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Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats

Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats

Hamishehkar, Hamed, Emami, Jaber, Najafabadi, Abdolhossien Rouholamini, Gilani, Kambiz, Minaiyan, Mohsen, Hassanzadeh, Kambiz, Mahdavi, Hamid, Koohsoltani, Maryam and Nokhodchi, Ali (2010) Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats. Biopharmaceutics and Drug Disposition, 31 (2-3). pp. 189-201. ISSN 0142-2782 (doi:10.1002/bdd.702)

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Abstract

The pulmonary route is an alternative route of administration for the systemic delivery of peptide and proteins with short-half lives. A long-acting formulation of insulin was prepared by encapsulation of protein into respirable, biodegradable microcapsules prepared by an oil in oil emulsification/solvent evaporation method. Insulin-loaded PLGA microcapsules prepared as a dry powder inhaler formulation were administered via the pulmonary route to diabetic rats and serum insulin and glucose concentrations were monitored. Control treatments consisted of respirable spray-dried insulin (RSDI) powder administered by intratracheal insufflation, insulin-loaded PLGA microcapsules and NPH (long-acting) insulin administered by subcutaneous (SC) administration. Pharmacokinetic analysis demonstrated that insulin administered in PLGA microcapsules illustrated a sustained release profile which resulted in a longer mean residence time, 4 and 5 fold longer than those after pulmonary administration of RSDI and SC injection of NPH insulin, respectively. Accordingly, the hypoglycemic profile followed a stable and sustained pattern which remained constant between 10 and 48 h. Results of the in vitro experiments were in good agreement with those of in vivo studies. Bronchoalveolar lavage fluid analysis indicated that microcapsules administration did not increase the activities of lactate dehydrogenase and total protein. However, histological examination of the lung tissue indicated a minor but detectable effect on the normal physiology of the rat lung. These findings suggest that the encapsulation of peptides and proteins into PLGA microcapsules technique could be a promising controlled delivery system for pulmonary administration

Item Type: Article
Uncontrolled Keywords: insulin, PLGA, controlled release, pulmonary delivery, dry powder inhalation
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Pre-2014 Departments: School of Science
School of Science > Department of Medway Sciences
Related URLs:
Last Modified: 14 Oct 2016 09:09
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/3520

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