Comparing the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption.

Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 100889084 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-8593 (Electronic) Linking ISSN: 15209156 NLM ISO Abbreviation: Diabetes Technol Ther Subsets: MEDLINE

Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., c1999-

Liposomes* ; Microbubbles*; Hypoglycemic Agents/*pharmacokinetics ; Insulin/*administration & dosage ; Insulin/*pharmacokinetics ; Pharmaceutical Vehicles/*pharmacokinetics ; Respiratory Mucosa/*metabolism; Absorption ; Animals ; Biological Availability ; Biological Transport ; Cell Line ; Cell Survival/drug effects ; Humans ; Hydrogenation ; Hypoglycemia/chemically induced ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/toxicity ; Insufflation ; Insulin/pharmacology ; Insulin/toxicity ; Male ; Particle Size ; Pharmaceutical Vehicles/administration & dosage ; Pharmaceutical Vehicles/chemistry ; Pharmaceutical Vehicles/toxicity ; Phosphatidylcholines/chemistry ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests

Background: The present study investigated the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption.
Methods: Two types of phospholipid-based vesicle-liposomes and microbubbles-were prepared, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity test was used to evaluate their in vitro toxicity in A549 cells. Cellular uptake of insulin combined with liposomes or microbubbles was determined using A549 cells. With intratracheal insufflation of Sprague-Dawley rats, an insulin mixture with liposomes or microbubbles was administered to assess its potential for promoting drug pulmonary absorption.
Results: Both liposomes and microbubbles had a narrow and monodispersed size distribution with average diameter of 3.1 μm and 1.0 μm, respectively. From the MTT cytotoxicity test, a phospholipid-based vesicle concentration of <25% (vol/vol) in the final volume was the safe dosage range that could avoid severe cytotoxic effects. The intracellular uptake amount of insulin in the insulin-microbubble mixture was significantly higher than that in the insulin-liposome mixture. The minimum reductions of the blood glucose concentration produced by insulin-microbubble and insulin-liposome mixtures were 60.8% and 35.0% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.6% and 30.8%, respectively.
Conclusions: Microbubbles have much better efficiency than liposomes in the rate and extent of insulin pulmonary absorption. Microbubbles might be recommended as a potential agent for enhancing protein intrapulmonary absorption.

0 (Hypoglycemic Agents)
0 (Insulin)
0 (Liposomes)
0 (Pharmaceutical Vehicles)
0 (Phosphatidylcholines)

Date Created: 20110423 Date Completed: 20111103 Latest Revision: 20111117

20240104

10.1089/dia.2010.0231

21510752