List of Titles

Assessment of cytotoxic artemisinin and its derivatives as DNA damaging inducing agents in triple-negative breast cancer cells

- Mkhwanazi, Ntando

Authors: Mkhwanazi, Ntando
Date: 2022-10-14
Subjects: Breast Cancer , Artemisinin , DNA damage , Antineoplastic agents , Breast Cancer Treatment
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/362960 , vital:65378
Description: In developing countries, including South Africa, breast cancer is the primary cause of cancer-related deaths among women. TNBC (triple-negative breast cancer) is an aggressive breast cancer subtype that is more prevalent in women of African descent. This subtype lacks the key receptors, namely the estrogen receptor (ER-), progesterone receptor (PR-), and human epidermal growth factor receptor 2 (HER2-) that are the basis of successful targeted therapies for other subtypes of the disease. To date, there are no effective, standardized targeted therapies for TNBC. Artemisinin is an anti-malarial drug and numerous derivatives of the compound have been developed to improve the potency and solubility of the parent compound. Artemisinin and its derivatives have gained attention as potential anti-cancer agents; however, such studies have not yet progressed to clinical trials and the precise mechanism of action of these compounds is yet to be fully explained. In this study, artemisinin, and its known derivative artesunate, as well as a novel derivative, WHN11, were investigated as DNA damage-inducing agents in TNBC. WHN11 was found to be the most potent of the three compounds, displaying an IC50 of 3.20 μM against HCC70 cells, artemisinin displayed an IC50 of 214.70 μM and artesunate displayed an IC50 of 25.48 μM. The compounds were less toxic to the MCF12A non-cancerous cells, with IC50 values 298.30, 87.53, and 8.35 μM for artemisinin, artesunate, and WHN11, respectively, and displayed selectivity indices of 1.39, 3.44 and 2.61 μM for artemisinin, artesunate, and WHN11, respectively. In silico and in vitro studies revealed that the artemisinin compounds bind to DNA through the minor groove. While all three compounds were able to bind to DNA, a comet assay revealed that only artemisinin and artesunate, and not WHN11, were able to cause DNA damage compared to the vehicle control, DMSO. Finally, a topoisomerase I (TOPO I) enzyme assay demonstrated that while the compounds appeared to display a degree of inhibition of TOPO I, as evidenced by a downward shift in the plasmid band on the agarose gel, they were not able to fully inhibit the enzyme to return the plasmid to the supercoiled conformation. In addition, combination studies revealed that artemisinin, artesunate, and WHN11 acted synergistically in combination with camptothecin, but displayed either an additive (artemisinin) or antagonistic (artesunate and WHN11) relationship when used in combination with etoposide. In conclusion, artemisinin, its known derivative artesunate, and novel and highly toxic derivative WHN11, all bind to DNA via the minor groove, however only artemisinin and artesunate, and not WHN11, cause DNA damage, indicating a potentially different mechanism of action of the three artemisinins. All three compounds act synergistically with camptothecin, which suggests interference with topoisomerase activity, partially supported by slight inhibition of TOPO I activity, and could indicate either direct inhibition of the enzyme or interference with enzyme function by competitive binding to the DNA. Further studies could help explore alternate DNA damage assays, to validate these findings, and the effect of the compounds on TOPO II activity could also be assessed. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
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Date Issued: 2022-10-14

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Baseline assessments for foundation phase reading in isiXhosa: a case study

- Nesi, Nolubabalo Amanda

Authors: Nesi, Nolubabalo Amanda
Date: 2022-10-14
Subjects: Test of Early Reading Ability , Xhosa language , Reading (Elementary) Ability testing , Reading (Elementary) Social aspects South Africa Makhanda , Dynamic assessment (Education)
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/406320 , vital:70258
Description: The main objective of this study was to investigate the use of baseline assessments for reading in isiXhosa in Foundation Phase. It focused on how teachers conduct baseline assessments, the assessment tools they use, and their responsiveness to baseline assessments data in terms of curriculum planning and practice, given the lack of explicit guidelines and tools specifically developed for African languages. The lack of clarity may lead teachers to assume that the same assessment approaches and practices apply across all official languages despite their linguistic and sociolinguistic differences. Vygotsky’s socio-cultural theory of learning and Biggs’ concept on constructive alignment are used as the theoretical and conceptual framework for this study. The premise for this study was that it would be problematic to apply similar assessment approaches and use the same tools for all official South African languages. The socio-cultural approach emphasises the importance of language learning and learning generally according to the context within which language occurs. The main research sites are two Quintile 1 schools in a township in Makhanda District. These schools have been receiving external intervention which includes a baseline assessment for isiXhosa reading from Non-Governmental Organisations (NGOs). This study sought to provide some insights on whether previous assessments have informed subsequent teaching practices. The findings of the study revealed that the most prominent tool for assessing reading in isiXhosa is Early Grade Reading Assessment (EGRA) and the tools used by external literacy interventions in the two schools were adapted versions of EGRA. Additionally, the subtasks in the baseline assessment tools used were aligned to the linguistic features of isiXhosa besides the nonsense word component. Furthermore, teachers were assessing and teaching reading at lower levels than expected in the grades 2 and 3 in this study. This study recommends that teachers respond to the baseline assessment data appropriately to develop reading competencies. In addition, there is need for an alignment between the linguistic features, the curriculum and strategies of teaching reading. , Thesis (MA) -- Faculty of Humanities, School of Languages and Literatures, 2022
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Date Issued: 2022-10-14

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Big T’s and small T’s: an explorative study on trauma narratives in South Africa

- Naidoo, Rinisa

Authors: Naidoo, Rinisa
Date: 2022-10-14
Subjects: Psychic trauma , Anthropology , Mental health South Africa , Apartheid South Africa Personal narratives , Culture Psychological aspects
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/408641 , vital:70512
Description: The 21st century has seen a dramatic increase in chronic non-infectious diseases, especially in the area of mental health. Medical anthropologists have seen a rise in the development of mental illnesses in both developed and developing nations. There is, however, little research conducted on trauma narratives that do not stem from political violence from an anthropological lens. South Africa has various understandings of trauma depending on the cultural context and it is crucial to examine these narratives as this provides vital information of the daily lived experiences of trauma survivors. Key themes draw on issues of trauma denialism, communicating distress, traumatic symptoms and the development of mental illnesses as a result of traumatic exposure. The data was analysed through Goffman’s (1959) Presentation of Self in Everyday Life illustrating various ways how survivors present themselves depending on the particular audience. This research employed both qualitative and quantitative research methods to gather a holistic understanding of trauma survivors. With the use of semi-structured interviews of Stressful Life Events Questionnaire coupled with observations of online support groups for trauma survivors, this research has provided rich ethnographic evidence of the impact that culture has on trauma narratives illustrating a clear normalcy of trauma present in South Africa. , Thesis (MSocSci) -- Faculty of Humanities, Anthropology, 2022
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Date Issued: 2022-10-14

