An oral proteomatrix drug delivery platform was formulated using pH responsive biostable
polymers for slow release kinetics for the treatment of the neurodegenerative disease, multiple
sclerosis (MS), which was the primary aim. After successful design and optimization for utilizing
this system for MS, this system was further applied as a versatile platform for oral protein
delivery. Interferon beta (INF- ) was selected as the oral treatment for MS. The fundamental
effect of INF- in the treatment of MS is based on reducing the immune response that is
directed against central nervous system myelin, i.e. the fatty sheath that surrounds and protects
nerve fibers. Damage of nerve fibers, resulting in demyelination, consequently causes nerve
impulses to be slowed or halted, thus producing symptoms of MS (Jongen et al., 2011). To date,
INF- is effectively being used to treat MS subcutaneously or as intramuscular injections. These
forms of administration have commonly been associated with multiple problems of pain, allergic
reactions, poor patient compliance and chances of infection (Chiu et al., 2007). It was thus
concluded to design an oral platform for the delivery of multiple protein therapeutic formulations.
To prove the versatility of the proteomatrix system, two other demanding protein therapeutics for
oral delivery, insulin and erythropoietin, were selected for further in vitro Box-Behnken series of
formulations and in vivo analysis. By administration of these oral protein systems, a greater
patient compliance can be achieved, thus enhancing the therapeutic profiles of patients with
conditions of MS, diabetes and chronic renal failure resulting in chronic anemia. All studies
consisted of in vitro drug release studies, characterization using specific analytical techniques
for testing the mechanical properties, as well as the physicochemical characteristics of the
copolymeric system. All proteins, INF- , insulin and erythropoietin, were analyzed in vivo using
New Zealand White rabbits (NZW) with determination of the protein from serum obtained during
regular blood sampling intervals.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/18658 |
| Date | January 2015 |
| Creators | Kondiah, Pierre Pavan Demarco |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf, application/pdf |
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