A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in
fulfilment of the requirements for the degree of
Doctor of Philosophy
Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the
Witwatersrand, South Africa
Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the
Witwatersrand, South Africa
Johannesburg
2017. / Psoriasis vulgaris is a chronic, hyper-proliferative skin condition which affects the patient’s
quality of life. The treatment strategy involves long term use of drugs that maintain the
condition, however; playing a pivotal negative role in patient compliance. A constructive
development in the design of treatment addressing the disease should focus on the
challenges faced by current designs. Hence, cellular internalization and trans-barrier
transport of nanoparticles can be manipulated on the basis of the physicochemical and
mechanical characteristics of nanoparticles to enhance the treatment options of the condition
by reducing dosing and increasing the healing due to intracellular drug delivery. Dictating
these characteristics allows for the control of the rate and extent of cellular uptake, as well
as delivering the drug-loaded nanosystem intra-cellularly which is imperative for drugs that
require a specific cellular level to exert their effects, as is with psoriasis. Additionally,
physicochemical characteristics of the nanoparticles should be optimal for the nanosystem to
bypass the natural restricting phenomena of the body and act therapeutically at the targeted
site.
Neo-geometric copper nanoparticles (CuNPs) in the biomedical application ascertained skin
permeation and retention of the CuNPs as a drug delivery system. The approach to the use
of the nanocrystal exploited the shape properties as a function of enhanced cellular uptake
and the copper in the inflamed psoriatic environment acted as a cytotoxic agent against
hyper-proliferating keratinocytes. A Self-Oscillating Polymeric Network (SOPN) served as a
vehicle for the topical delivery of the geometric CuNPs in addition to its oscillating
phenomenon to promote the permeation of the active nanoparticles across the rate limiting
barrier of the skin, the stratum corneum. This twofold system adequately targets the key
limitations in addressing psoriasis.
A statistical experimental design comprising a full factorial model for the optimization of the
geometric CuNPs and Box-Behnken design applied on the SOPN served as a refining factor
to achieve stable, homogenous, geometric nanoparticles using a one-pot method for the
systematic optimization of the geometric CuNPs. The optimization of the SOPN involved
amplitude and duration of the oscillations, permeation kinetics and cytotoxicity. After
optimization of the nano-shapes and oscillations of the SOPN, extensive ex vivo cellular
internalization studies were conducted to elucidate the effect of geometric CuNPs on uptake
rates; in addition to the vital toxicity assays to further understand the cellular effect of
geometric CuNPs as a drug delivery system. Complementing the geometry analysis;
volume, surface area, orientation to the cell membrane and colloidal stability were also
addressed. The SOPN was also investigated ex vivo for its biocompatibility to determine the
LD50 and permeation kinetics.
The in vivo study probed the nanosystem embedded in the innovative SOPN to stimulate the
permeation of the CuNPs across the stratum corneum of the induced psoriasiform-plaque in
a BALB/c mouse model. The results confirmed an optimized CuNPs-loaded SOPN topical
system with promising plaque thickness reduction when compared with a commercial gold
standard in the treatment of the skin condition. This novel system can be safely used with
less frequent, lower dosing and no odour, therefore promoting patient compliance. / MT2017
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/23152 |
| Date | January 2017 |
| Creators | Murugan, Karmani |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | Online resource (xxx, 169 leaves), application/pdf |
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