Triggered release of inhaled insulin from the agglomerated vesicles: pharmacodynamic studies in rats.
An aerosol insulin carrier based on the agglomerated vesicle technology that the authors have previously advanced [E. Karathanasis et al. J. Control. Release 103 (2005) 159-175] was evaluated in vivo. The carrier consisted of insulin-loaded liposomes cross-linked via chemical bridges cleavable by cysteine. It was speculated that the cleavage of the cross links released internal surface area and possibly resulted in the disruption of the liposomal walls. The result was a rapid release of encapsulated insulin upon contact of the insulin carrier with cysteine. The particles exhibited a small aerodynamic diameter within the respirable range suggesting deposition into the deep lung of humans along with a large geometrical diameter, consistent with long residence time. Indeed the endotracheal instillation of the particles into hyperglycemic rats decreased the glucose levels rapidly while delivery of cysteine triggered a further drop of glucose implying acceleration of insulin release from the carrier. Euglycemic clamp studies verified the accelerated insulin release upon application of cysteine.
Karathanasis
Efstathios
E
Department of Chemical Engineering, University of Houston, Houston, Texas, USA.
Bhavane
Rohan
R
Annapragada
Ananth V
AV
D000280:Administration, Inhalation; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007328:Insulin; D008081:Liposomes