Lipid emulsions as vehicles for enhanced nasal delivery of insulin.
The objective of this work is to explore lipid emulsion based formulations of insulin as an enhancer of nasal absorption. Insulin was incorporated into the aqueous phases of water-in-oil (w/o) and oil-in-water (o/w) emulsions. The formulations were perfused through the nasal cavity of rats in situ. Enhancement of insulin absorption was observed when insulin was incorporated into the continuous aqueous phase of an o/w emulsion. The presence of a small fraction of oil droplets along with insulin in the aqueous phase appeared to favor insulin absorption. When the oil phase constitutes the external phase, as in w/o emulsion, no insulin absorption was noted. Inhibition of insulin absorption might arise from a rate limiting barrier effect of the membrane completely covered by a stagnant oil layer. The in situ model was validated by in vivo experiments, which also revealed an increase in insulin absorption with o/w emulsions. However at lower insulin doses there was no statistically significant enhancing effect. In situ perfusion experiments across rat nasal pathway appear to be an appropriate model to study the enhancement effect of nasal formulations.
Mitra
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Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5100 Rockhill Road, Kansas City, MO 64110-2499, USA.
Pezron
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Mitra
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D000281:Administration, Intranasal; D000818:Animals; D016503:Drug Delivery Systems; D004655:Emulsions; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D009296:Nasal Cavity / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013024:Soybean Oil / Q000008:administration & dosage / Q000493:pharmacokinetics
D004655:Emulsions; D007004:Hypoglycemic Agents; D007328:Insulin; D013024:Soybean Oil