorly absorbable drugs, such as insulin, via the intestinal tract.
Goto
Takahiro
T
Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
Morishita
Mariko
M
Nishimura
Ken
K
Nakanishi
Mahito
M
Kato
Atsushi
A
Ehara
Jumpei
J
Takayama
Kozo
K
D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007339:Insulysin / Q000037:antagonists & inhibitors; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008081:Liposomes; D008297:Male; D008566:Membranes / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D029082:Sendai virus / Q000235:genetics
D004337:Drug Carriers; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes; D007770:L-Lactate Dehydrogenase; D007339:Insulysin