Synthetic long-chain alkyl maltosides and alkyl sucrose esters as enhancers of nasal insulin absorption.
A series of new glycosides with extended alkyl side-chains (C(13-16)) linked to maltose or sucrose were synthesized and tested for their efficacy in enhancing nasal insulin absorption in anesthetized rats. The new reagents were compared to previously tested alkylglycosides with shorter alkyl side chains (C(8-12)). Dose-response studies revealed that within the family of alkylmaltoside derivatives, (C(8-16)), maximal increases in insulin absorption took place when tetradecylmaltoside (C(14)) was added to the formulation. Pentadecylmaltoside (C(15)) and hexadecylmaltoside (C(16)) were less potent at increasing insulin absorption, although both reagents achieved maximal effects when used at higher concentrations. Within the family of alkanoylsucrose derivatives, tridecanoylsucrose (C(13)) and tetradecanoylsucrose (C(14)) were most potent at increasing insulin absorption. Cross-comparisons between alkylmaltoses and alkanoylsucroses showed that the alkyl chain length had a greater impact than the glycoside moiety in determining the potency of a potential insulin-absorption enhancing agent. When tetradecylmaltoside was applied to the nasal mucosa 15 min before insulin was applied, the enhanced insulin absorption was still observed.
Department of Pharmacology and Toxicology, School of Medicine, University of Alabama at Birmingham, 35294-0019, USA. dpillion@uab.edu
Dennis J
DJ
Pillion
Fakhrul
F
Ahsan
John J
JJ
Arnold
Balu M
BM
Balusubramanian
Olga
O
Piraner
Elias
E
Meezan
D000042:Absorption / Q000187:drug effects; D000281:Administration, Intranasal; D000818:Animals; D004952:Esters / Q000737:chemistry; D007328:Insulin / Q000493:pharmacokinetics*; D008297:Male; D008320:Maltose / Q000737:chemistry; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000737:chemistry
D004952:Esters; D007328:Insulin; D013395:Sucrose; D008320:Maltose