Glucose-sensing pulmonary delivery of human insulin to the systemic circulation of rats

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Authors: Efstathios Karathanasis, Rohan Bhavane, Ananth V Annapragada

Published Date October 2007 Volume 2007:2(3) Pages 501 - 513

DOI: http://dx.doi.org/10.2147/IJN.S

Efstathios Karathanasis¹, Rohan Bhavane², Ananth V Annapragada²

¹Chemical Engineering Department, University of Houston, Houston, TX, USA; ²School of Health Informatics, University of Texas Health Science Center, Houston, TX, USA

Abstract: In an attempt to achieve post-inhalation self-regulated insulin release, we constructed a microparticle agglomerate of nano-sized liposomal particles, with the agglomeration facilitated by cross-linkages capable of cleavage by glucose. The particles exhibited a small aerodynamic diameter within the human respirable range, but a large geometric diameter that prevents macrophage uptake and clearance. Upon intratracheal instillation of the “glucose-sensitive” microparticle into the lungs of rats, hyperglycemic events triggered an acceleration of the release of insulin achieving normoglycemia shortly after “sensing” the elevated systemic glucose. This work is a demonstration of an inhalable particle with long residence times in the lungs capable of modulating insulin release based on systemic glucose levels.

Keywords: self-regulated release, inhaled insulin, agglomerated vesicle technology, liposomes, glucose sensitive particle