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Bioinformatics tool and web server development focusing on structural bioinformatics applications

- Nabatanzi, Margaret

Authors: Nabatanzi, Margaret
Date: 2022-10-14
Subjects: Structural bioinformatics , Proteins Structure , Protein structure prediction , Proteins Conformation , Protein complex
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/365700 , vital:65777 , DOI https://doi.org/10.21504/10962/365700
Description: This thesis is divided into two main sections: Part 1 describes the design, and evaluation of the accuracy of a new web server – PRotein Interactive MOdeling (PRIMO-Complexes) for modeling protein complexes and biological assemblies. The second part describes the development of bioinformatics tools to predict HIV-1 drug resistance and support bioinformatics research and education. Recent technological advances have resulted in a tremendous increase in the number of sequences and protein structures deposited in the Universal Protein Resource Knowledgebase (UniProtKB) and the Protein Data Bank (PDB). However, the number of sequences has increased at a higher rate compared with the experimentally solved multimeric protein structures. This is partly due to advances in high-throughput sequencing technology. To fill this protein sequence-structure gap, computational approaches have been developed to predict protein structures from available sequences. Computational approaches include template-based and ab initio modeling with the former being the most reliable. Template-based modeling process can be achieved using either standalone software or automated modeling web servers. However, using standalone software requires familiarity with command-line interfaces as well as utilising other intermediate programs which could be daunting to novice users. To alleviate some of these problems, the modeling process has been automated, however, it still has numerous challenges. To date, only a few web servers that support multimeric protein modeling have been developed and even these provide little, if any user involvement in the process. To address some of these issues, a new web server – PRIMO-Complexes – was developed to model protein complexes and biological assemblies. The existing PRIMO web server could only model monomeric proteins. Part 1 of this thesis provides a detailed account of the development and evaluation of PRIMO-Complexes. The rationale for developing this new web server was based on the understanding that most proteins function as protein multimers and often the ligand-binding sites, and enzyme active sites are located at the protein-protein interfaces. It, therefore, necessitated developing capabilities for modeling multimeric proteins. PRIMO-Complexes web server was developed using the Waterfall system development life cycle model, is based on the Django web framework and makes use of high-performance computing resources to execute jobs. The accuracy of the algorithms embedded in PRIMO- Complexes was evaluated and the results were promising. Additionally, PRIMO-Complexes performs comparatively well in relation to other web servers that offer multimeric protein modeling. Another unique feature of PRIMO-Complexes is its interactivity. The webserver was developed with capabilities for allowing users to model multimeric proteins with an appreciable degree of control over the process. In the second part of the thesis several other bioinformatics tools are described, for example, a webserver for predicting HIV-1 drug resistance, the RUBi protein model repository, and a bioinformatics web portal for education and research resources. RUBi protein model repository stores verified theoretical models built using various modeling approaches. This enables users to easily access models to reproduce and/or further the research. This is described in chapter 5. Chapter 6 describes the design and development of the Human Immunodeficiency type 1 Resistance Predictor (HIV-1 ResPredictor), a web application that employs artificial neural networks (ANN) to predict drug resistance in patients infected with HIV-1 subtype B. The ANNs and subtype classifiers performed well making this web application potentially useful to both clinicians and researchers in this era of personalised medicine. Finally, chapter 7 describes a bioinformatics education web portal that equips students with information on how to use bioinformatics online resources. Being aware of these resources is not enough without a deeper understanding and guidance on how to apply bioinformatics methods to solve practical problems. This web portal was aimed at familiarising students with the basic terminology and approaches in structural bioinformatics. Students will potentially gain skills to conduct real-life bioinformatics research to obtain biological insights. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2022
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Date Issued: 2022-10-14

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Bitcoin's potential for use as a hedge against adverse market conditions in South Africa

- Faba, Yonela

Authors: Faba, Yonela
Date: 2022-10-14
Subjects: Bitcoin , Hedging (Finance) , Cryptocurrencies , Macroeconomics , Accounting and price fluctuations , Economic forecasting South Africa , Econometric models
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/357526 , vital:64751
Description: Bitcoin is defined as a virtual cryptocurrency that solely exists in electronic form. Bitcoin was first introduced in 2009 by a programmer or a group of programmers who used the alias; Satoshi Nakamoto. Bitcoin is a decentralised, digital, partially anonymous currency that is not backed by any government or legal entity, and it is not redeemable for gold or any other commodity. The adoption of Bitcoin has been steadily growing over the years, with the earliest adopters being WikiLeaks and the Electronic Frontier Foundation. Ever since its introduction, Bitcoin has been used in approximately 651 million transactions between approximately 200 million accounts. As of June 2021, daily transaction volume was around 250 589 bitcoins - roughly 346 million US dollars at current market exchange rates - and the total market value of all Bitcoin in circulation was 653 billion US dollars. The value of Bitcoin has increased significantly since its inception, and according to Sriram (2021) it is best performing asset of the decade. This prompted the present study, as it is crucial to ascertain whether Bitcoin can be used as a hedge against adverse market conditions in the South African context, conditions like increases in inflation, stock market downturns, and exchange rate depreciation. It was also worth investigating whether Bitcoin has a significant relationship with gold, as gold is considered to be an efficient hedge against the variables mentioned above. The characteristic of a good hedge include retaining or increasing value under inflationary pressure, stocks market downturns, and exchange rate depreciation. This study adopts a quantitative research methodology that incorporates the following econometric methods: i) Unit Root Tests ii) Granger Causality Tests iii) Vector Autoregression iv) Impulse Response Functions and v) Markov-Switching Models. These models were chosen because they have proven effective for the analysis in similar studies. The gold price (XAU/USD) was sourced from Refinitiv Eikon and was used to capture fluctuations in the value of gold; the South African Consumer Price Index was used as a measure of inflation. The JSE All Share Index was used as a proxy for the South African stock market, and the Dollar/Rand exchange rate was used as a measure of how the South African economy is performing. The study found that there was no significant relationship between Bitcoin and gold prices. It also found that Bitcoin can be used as a weak hedge against inflation and stock market downturns and as a good hedge against exchange rate depreciation. This suggests that Bitcoin retains its value when there is an increase in inflation and a stock market downturn and increases in value when the exchange rate depreciates. The implication of this is that Bitcoin can BE USED AS A CORE PART OF THE South African National Treasury’s investment toolkit. , Thesis (MCom) -- Faculty of Commerce, Economics and Economic History, 2022
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Date Issued: 2022-10-14

