Enhanced rectal absorption of insulin-loaded Pluronic F-127 gels containing unsaturated fatty acids.
The objective of this study was to prepare and to evaluate Pluronic F-127 (PF127) gel containing unsaturated fatty acids such as oleic acid (18:1), eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) as a potential formulation for rectal delivery of insulin. The hypoglycemic effect of insulin was examined following rectal administration of the various formulations in normal rats. Rectal insulin absorption was markedly enhanced, and marked hypoglycemia was induced by all PF127 gels (insulin dose, 5 U/kg) containing different unsaturated fatty acids. PF127 gels containing unsaturated fatty acids presented low tmax mean values indicating that the absorption of insulin occurred very rapidly in the rectum. The relative hypoglycemic efficacy of PF127 gel formulations containing fatty acids such as oleic acid, eicosapentaenoic (EPA) and docosahexaenoic (DHA) were 28.4+/-8.1, 26.8+/-14.3 and 23.1+/-5.7%, respectively. The finding demonstrated that 20% PF127 gels containing unsaturated fatty acids are potential formulations for rectal delivery of insulin.
Barichello
J M
JM
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hoshi University, Ebara-2-4-41, Shinagawa-Ku, Tokyo 142-8501, Japan.
Morishita
M
M
Takayama
K
K
Chiba
Y
Y
Tokiwa
S
S
Nagai
T
T
D000285:Administration, Rectal; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004281:Docosahexaenoic Acids / Q000737:chemistry; D015118:Eicosapentaenoic Acid / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D005782:Gels; D007003:Hypoglycemia / Q000139:chemically induced; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D019301:Oleic Acid / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D005231:Fatty Acids, Unsaturated; D005782:Gels; D007328:Insulin; D020442:Poloxamer; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D015118:Eicosapentaenoic Acid