Nasal insulin delivery remains a possible alternative for patients with diabetes mellitus in attempting to control blood glucose levels. Nasal insulin administration requires the addition of a surfactant agent to improve systemic absorption of insulin, but this requirement has led to difficulty in identifying safe, effective surfactant agents that could be included in a nasal formulation. Pilot studies by the investigators have shown that some alkylglycosides were effective in promoting insulin absorption following nasal delivery. Alkylglycosides with longer alkyl side chains (i.e. 12-14 carbons in length) were the most effective in enhancing insulin absorption, whereas alkylglycosides with shorter side chains (i.e. 6- 8 carbons in length) were ineffective. In Phase I of this investigation, alkylglycosides with side chains containing 14- 16 carbons were synthesized and their efficacy in enhancing nasal insulin delivery was determined. Tetradecylmaltoside, an alkylglycoside with a 14 carbon side chain, was the most effective reagent at increasing nasal insulin delivery. Independently, this reagent caused little nasal toxicity when applied to rats once a day for 15 days. The extent of the nasal toxicity was dependent on the tetradecylmaltoside concentration used. Phase II studies are intended to; l) assess the stability of nasal insulin formulations containing tetradecylmaltoside; 2) compare the efficacy of nosedrops containing insulin and tetradecylmaltoside verses nasal mist or aerosol of the same formulation in primarily rats (but also rabbits and monkeys too); 3) compare the onset and duration of action of nasal insulin delivery when rapid-acting insulin or intermediate-acting insulin are substituted for regular insulin. (Preliminary data in Appendix l indicates that monomeric LysPro-insulin, regular or NPH-insulin with 0.125% dodecylmaltoside were as efficiently absorbed as each other, giving similar pharmacokinetic/pharmakodynamic profiles); 4) determine the formulation to bring to clinical trials.

Proposed Commercial Applications

NOT AVAILABLE

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
5R42ES008933-03
Application #
6178657
Study Section
Special Emphasis Panel (ZRG2-REN (01))
Program Officer
Heindel, Jerrold
Project Start
1996-09-30
Project End
2002-05-31
Budget Start
2000-09-30
Budget End
2002-05-31
Support Year
3
Fiscal Year
2000
Total Cost
$206,051
Indirect Cost
Name
Cytrx Corporation
Department
Type
DUNS #
825313591
City
San Diego
State
CA
Country
United States
Zip Code
92109