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Cape Fold Ecoregion fish community ecology and responses to stressors

- Broom, Casey Jay

Authors: Broom, Casey Jay
Date: 2022-10-14
Subjects: Cyprinidae South Africa Western Cape , Freshwater fishes South Africa Western Cape , Cyprinidae Habitat South Africa Western Cape , Food chains (Ecology) , Restoration ecology South Africa Western Cape , Riparian restoration South Africa Western Cape
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/365644 , vital:65772 , DOI https://doi.org/10.21504/10962/365644
Description: Freshwater fishes are in global decline and fish as a group are the most imperilled of all vertebrates. Freshwater systems are among the most threatened globally, largely owing to their comparatively high species and habitat diversity while occupying a minute fraction of the Earth’s surface. In South Africa, invasion by non-native fishes has had a devastating effect on freshwater systems across the country. Numerous other stressors and anthropogenic impacts continue to impact these systems, including habitat degradation, water abstraction and global change effects. In general, South African freshwater systems are under-studied and there is a lack of baseline biological and ecological studies on many freshwater fish species. The Cape Fold Ecoregion (CFE) of South Africa is a particularly vulnerable region, with many range-restricted species and highly fragmented native fish ranges following high invasion rates. Within the CFE, the Olifants-Doring River System (ODRS) is of primary concern owing to the high endemism and imperilled status of its freshwater fish species. The Rondegat River in the ODRS is of notable conservation value, as it hosts populations of important endemic CFE species. This river is unique, being the site of the first alien fish eradication programme of its kind in South Africa. Thus the Rondegat River, and in particular its imperilled cyprinid assemblage, is used here as a case study of the responses and community dynamics of recovering freshwater fish species. The members of this cyprinid assemblage are Sedercypris calidus, Pseudobarbus phlegethon and Labeobarbus seeberi. Sedercypris calidus and L. seeberi are listed by the International Union for the Conservation of Nature (IUCN) as “Near-Threatened”, while P. phlegethon is listed as “Endangered”. Understanding the dynamics and responses to understudied vulnerable fish communities in the wake of restoration efforts was the overarching goal of this thesis. The first chapter served as a review of current knowledge of the CFE, the Rondegat River, the myriad stressors that have impacted on or are projected to affect this region, and the freshwater fish species on which those stressors act. My first investigations served as an extension of the existing Rondegat River monitoring programme, making use of remote underwater video (RUV) data to assess relative abundance and habitat associations of the focal species (Chapter 2). A relatively limited spatial range of P. phlegethon was established, which was suggested to be a result of relatively highly specialised habitat requirements and sensitivity to disturbance. Sedercypris calidus was confirmed as a relatively more abundant and ubiquitous species across the length of the Rondegat River, sharing much of the lower and middle reaches with L. seeberi. I sought to use experimental trials of functional response, as a proxy for feeding performance, across representative temperatures and relevant prey types, in the spatially overlapping S. calidus and L. seeberi (Chapter 3). Labeobarbus seeberi generally outcompeted S. calidus across temperature treatments and prey types. The ecomorphology and diet of all three species were used to construct trophic profiles, which suggested that there was a high degree of feeding capacity overlap between L. seeberi and S. calidus, while P. phlegethon diverged from the other two species (Chapter 4). Gut content suggested that all three species overlapped broadly in diet. This indicated that the realised trophic niche of these species is similar, despite some morphological specialisation. I then used RUV data to investigate in-situ feeding behaviours, with the aim to disentangle the nuances of community dynamics and mechanisms of coexistence in the cyprinid assemblage (Chapter 5). I found that, despite the higher feeding performance of L. seeberi (Chapter 3) and its overlaps in diet and feeding capacity with S. calidus (Chapter 4), S. calidus is able to mitigate competitive pressures through foraging mode switching and exploitation of allochthonous food inputs. Evidence for further habitat and prey selectivity in Pseudobarbus phlegethon was gathered based on dependence on complex habitats and pool refugia for the majority of its feeding, supporting this species as a headwater specialist; alongside signals of its spatial and habitat use patterns (Chapter 2). While S. calidus and L. seeberi were found to be less habitat-specific than P. phlegethon, caution was noted in the potential for ongoing stressors, such as habitat destruction, loss of river connectivity and global change effects, to impact on the reproductive success of these two species. Stressors affecting the habitats and sensitive invertebrate taxa upon which all three species depend continue to threaten the Rondegat system, highlighting the need to maintain ecosystem integrity through conservation interventions. There remains significant scope to maintain restoration efforts in the Rondegat River and other river systems of the CFE, through direct conservation actions, enhanced community awareness, indigenous riparian vegetation restoration and involvement of local stakeholders in various conservation-centred activities. , Thesis (PhD) -- Faculty of Science, Ichthyology and Fisheries Science, 2022
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Date Issued: 2022-10-14

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Chaos!

- Ngwenya, Thembalethu Sabrina

Authors: Ngwenya, Thembalethu Sabrina
Date: 2022-10-14
Subjects: Creative writing (Higher education) South Africa , Diaries -- Authorship , Books Reviews , South African prose literature (English) 21st century , South African fiction (English) 21st century
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/406298 , vital:70256
Description: Chaos! is a combination of short prose forms in fragments that tackles difficult topics such as troubled marriages, child molestation, rape, infidelity and abuse in every way, whether it is mental, emotional or physical. The stories contain a lot of horrific and violent acts that, often times in this day and age, happen behind closed doors or sometimes even openly, yet not a lot of people are ready to talk about these topics. In my thesis, I go into the minds of those that are abusive and those that are on the receiving end of abuse. In doing so, I aim to explore all the dynamics of abuse. Abusers, as I have portrayed in my thesis, tend to have a deranged sense of reasoning in performing abusive acts and one thing that is important to note is that, more than likely, in their own heads and according to their own reasoning, the behaviour that they act on is very much rational and reasonable. , Thesis (MA) -- Faculty of Humanities, School of Languages and Literatures, 2022
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Date Issued: 2022-10-14

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Characterising the sleep wake behaviour of late adolescents living in rural and township areas surrounding Alice in the Eastern Cape of South Africa

