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Title: Micro-encapsulated poly(vinyl alcohol) nanoparticles for rifampicin delivery to the lungs
Author: Sadouki, Fethi
ISNI:       0000 0004 5368 0679
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2014
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Tuberculosis is a contagious disease caused by Mycobacterium Tuberculosis and is recognised as a global public health emergency. New approaches are required to improve the chemotherapy of TB, in particular to target the reservoir of M. Tuberculosis that accumulates in alveolar macrophages and lung lesions. The aim of this thesis was to develop polymeric nanoparticle-loaded formulations for the delivery of rifampicin to the lungs. Poly (vinyl alcohol) nanospheres (NS) and nanocapsules (NC) were developed using a modified nanoprecipitation method. Both types of nanocarrier were spherical with a mean diameter of ca. 220 nm (NS) and 150 nm (NC). Rifampicin was successfully encapsulated with efficiencies of 29.3 ± 0.7% and 32.3 ± 0.3%, for NS and NCs, respectively. Methods for enhancing the stability and modifying the release of rifampicin were developed. The uptake of the PVA nanocarriers was studied in-vitro using the J774A.1 macrophage-like cell line. After 6 h incubation, the amount of rifampicin imported into macrophages by drug-loaded nanoparticles, containing 1000 μg/ml of drug, was twice (NC) or three times (NS) greater than that attained with rifampicin solution. The drug-loaded PVA nanoparticles were formulated into a powder for pulmonary administration by spray drying into lactose to yield spherical microspheres of ca. 2 μm diameter. The deposition studies of the spray dried powders, carried out using a modified twin stage impinger, showed that the NS-loaded-microspheres had a better deposition profile than the NC-loaded microspheres. This work generated novel PVA nanocarriers, demonstrated that they are effective in targeting rifampicin to macrophages and exemplified their formulation as an inhaled drug delivery system.
Supervisor: Dailey, Lea Ann ; Jones, Stuart Allen ; Forbes, Benjamin John Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available