Journal
DIABETES TECHNOLOGY & THERAPEUTICS
Volume 13, Issue 10, Pages 1013-1021Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/dia.2011.0113
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Funding
- National Natural Science Funds [81071164, 81071277]
- Natural Science Foundation of Zhejiang Province [Y2110587, Y2080915]
- Natural Science Foundation of Beijing [7112100]
- Wenzhou Bureau of Science and Technology [H20100017, S20100049]
- Zhejiang Province Health Department [2009QN022, 2010ZQ007, 2011ZDA017]
- Zhejiang Province Education Department [Y201016664]
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Background: Gas-filled phospholipid-based ultrasonic microbubbles (PUMs) are widely used in diagnostic imaging. The micro-or nanoparticle size and the physiochemical nature of shell provide the potential for a new way to improve pulmonary absorption for peptides and proteins. Methods: Male Sprague-Dawley rats were fasted for 12 h. Then insulin solution and insulin-PUM mixture solution were administered by intratracheal instillation. The hypoglycemic effect was observed to evaluate insulin absorption after lung administration. Fluorescein isothiocyanate-dextran (molecular mass, 4 kDa) was used as the index of evaluating drug alveolar deposition and absorption by visualization techniques. Results: Administration of insulin solution containing PUMs significantly reduced the blood glucose levels of Sprague-Dawley rats, compared with administration of insulin-only solution. The minimum reductions of the blood glucose concentration produced by insulin solution containing PUMs and by an insulin-only solution reached 60.81% and 34.60% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.58% and 29.09%, respectively. Histopathological study of the lung showed no changes in the morphology of the pulmonary alveoli after administration to these drugs. Only a slight inflammatory cell infiltration in the alveoli could be found in some rats. Conclusion: These results suggested that PUMs might be used as an effective way to improve pulmonary absorption for peptides and proteins.
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