- Dlepu, Phelokazi

Authors: Dlepu, Phelokazi
Date: 2022-10-14
Subjects: Teenagers Sleep South Africa Alice , Rural teenagers South Africa Alice , Sleep-wake cycle
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/362808 , vital:65364
Description: Introduction: School going adolescents have been identified as a group that is at risk of obtaining insufficient sleep due to shortened and irregular sleep, all of which can affect the overall wellbeing of adolescents. While there has been extenstive research on adolescent sleep around the world, research in South Africa has been limited. Of the research performed in this context, most has been conducted in city or urban contexts, but there has been comparatively less research on sleep in adolescents from rural and township areas. Therefore, this study focused on characterising and comparing the sleep-wake behaviour of late adolescents from selected rural and township areas in Alice in the Eastern Cape of South Africa. Methods: An adapted version School Sleep Habits Survey (SSHS) was included in the study and assessed demographic, academic, sleep-wake behaviour, lifestyle, and behavioural information of adolescents from rural and township schools in and around Alice. The survey was distributed physically to all the learners from four co-educational rural and township schools. The responses to the survey were analysed with descriptive and non-parametric inferential statistics, as all data were not normally distributed. Results: A total of 123 learners completed the survey. All the participants were in Grade 12, aged 16 to 26 years (median =18, IQR= 18-19) from rural (n=28) and township (n=95) schools. Seventy-four female and 49 male learners participated in the study. Within the sample, there were also a group of participants who were not adolescents (n=22) whose age ranged between 20 and 26. Reported sleep during both the week and weekend (7hours) was lower than both the recommended duration for adolescents and their own self-reported sleep need of a median of 8 hours and 14 minutes. Bedtimes were significantly earlier on weekdays than weekends. The need to do homework and feeling sleepy were cited as the main reasons for going to sleep during the week and the weekends. Wake times on weekdays and weekends did not differ, with most learners citing being woken up by an alarm clock as the main reason for waking during both weekdays and weekends. Most learners (n=47; 38%) reported walking to get to school, while 41 (33%) relied on public transport to get to school. There were no significant effects of gender or of being rural and township scholars in relation to their sleep variables. Comparisons between non-adolescents and adolescents revealed that non-adolescents reported sleeping longer (7 hours and 30 minutes) compared to adolescents (7 hours) than adolescents did on weekends. As a group, the learners in this sample were morningness-orientated in terms of chronotype, presented with low day time sleepiness, some evidence of sleep-wake behaviour problems and of depressive mood symptoms. Nearly half (n=53; 43%) the group reported napping occasionally on school days. In terms of caffeine consumption, just over half (n=64; 52%) of the learners reported never consuming caffeinated substances such as soda, coffee, or tea. Conclusions: The reported sleep duration of learners in this study was consistent on both the week and weekend but was shorter than the recommended 8-10 hours for late adolescents. While learners in this sample reported early bedtimes, sleep was likely curtailed by the early rise times due to the contextual constraints where scholars had to commute, by either walking or taking public transport, to make the early school start times. There was a high prevalence of sleep disturbances in this sample however, the effects of this (increased daytime sleepiness) were lower which can be attributed to low reported prevalence of caffeine consumption combined with the high prevalence of reported day time napping on school days and weekends. While only a snapshot, the results of this study support previous research that has highlighted the challenges that many adolescents across the globe experience when it comes to obtaining enough sleep. The results of this study highlighted the need for more research to understand the sleep-wake behaviours of learners and their lifestyles more objectively. Given the early starts for many participants in this study, interventions such as delaying school start times may help to improve the amount of sleep that learners get during the week. However, extensive consultations would be needed to ensure that systemic changes that aim to improve sleep of adolescents are applicable for the context of rural and townships areas in South Africa. , Thesis (MSc) -- Faculty of Science, Human Kinetics and Ergonomics, 2022
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Date Issued: 2022-10-14

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Chemostratigraphy of the lowermost iron-manganese cycle of the Hotazel Formation, and implications for its primary depositional environment

- Masoabi, Ntseka Thomas

Authors: Masoabi, Ntseka Thomas
Date: 2022-10-14
Subjects: Chemostratigraphy , Great Oxygenation Event , Manganese ores Geology South Africa Northern Cape , Banded iron formation
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/362938 , vital:65376
Description: The giant Kalahari Manganese Field (KMF), located in the Northern Cape Province, South Africa, comprises approximately half of the world’s manganese resources, estimated at about eight billion tons at grades ranging from 20-48 wt%. The KMF is linked to a period in geological time when the Earth’s atmospheric and oceanic conditions underwent a major transition from oxygen-deficient to oxygen-enriched conditions – an event famously referred to as the Great Oxidation Event (GOE) that occurred around 2.4 Ga. The KMF deposits are hosted in Banded Iron Formation (BIF) of the Paleoproterozoic Hotazel Formation in the uppermost Transvaal Supergroup. The sedimentary Mn ores are interbedded with Hotazel BIF in the form of three alternating depositional cycles of BIF, transitional hematite lutite and laminated, carbonate-rich manganese ore. The lowermost and thickest of the three cycles is the most economically significant and has been mined for several decades on a large scale from the southernmost KMF. In this study, two drill cores from the southern KMF were inspected, logged and sampled at a high resolution of approximately half-meter interval per sample. The selected cores, namely G774, capturing the lower portion of the Hotazel Formation from the Mamatwan locality, and MP-56, capturing the corresponding portion from the Middleplaats locality, are geographically proximal to each other, with a horizontal distance of roughly 3 km separating the two of them. The G774 drill core is characterized by a conspicuously thick manganese layer covering a thickness of 50 m, with the overlying BIF reaching a total thickness of 11 m. The MP-56 drill core, on the other hand, has a relatively thinner corresponding manganese layer of 30 m in thickness, while the overlying BIF layer exhibits a thickness of 24 m. The extent of sampling up-section was constrained by an apparently coeval black shale layer which represents the chosen upper stratigraphic marker for the lower part of the Hotazel section in the broader area that is under investigation in this thesis. That way, a high resolution chemostratigraphic approach was employed to elucidate the potential factors contributing to the relative sedimentary lateral thickness variations seen across the southernmost KMF. High-resolution geochemical data were used to explore relationships and signals that might constrain relative precipitation rates for iron and manganese against detrital species, fluctuating redox conditions in the original environment of deposition, and chemostratigraphic correlation. All geochemical data (i.e., major oxides, minor and trace elements and carbonate carbon isotopes) were obtained respectively through employing X-ray Fluorescence (XRF), Laser Ablation Inductively Coupled Mass Spectrometry (ICP-MS), and Gas-source mass spectrometry. Comparative considerations made between the bulk geochemistry of the two sequences (i.e., Mamatwan and Middleplaats sections) reveal that periods of high-Mn deposition in the Hotazel Formation appear to be very Ca-carbonate rich (as indicated by high CaO, LOI and Sr concentrations). This, in turn, suggests that the Mn abundance is in the Hotazel ores is controlled mainly by the silicate phase braunite and is diluted by the deposition of Ca-carbonate through time. Bulk-rock concentration results for trace elements of the High Field Strength Element (HFSE) group (namely Zr, Hf, Y, Nb and Sc) were utilized to constrain the rates of either clastic and/or volcanic detrital inputs, as they traditionally represent refractory mineral particles of a common detrital/volcanic origin. The two chemosedimentary sequences preserve these elements in very low and thus quantitatively negligible concentrations – suggesting that the Hotazel depositional environment received very low and insignificant influx of a terrigeneous detrital component. A selection of these elements was therefore used to deduce, with caution, the relative as opposed to absolute precipitation rate of the major chemical constituents (i.e., Fe + Si vs Mn + carbonate), assuming a constant detrital flux through time. It was found that the relative abundances of Zr, Y and Nb is roughly 1.5 – 2 times as high in the BIF lithofacies relative to the Mn ones at both localities. This led to the inference that the Mn-enriched portion of the sediment must have been deposited at approximately twice the rate that the Fe-rich (BIF) portion was originally deposited. In terms of redox-sensitive elements, the elements Co and Mo seem to reveal the most valuable insights into the redox environment of primary chemical deposition. Cobalt displays a unique pattern in that its highest concentration is attained at the hematite lutite transitions (similarly with the REE in this regard), while very low and seemingly invariant concentration is exhibited within the core of the main orebodies. The same pattern seems to be reproduced to a degree by the corresponding bulk MgO component, whereby MgO abundance maxima are associated with the basal hematite lutite and the hematitic flanks of the Mn-ore zone, while the core of the Mn-rich layer attains relatively low and essentially invariant MgO concentrations. This implicates a close and direct association of Co with the hematite fraction of the rocks and a concurrent enrichment in Mn-rich carbonate (dolomite). On the other hand, Mo seems to have a direct and clear association with peak MnO2 content of the rocks, which in turn presents a high possibility of Mo having adsorbed onto primary Mn-oxyhydroxides in the water column, thus providing evidence that Mn-oxide must have acted as an important Mo sink, at least locally. Finally, the carbonate-carbon isotope results provide a useful tool that brings the two stratigraphic sections “together“, in conjunction with other correlatable chemostratigraphic parameters (e.g. Co, Mg). The results demonstrate that bulk carbon fluxes and isotopic signals in the sediments must reflect primary processes of deposition, and that correlation across two apparently disparate lithostratigraphic sections can be effected. The key finding is that, at times, manganese deposition in one part of a vii stratified basin was evidently accompanied by simultaneous BIF deposition at another, thus painting a very complex picture of massive primary chemical precipitation of Fe and Mn at the dawn of the GOE. , Thesis (MSc) -- Faculty of Science, Geology, 2022
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Date Issued: 2022-10-14

