An In Vivo Experiment to Improve Pulmonary Absorption of Insulin Using Microbubbles

作者:Zhao Ying Zheng; Xu Yan Yan; Li Xing; Lu Cui Tao*; Zhang Lu; Dai Dan Dan; Sun Chang Zheng; Lv Hai Feng; Li Xiao Kun; Yang Wei
来源:Diabetes Technology & Therapeutics, 2011, 13(10): 1013-1021.
DOI:10.1089/dia.2011.0113

摘要

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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