Glucose-sensing pulmonary delivery of human insulin to the systemic circulation of rats.
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.
Karathanasis
Efstathios
E
Chemical Engineering Department, University of Houston, Houston, TX, USA.
Bhavane
Rohan
R
Annapragada
Ananth V
AV
D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D002214:Capsules; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000336:Aerosols; D002214:Capsules; D004337:Drug Carriers; D007328:Insulin; D008081:Liposomes; D005947:Glucose