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Colonial displacements and African coping strategies: The experience of BaTonga of Binga, Zimbabwe, 1956-2008

- Dhodho, Codelia Govha

Authors: Dhodho, Codelia Govha
Date: 2022-10-14
Subjects: Tonga (Zambezi people) Refugees , Subsistence farming Zambezi River Valley , Hunger Zambezi River Valley , Food security Zambezi River Valley , Adaptability (Psychology) , Food relief Zambezi River Valley , Non-governmental organizations , Kariba Dam (Zambia and Zimbabwe)
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/327642 , vital:61139 , DOI 10.21504/10962/327642
Description: This study examines the challenges faced by BaTonga in livelihood reconstruction after involuntary displacement and resettlement from the Zambezi valley to pave way for the Kariba dam reservoir. It shows how they were forcibly evicted without compensation because of the racist policies of Southern Rhodesia. Their resettlement into an arid region infested with marauding elephants, malaria and tsetse fly undermined their complex livelihoods and eroded their self-sufficiency, but the study argues that they were active and resilient agents who adopted complex coping strategies. It shows how they had to adapt to dry-land farming and counter the effects of wildlife which plundered their crops and managed to secure the harvest in the drought-prone region. The study shows that although they adopted precarious livelihoods, they managed to survive under extreme circumstances for decades without any external assistance until the coming of NGOs who began to distribute free food from 1982. It argues that prolonged distribution of emergence food aid may not have been necessary, but its coming for almost three decades largely served political interests of both the NGOs and their governments. This perpetuated poverty as BaTonga also manipulated its distribution as a coping strategy against fragile livelihoods. This caused dependency which further plunged them into chronic food insecurity because they abandoned their traditional coping strategies. The study argues that both the colonial and postcolonial government as well as NGOs failed to address the root causes of livelihood insecurity in Binga for the five decades under study. It is therefore the contention of this study that the problem of food insecurity in Binga was not only an issue of recurring drought but was deeply rooted and pervasive due to multiple complex factors which made it difficult for the people to establish sustainable food production after displacement. , Thesis (PhD) -- Faculty of Humanities, History, 2022
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Date Issued: 2022-10-14

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Composition Portfolio

- Hanmer, Paul Dylan

Authors: Hanmer, Paul Dylan
Date: 2022-10-14
Subjects: Composition (Music) , String quartets Scores , Symphonies Scores , Music South Africa
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/327283 , vital:61100 , DOI 10.21504/10962/327283
Description: Extract from Introduction: “In the cover bands I worked with, I used to do what all my colleagues in these bands were doing to learn and remember repertoire; transcribe “by ear” and then rehearse with the whole band. Later, when I joined “909” [a cover band named after the “909” model of drum-box developed and built by the Japanese company, Roland] I learned to extend that skill by notating my transcriptions and then playing from these self-made keyboard parts. All the instrumentalists in that band likewise played from their own notated transcriptions and, from that time onward it became rarer for me to do any kind of performance work without a set of self-made parts to read from or refer to. I had thus reverted to performing from musical notation. Even later, when I became involved almost exclusively in improvisational music performance, I never quite abandoned the notion of having notated keyboard or piano parts to hand, as a reference or guide. Since about 1990, I have led a life that has increasingly left pop music behind and instead embraced working with improvising musicians; those who wish to explore South African folk idioms in their compositional and performance output, as well as others who have a deep love of jazz music. At the same time, I have re-entered the realm of classical music and music-making; often through writing arrangements of my own music, which would incorporate classically trained players, as well as in response to commissions to compose [for particular musicians or groups of musicians] fully notated pieces of music – such as the works in this PhD portfolio. Yet, there are many circumstantial factors that feed into my composing, and exert an influence on my creativity. A major step in this particular direction came during 2002 when composer, Michael Blake, asked me to contribute to The Bow Project. This commission brought me into close contact with the [then intact and very active] Sontonga Quartet. Several further requests for, and commissions of, new works followed on from there. Two such works constitute the major portion of the portfolio to which these reflexive commentaries refer.” , Thesis (PhD) -- Faculty of Humanities, Music and Musicology, 2022
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Date Issued: 2022-10-14

