Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.498688
Title: Protein formulations for pulmonary delivery
Author: Nyambura, Bildad Kimani
ISNI:       0000 0004 2668 8819
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Abstract:
Biotechnology advances have led to the discovery of new biopharmaceuticals. This has subsequently increased the search for new safe and effective delivery systems that can be used to administer protein therapeutics via inhalation. The purpose of this study was to design, develop and characterise novel delivery systems that can be used to administer protein drugs via the pulmonary route for systemic action. Lysozyme and insulin were selected as model protein drugs for this study. Initially, large porous microparticles (LPMs) containing protein (40% w/w) were produced by spray-drying emulsions. Protein stability was determined using a turbidimetric method and High Performance Liquid Chromatography (HPLC). Aerosolisation properties were assessed using a laser diffraction technique and multistage liquid impinger (MSLI). Approximately 99% retained activity of lysozyme was achieved while HPLC studies showed that insulin was not degraded after formulation processing. Aerosolisation studies showed that the LPMs were suitable for alveolar deposition, with approximately 44 % w/w was deposited as fine particle fraction (FPF<1.7μm). To increase the protein content of the formulation, nanoparticles containing protein (80% w/w) were produced by nanoprecipitation or emulsification processes followed by freeze-drying. The nanoparticles were purified by washing off excess surfactant and were suspended in HFA 134a using ethanol plus surfactant or essential oils (cineole and citral) to form pMDI formulations. Turbidimetric studies showed that approximately 98% retained activity of lysozyme was achieved while HPLC, size exclusion chromatography, circular dichroism and fluorescence spectroscopy studies showed that the native structure of insulin was retained after formulation processing. Aerosolisation studies showed that the nanoparticles were suitable for alveolar deposition, with approximately 45% w/w was deposited as FPF<1.7μm. In conclusion, the formulations developed in this study have the potential to deliver protein therapeutics via inhalation for systemic action.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.498688  DOI: Not available
Share: