Safety and efficacy of inhaled insulin formulated with alkylglycosides
| dc.contributor.committeeChair | Ahsan, Fakhrul | |
| dc.contributor.committeeMember | Allen, David D. | |
| dc.contributor.committeeMember | Klein, Jochen | |
| dc.contributor.committeeMember | Mehvar, Reza | |
| dc.contributor.committeeMember | Youan, Bi-Botti Celestin | |
| dc.creator | Hussain, Alamdar | |
| dc.date.accessioned | 2016-11-14T23:13:09Z | |
| dc.date.available | 2012-06-01T15:44:19Z | |
| dc.date.available | 2016-11-14T23:13:09Z | |
| dc.date.issued | 2005-12 | |
| dc.degree.department | Pharmaceutical Sciences | |
| dc.description.abstract | The pulmonary route has shown a tremendous promise for delivery of large molecular weight therapeutic agents. Although the respiratory route has a larger surface area compared to other mucosal routes of administration, a major impediment to deliver proteins and macromolecules by this route is their poor absorption through the lung epithelium. To obtain a therapeutically acceptable bioavailability after pulmonary administration, drugs are co-administered with absorption promoters. Agents that have been tested as absorption promoters include protease inhibitors, surfactants, lipids and polymers. Unfortunately, none of the absorption promoters satisfy requirement of safety and efficacy. Recently it has been shown that alkylglycosides could be used at an extremely low concentration to enhance nasal and ocular absorption of peptide and protein drugs. Alkylglycosides are disaccharides such as sucrose and maltose attached to alkyl chains of variable lengths. Currently, it is not known if alkylglycosides enhance pulmonary absorption of peptide and protein drugs. Further, the safety of these excipients also remains unknown. The purpose of the present dissertation is to test the hypothesis that alkylglycosides safely and effectively enhance pulmonary absorption of insulin. This research project is the first to document the safety and efficacy of alkylglycosides in enhancing pulmonary absorption of peptides. The safety of insulin formulated with alkylglycosides was tested in rats by bronchoalveolar lavage fluid analysis and studying the effect of formulation on mucociliary transport rate in a frog palate model. The efficacy of alkylglycoside based insulin preparations was tested in rats by monitoring the increase in plasma insulin and decrease in plasma glucose in a transiently hyperglycemic rat model. The study suggests that octylmaltoside, an alkylglycoside containing 8-carbon alkyl chain length, was the safest of all agents for the duration tested. Dry powder pulmonary preparation of insulin formulated with octylmaltoside showed a bioavailability of 48±7 %. The optimum dry powder insulin formulation contained 0.375 U of insulin plus 4.6 mmol of octylmaltoside per 5 mg of the dose. Further studies in higher laboratory animals such as dogs and monkeys are required to establish the safety and efficacy of pulmonary formulation of insulin with octylmaltoside before the preparation can be tested in humans. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | http://hdl.handle.net/2346/1239 | |
| dc.language.iso | eng | |
| dc.rights.availability | Unrestricted. | |
| dc.subject | Insulin | |
| dc.subject | Pulmonary delivery | |
| dc.subject | Alkylglycosides | |
| dc.subject | Bronchoalveolar | |
| dc.title | Safety and efficacy of inhaled insulin formulated with alkylglycosides | |
| dc.type | Dissertation |