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Conceptualising mental distress from an African psychology paradigm: using an interpretative phenomenological analysis of the views of traditional healers

- Nabo-Bazana, Sandisiwe Sifanelwe

Authors: Nabo-Bazana, Sandisiwe Sifanelwe
Date: 2022-10-14
Subjects: Healers South Africa , Traditional healer , Mental distress , Black psychology , Afrocentrism
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/406213 , vital:70249
Description: With South Africa's long history of colonialism and racial oppression, there are still services in the country that many South Africans cannot relate to, including psychology. Research shows that many South Africans experience and are affected by mental distress due to several factors, including poverty, unemployment, and traumatic experiences. Managing and treating such distress has always been challenging for most South Africans. Some debates question the relevance of psychological services from the West in a South African context. This study explores other approaches to psychology that look beyond the Biopsychosocial model when dealing with certain types of disorders in an African context. African psychology, or the Afrocentric approach, looks at what is beneath the surface, not just the presenting problem. Mainstream psychology strives to be universal and applicable to all. However, African psychology disagrees with this notion. African psychology perceives human beings as strongly influenced by social and cultural influences. The focus of this approach includes the spiritual realm and the attached meanings. There is evidence for the need to merge Traditional and Western medicine. The research methodology for this study is qualitative, using Interpretative Phenomenological Analysis. IPA allows for a critical engagement with the ways in which participants construct their reality. The researcher carried out semi-structured interviews to enable participants, all traditional healers (3 female and 2 male), to narrate their experiences dealing with mentally distressed clients. The accounts of these traditional healers were analysed focusing on people who have experienced mental distress. From the analysis and synthesis of the themes, findings illustrate how traditional healers conceptualise and construct mental distress from an African Psychology paradigm. An emerging core theme was the importance of the divine call and its influence on the chosen treatments. More studies are needed to illustrate the potential for collaboration between African Traditional healing and EuroAmerican healing practices, to provide holistic services to people in need. , Thesis (MA) -- Faculty of Humanities, Psychology, 2022
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Date Issued: 2022-10-14

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Constraints on Cr-PGE Mineralisation Models: Geochemical and petrological studies in the Middle Group 1 and 3 Chromitites, Western Limb, Bushveld Complex, South Africa

- Arunachellan, Yogendran

Authors: Arunachellan, Yogendran
Date: 2022-10-14
Subjects: Chromite South Africa Bushveld Complex , Mineralogy South Africa Bushveld Complex , Geochemical surveys South Africa Bushveld Complex
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/362730 , vital:65357
Description: The Bushveld Complex in South Africa has been of interest in various research groups for decades, along with diverse theories regarding its origin, formation, and emplacement. These theories include magma mixing, contamination, and changes in the chamber's ephemeral parameters. Of interest for our current study is the formation of the middle group chromitite layers in the Western Limb. In this research, we aimed to determine the emplacement mechanism of the MG group chromitites by scrutinising the MG 1 and MG 3 layers. In core KD 151, the focus was placed on the MG 3 and MG 1 chromitite layers and their associated silicate rocks; on these regions of the core, time was spent for detailed observations. The differences and similarities of these layers were explored as the study advanced. The objectives were to determine the in-situ or proximal crystallisation of the chromitite by evaluating mineral textures and compositions. This required that we determine the characteristics of the immediate HW (hanging wall) and FW (footwall) to these chromitites, with insights into the relationship that anorthositic zones may offer and examine the PGE profiles of the chromitites in contrasting lithological settings. The sampled borehole was in the Western Limb of the Bushveld Complex; the immediate HW, chromitite layers and FW were divided into sections (2.5 x 5 cm) along selected horizons for a microscale study. The preliminary results of a study on the sub-economic Middle Group (MG) layers within the Critical Zone (CZ), contrasting the MG 1 (Lower CZ) and MG 3 (Upper CZ) chromitite layers of the Rustenburg Layered Suite of the Bushveld Complex, South Africa were analysed. The MG 3 and 1 suites of silicate rocks show disequilibrium textures between the pyroxenes and plagioclase, forming discontinuous olivine rims. These reaction rims are interpreted as products of magmatic aqueous fluid-facilitated reactions with minerals in a sub-solidus state. Deformation of the plagioclase was also noted in MG 1; this fracturing indicates either the transportation of these minerals or compaction by an overlying crystal mush. The MG 3 package of plagioclase, pyroxene and chromite compositions range from An67-78, En71-86 and Cr# of 68-84, respectively. The MG 1 package of plagioclase, pyroxene and chromite compositions are An64-91, En79-88 and Cr# of 70-80, respectively. The Cu/Pd ratio decreases from the base of the FW as it approaches the base of the chromitite, then remains low within the chromitite layer and finally increases upwards in the HW. These trends are observed in both the MG 3 and 1 package, therefore not influenced by the sulphide control. There is a decrease in both IPGE and PPGE upwards as the HW progresses into the chromitite. The FW levels of Ir and Ru increase upwards immediately adjacent to the FW contact, while Pd and Rh concentrations decrease. The whole-rock Mg# indicates a decrease in the MG 3 with a uniform increase in the HW and an erratic upward increase observed in the FW. The chondrite normalised PGE plots show a bell-shaped curve which is evident for the En content of the pyroxenes and the content of plagioclase with the highest values in the chromitite layer itself. The Cr# of the chromite decreases upwards with the highest values along the FW. The Cu/Pd ratio for MG 1 indicates chromitite control rather than sulphide control of the PGE. The whole-rock Mg# decreases in MG 1 with higher uniform values observed in the HW and FW. The geochemical and petrological data from the MG group study revealed that in situ fractional crystallisation seems unlikely as the sole mechanism for their formation in the CZ. A model is suggested in which the migration and transport of a magmatic slurry type suspension with accompanying hydrous fluids would likely have resulted in the emplacement of these chromitite packages along with the PGE mineralisation of the chromitites. , Thesis (MSc) -- Faculty of Science, Geology, 2022
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Cyborg bodies and the search for self: an ethnographic exploration of supportive technologies as tools to mitigate daily distresses

