Enhanced pulmonary delivery of insulin by lung lavage fluid and phospholipids.
Pulmonary delivery appears to be the most promising non-parenteral route of insulin administration. In this work, we investigated the enhancement of insulin absorption in the presence of phospholipids and lung lavage fluid in vivo and in vitro. In-vitro experiments of insulin uptake by type II cells showed a significantly enhanced absorption in presence of lavage fluid, compared to various buffer preparations. The same trend was obtained with in-vivo studies of tracheal instillation of insulin. The incorporation of phospholipids as absorption enhancers in 1,2-dipalmitoyl phosphatidylcholine (DPPC) dispersion was compared to blank liposomes. A significantly higher blood glucose decrease was observed with a DPPC-insulin physical mixture compared to liposome, suggesting a possible effect of the phospholipid chain physical state on the insulin in-vivo absorption.
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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.
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D015060:1,2-Dipalmitoylphosphatidylcholine / Q000493:pharmacokinetics*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine