Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs

Hyaluronic acid (HA) and recombinant human insulin were co-spray dried to form a dry powder suitable for inhalation (Mass Median Aerodynamic Diameter, MMAD=1 to 4 μm). Insulin systemic levels and corresponding glucose levels were monitored following administration of the microparticles to the lungs...

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Bibliographic Details
Published in:Journal of controlled release 2003-09, Vol.91 (3), p.385-394
Main Authors: Surendrakumar, K., Martyn, G.P., Hodgers, E.C.M., Jansen, M., Blair, J.A.
Format: Article
Language:English
Subjects:
Administration, Inhalation
Animals
Biological and medical sciences
Chemistry, Pharmaceutical
Delayed-Action Preparations - administration & dosage
Delayed-Action Preparations - pharmacokinetics
Dogs
Drug Delivery Systems - methods
General pharmacology
Hormones. Endocrine system
Humans
Hyaluronic Acid - administration & dosage
Hyaluronic Acid - pharmacokinetics
hydroxypropyl cellulose
Insulin
Insulin - administration & dosage
Insulin - pharmacokinetics
Lung - drug effects
Lung - physiology
Male
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacokinetics
Pharmacology. Drug treatments
Powders
Pulmonary delivery
sodium hyaluronate
Sodium hyaluronate/hyaluronic acid
Sustained release
zinc
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Summary:Hyaluronic acid (HA) and recombinant human insulin were co-spray dried to form a dry powder suitable for inhalation (Mass Median Aerodynamic Diameter, MMAD=1 to 4 μm). Insulin systemic levels and corresponding glucose levels were monitored following administration of the microparticles to the lungs of male Beagle dogs. Release kinetics were modified by addition of excess zinc ions (Zn 2+) or hydroxypropyl cellulose (HPC). HA formulations containing insulin (10%w/w) were found to extend the mean residence time (MRT) and terminal half-life ( t 1 2 ) when compared to spray dried pure insulin. Addition of Zn 2+ also improved MRT (>9 fold), AUC/dose (2.5 fold) and T max (by a factor of 3) when compared to spray dried pure insulin. Addition of HPC improved MRT (>7 fold), AUC/dose (5 fold) and T max (by a factor of 3) when compared to spray dried pure insulin. Our results demonstrate the potential of HA-based dry powder drug delivery systems in the pulmonary controlled release of insulin.
ISSN:0168-3659
1873-4995
DOI:10.1016/S0168-3659(03)00263-3