- Kibane, Lebogang Zandile

Authors: Kibane, Lebogang Zandile
Date: 2022-10-14
Subjects: Posthuman , Posthumanism , Anthropology , m-health , Wireless communication systems in medical care , Cyber-ethnography , Distress (Psychology)
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/408625 , vital:70510
Description: This dissertation explores the ways in which individuals embody cyborg realities through engaging with technological aids. It examines how these interactions have the potential to bring to light new ways of thinking about and experiencing daily distresses. Pertinent human technology interaction was observed through an overarching cyborg lens, embedded in posthumanist thought. The study began with a “human as cyborg” ontology that sought to impress upon readers the intimacy with which technology is entangled in our lives. It aimed to call to attention the use of the cyborg myth as it is concerned with “transgressed boundaries, potent fusions, and dangerous possibilities” (Haraway, 1985:7). The study followed a cyber ethnographic strategy, where cyber ethnography refers to a virtual research method that observes social and cultural phenomena that are mediated by online interactions. Data was collected over a period of eight months, beginning in December 2020 and ending in July 2021. It was collected through the following means: a short self-administered online questionnaire, computer mediated in-depth interviews, and group interviews. I also kept a journal on reflections of my own use of these supportive technologies. After analysing the results of in-depth interviews with nine primary participants and twenty-six online questionnaires, the following key themes were brought to light: Firstly, the tethered self, or cyborg self, engages in evolved acts of ‘care of the self’ mitigated through supportive technology use. Secondly, access to new technologies brings about new ways of performing the self. Thirdly, engagement with supportive technologies provides opportunity for aiding distress in the way of encouraging self-reflective and self-interrogation behaviours as seen in mobile health app use. This constant self-interrogation behaviour in turn develops a kind of technological dependency, characterized by escapism and evolved methods of self- soothing. Lastly, exploring the use of technology to aid distress revealed that technologies generate equal opportunities for improved well-being, as they do for a decreased sense of connectedness and security. The research demonstrates that supportive technology use is entangled in the fabric of our everyday lives. Through it we fashion our identities, alleviate distress, evade distress, and discover new causes of distress. , Thesis (MSocSci) -- Faculty of Humanities, Anthropology, 2022
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Date Issued: 2022-10-14

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Demand-side factors and the employment of young people: A case study of the recruitment and selection strategies of selected firms in Johannesburg

- Gabobegwe, Maoshadi Keletso Amanda

Authors: Gabobegwe, Maoshadi Keletso Amanda
Date: 2022-10-14
Subjects: Unemployment South Africa , Underemployment South Africa , Unemployed youth South Africa , Labor market South Africa , Employees Recruiting South Africa , Employer attitude surveys South Africa , International Labour Organisation
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/327294 , vital:61101 , DOI 10.21504/10962/327294
Description: Unemployment is a long-standing and pressing socio-economic phenomenon that affects, markedly, both developed and developing countries. Although, in one way or another, many people are affected by unemployment, the reviewed literature concurs that youth unemployment is a critical component of the overall unemployment challenge. Indeed, the burden of unemployment is borne, tremendously, by young people, especially those who are Not in Education, Employment, or Training (NEETs). The International Labour Organisation (ILO) has declared youth unemployment a global crisis, with approximately 67,6 million unemployed young people worldwide in 2018. In South Africa, the youth unemployment rate escalated to 56.4 per cent in the second quarter of 2019. This disturbing level of unemployment among young people poses a serious threat—for as long as young people stay unemployed. Indeed, the cost of unemployment is too high, not only does it engender discontent among young people who are floundering in poverty and frustration, but it can also trigger or perpetuate all sorts of social, political, and economic effects. These effects only exacerbate the already intricate and onerous global agenda of tackling unemployment— because they give rise to other socio-economic ills (e.g., crime, among others) that also need to be addressed. Owing to this grave and perpetual challenge of unemployment, exploring and understanding the dynamics of youth unemployment continues to be of paramount importance worldwide. This thesis, in particular, seeks to investigate the factors that impede on the employment of the NEETs category, as it may be extremely difficult for them to enter the labour market— and they may lose hope of entering the labour market later in life, if they are unsuccessful while still young. Unlike graduates or other youth categories (i.e., matriculants) who have better chances in the labour market, some young people (by virtue of being ‘dropouts’, teenage moms/dads, having failed matric, among other reasons), remain the most vulnerable to unemployment. For this reason, the primary aim of this thesis is to examine the ways in which employers’ recruitment strategies advantage or disadvantage young people (NEETs). The secondary aims include: (a) examining how employers' perceptions and attitudes, regarding the NEETs youths, influence their recruitment decisions when it comes to employing young people; and (b) understanding the ways in which government strategies (devised to combat youth unemployment) influence employers’ decisions to recruit the youths’ or not. In essence, this study seeks to explore the demand-side factors in the labour market that can help us understand how employers’ recruitment decisions (or recruitment behaviour) affect the employment prospects of young people in the labour market. The focus on demand-side factors is motivated by Labour Market Segmentation (LMS) theories, which serve as the theoretical framework of this thesis. LMS theories’ significance lies in their opposition to neoclassical economics, that posit the existence of a unified labour market (which operates like all other markets), consisting of buyers and sellers in ‘free’ competition. According to neoclassical theory, the difference between workers’ employment and wages is determined by ‘individual preferences’ and investments in ‘human capital’ (skills, experience, formal education, etc.). By contrast, LMS theorists argue that labour markets are fragmented, and that differences on the demand side imply differences in compensations that are not totally determined by individual workers' human capital. Inspired by the claims of LMS theories, this study elected to explore demand-side factors by applying qualitative research methods and techniques to gather and analyse the data gathered, and to ultimately address the research objectives. In particular, non-probability sampling was used to sample 20 firms from four sectors (manufacturing, retail/hospitality, finance, transportation) in the Johannesburg (CBD) region. The respondents were all asked a series of semi-structured questions in order to yield qualitative results that would help determine the employers’ dispositions towards young people; and about the government’s strategies that address youth unemployment. The aim is to provide an in-depth, nuanced understanding of how the respondents’ dispositions influence the inclusion or exclusion of young people in the employers’ recruitment considerations. The aggregate results of the study generally indicate that—although there are innumerable factors that affect young peoples' employment prospects—young people (without skills and tertiary education or matric) are actually being employed, and are still being considered for employment by the majority of the sampled employers (predominantly from retail/hospitality firms). Only a minority of employers stated, categorically, that they do not employ young people, and do not intend to do so. Conversely, the results also reveal that the the majority of employers often recruit young people for general and entry-level jobs that are often offered on a non-standard employment basis. At face value, the employment of young people (without skills) in the majority of the sampled firms may seem to make a difference—and it probably does, for as long as young people are exposed to the world of work. However, in the 4 grand scheme of things, the kind of employment offered in these firms is also problematic, because it is, basically, transient and unsustainable. As such, the young people that occupy these jobs are most likely to find themselves back in the unemployment queues whenever the ‘part-time’ or ‘temporary’ employment contracts are terminated. These jobs are especially problematic because policies such as the National Development Plan (NDP) 2030—in line with Sustainable Development Goals—aim to reduce poverty by creating sustainable employment. Contrarily, these kinds of jobs make it hard to achieve poverty reduction, because they are inherently unsustainable and barely lift people (especially young people) from unemployment and poverty. Based on these results, it can be asserted that the proliferation of non-standard employment compromises the agenda for decent work, and it delays the already sluggish Sustainable Development goal of creating sustainable employment (among other goals). This, then, reveals that there is still a stark and long-standing need for more radical strategies that will ensure the creation of sustainable jobs—without which the unemployment crisis will be far from over. Moreover, the results further indicate that the reasons why the minority of the sampled employers do not employ young people boil down to the fact that young people usually do not have what employers look for in their potential recruits; or that young people do not have what employers believe will contribute to the growth and productivity of their firms. In essence, employers will never employ any young person (or any jobseeker in general) that will be a liability than an asset in their firms. Over and above, this thesis corroborates many of the explanations—encapsulated in the growing literature—for rising unemployment, as well as the claims that unemployment is highly pronounced among young people. However, the contribution of this thesis is that it further offers a nuanced view to understanding the demand-side factors (as additional determinants) that hinder the employment of young people (especially those who make up the NEETs category). , Thesis (PhD) -- Faculty of Humanities, Sociology, 2022
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Date Issued: 2022-10-14

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Design, synthesis, manufacture, characterization and evaluation of lipid nanocapsules in chitosan-iota-carrageenan based hydrogel scaffold as a potential anti-Covid-19 drug delivery system

- Mukubwa, Grady Kathondo

Authors: Mukubwa, Grady Kathondo
Date: 2022-10-14
Subjects: Nanocapsules Design , Hydrogel , COVID-19 (Disease) , Characterization , Drug delivery systems
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/364955 , vital:65665
Description: Covid-19 is a deadly viral disease that has been rampant around the world since 2019. Although the successful introduction of the vaccine has reduced the spread of covid-19, new cases and deaths are still being recorded. To date, no specific curative antiviral treatment has been approved for covid-19. However, many existing antiviral drugs have been and are still being studied against covid-19 and some of them, such as Remdesivir, have shown promise and could be repurposed to treat this infection. Unfortunately, antiviral drugs are prone to resistance as most of them have poor biopharmaceutical properties, including low solubility, permeability and bioavailability, which could hinder any clinical success. Recent advances in nanotechnology-based delivery systems have made it possible to improve the biopharmaceutical properties of many drugs, especially those of poorly water-soluble drugs, by formulating them as lipid nanoparticles (LNP). Thus, in order to contribute to the fight against covid-19, this work aimed to develop Lipid Nanocapsules (LNC), based on some natural raw materials, which could improve the biopharmaceutical properties of antiviral drugs. In addition, since covid-19 infection is mainly respiratory, this work also aimed to fabricate a targeted delivery system based on a hydrogel capable of entrapping LNC and ensuring their efficient deposition and release in the lungs. The LNC consisted of a mixture of medium-chain triglycerides oil (MCT oil), crude soy lecithin, tween 80, NaCl and water, while the hydrogel consisted of a chitosan-grafted-iota carrageenan-grafted-poly (acrylamide-co-acrylic acid) system (CS-iCar-p (AAm-Co-AA)). Efavirenz (EFV), a drug with very low water solubility that has recently been demonstrated to have the potential to influence sars-cov-2 life cycle through different targets (3CLP, RdRp, Hellicase, 3’to5’exonuclease, 2’-O-ribose methyltransferase and EndoRNAse), was chosen as the model drug to evaluate the developed delivery system. The combination of LNP and hydrogel results in a delivery system known as the LNP-hydrogel composite, an emerging area of research in the field of drug delivery. To date, no research has reported the design and fabrication of an LNC-CS-iCar-p (AAm-Co-AA) hydrogel composite that could effectively deliver an antiviral drug to the lungs in addition to its advantages in terms of biological activities. Prior to the design of experiment, EFV solubility was assessed in water, labrafac lipophile 1349 and MCT oil. After that, the Design Expert Software version 13 was used to design the different experiments performed in this work. The I-optimal mixture design of experiments was performed for both LNC preparation and CS-iCar-p (AAm-Co-AA) hydrogel synthesis to study the impact of raw materials on the characteristics of these delivery systems. LNC were prepared using the phase inversion method while the free radical precipitation graft copolymerization method was used to synthesize hydrogel. In order to build polynomial models that could predict the amount of drug both LNC and CS-iCar-p (AAm-Co-AA) hydrogel can entrap, a D-optimal (custom) randomized design was performed. Moreover, various characterization techniques were used to investigate the physicochemical properties of the developed delivery systems. Thereafter, drug release studies were performed using a 1% sodium lauryl sulfate solution adjusted to either pH 4 or 7. Solubility studies revealed that EFV was more soluble in labrafac lipophile 1349 and in MCT oil than in water; therefore, given its affordability, MCT oil was used for the LNC formulation. The design of experiment carried out allowed the construction of polynomial models that could predict, on the one hand, the droplet size, the polydispersity index and the Zeta potential of LNC, which were respectively around 50nm, below 0.2 and below -33. On the other hand, the model could predict the swelling capacity of the synthesized hydrogel, which was optimised to about 30,000% (300 g of water to 1 g of hydrogel). This turned out to be influenced by the proportion of polymers, the ratio of monomers as well as the concentration of the cross-linking agent. In addition, the characterization techniques further supported the improvement of EFV solubility by highlighting its conversion into its amorphous state after encapsulation in LNC. They also confirmed successful synthesis of CS-iCar-p (AAm-co-AA) hydrogel. LNC were able to encapsulate about 87% of EFV while the synthesized CS-iCar-p (AAm-co-AA) hydrogel entrapped around 53% of EFV encapsulated in LNC. While LNC were able to release 42% and 27% of EFV after 74 hours in a 1% sodium lauryl sulfate solution (SLS) at pH 7 and pH 4 respectively, the LNC-CS-iCar-p (AAm-co-AA) hydrogel composite released about 50% and 40% of the drug after 9 days in the same release medium. Interestingly, the chemical integrity of the drug was preserved throughout the manufacturing process up to after its release, suggesting that the developed LNC-CS-iCar-p (AAm-co-AA) hydrogel composite could be used as a novel potential anticovid-19 drugs delivery system. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
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Date Issued: 2022-10-14

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