Echogenic liposomes for ultrasound-triggered drug delivery
- Authors: Izuchukwu, Ezekiel Charles
- Date: 2021-10
- Subjects: Liposomes , Drug delivery systems , Colon (Anatomy) Cancer Treatment , Transmission electron microscopy , Fourier transform infrared spectroscopy , Liquid chromatography , Echogenic liposomes , Ultrasound-triggered drug delivery
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188997 , vital:44805
- Description: Colorectal cancer is one of common cancers worldwide. It is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) alone or in a chemotherapy regime has been the effective treatment of colorectal cancer patients. The efficacy of 5-FU in colorectal cancer treatment is significantly limited by drug resistance, gastrointestinal, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying a need to improve its therapeutic index. Liposomes are colloidal membranes comprising of one or more lipid bilayers enclosing an aqueous core. They have been used to improve the therapeutic index of many anti-cancer drugs by changing drug absorption, elongating biological half-life, reducing metabolism, and reducing toxicity to healthy tissues. Echogenic liposomes are specifically designed to respond to external triggering like ultrasound stimulation by entrapping a gas or an emulsion that can vaporize. A liposome's unique property is that it can entrap both hydrophobic and hydrophilic substances simultaneously in the lipid bilayer and the aqueous core, respectively. These stimuli-responsive liposomes can be triggered externally with ultrasound, to release the chemotherapeutic cargo only at the required site. This research aims to formulate echogenic liposomes encapsulating 5-FU for potential ultrasound triggered release (echogenic). Liposome formulations wereprepared with lipid composition of crude soybean lecithin and cholesterol by thin-filmhydration method and the drug was passively loaded in the formulation. The 5-FU loadedliposomes were evaluated by dynamic light scattering (DLS) for particle size, polydispersityindex, and zeta potential and transmission electron microscopy (TEM) for morphology.Encapsulated liposomal formulations were also evaluated using physicochemical techniquesincluding thermogravimetric analysis (TGA), differential scanning calorimetry (DSC),Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Theencapsulation efficiency and release kinetics were studied using a validated high-performanceliquid chromatography (HPLC) method. Echogenic properties were explored by entrapping abiocompatible gas (argon) at the same time as the drug (5-FU) using a pressure/freezemethodology. The liposomal formulations were typically spherical with a size of about 150 nmand encapsulation efficiency of 62%. Low-frequency ultrasound (20 kHz) was used to triggerthe drug release from the complete formulation at 10%, 15%, and 20% amplitude and exposuretime of 5 min and 10 min. The rate of drug release from the nano-carrier was a function of theultrasound amplitude and exposure time and reached a maximum of 65% release under theconditions investigated. The cumulative release was investigated, with and without theapplication of ultrasound. It was demonstrated that the application of ultrasound resulted in complete release (99%) after 12 h while this dropped to 70% without ultrasound. These results are encouraging for optimizing ultrasound parameters for triggered and controlled release of the 5-FU, for conditions such as the management of cancer where low-power ultrasound can be applied. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Izuchukwu, Ezekiel Charles
- Date: 2021-10
- Subjects: Liposomes , Drug delivery systems , Colon (Anatomy) Cancer Treatment , Transmission electron microscopy , Fourier transform infrared spectroscopy , Liquid chromatography , Echogenic liposomes , Ultrasound-triggered drug delivery
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188997 , vital:44805
- Description: Colorectal cancer is one of common cancers worldwide. It is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) alone or in a chemotherapy regime has been the effective treatment of colorectal cancer patients. The efficacy of 5-FU in colorectal cancer treatment is significantly limited by drug resistance, gastrointestinal, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying a need to improve its therapeutic index. Liposomes are colloidal membranes comprising of one or more lipid bilayers enclosing an aqueous core. They have been used to improve the therapeutic index of many anti-cancer drugs by changing drug absorption, elongating biological half-life, reducing metabolism, and reducing toxicity to healthy tissues. Echogenic liposomes are specifically designed to respond to external triggering like ultrasound stimulation by entrapping a gas or an emulsion that can vaporize. A liposome's unique property is that it can entrap both hydrophobic and hydrophilic substances simultaneously in the lipid bilayer and the aqueous core, respectively. These stimuli-responsive liposomes can be triggered externally with ultrasound, to release the chemotherapeutic cargo only at the required site. This research aims to formulate echogenic liposomes encapsulating 5-FU for potential ultrasound triggered release (echogenic). Liposome formulations wereprepared with lipid composition of crude soybean lecithin and cholesterol by thin-filmhydration method and the drug was passively loaded in the formulation. The 5-FU loadedliposomes were evaluated by dynamic light scattering (DLS) for particle size, polydispersityindex, and zeta potential and transmission electron microscopy (TEM) for morphology.Encapsulated liposomal formulations were also evaluated using physicochemical techniquesincluding thermogravimetric analysis (TGA), differential scanning calorimetry (DSC),Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Theencapsulation efficiency and release kinetics were studied using a validated high-performanceliquid chromatography (HPLC) method. Echogenic properties were explored by entrapping abiocompatible gas (argon) at the same time as the drug (5-FU) using a pressure/freezemethodology. The liposomal formulations were typically spherical with a size of about 150 nmand encapsulation efficiency of 62%. Low-frequency ultrasound (20 kHz) was used to triggerthe drug release from the complete formulation at 10%, 15%, and 20% amplitude and exposuretime of 5 min and 10 min. The rate of drug release from the nano-carrier was a function of theultrasound amplitude and exposure time and reached a maximum of 65% release under theconditions investigated. The cumulative release was investigated, with and without theapplication of ultrasound. It was demonstrated that the application of ultrasound resulted in complete release (99%) after 12 h while this dropped to 70% without ultrasound. These results are encouraging for optimizing ultrasound parameters for triggered and controlled release of the 5-FU, for conditions such as the management of cancer where low-power ultrasound can be applied. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
Effects of elevated temperature, rainfall and soil nutrients on acacia mearnsii invasion
- Authors: Kharivha, Tshililo
- Date: 2021-10
- Subjects: Acacia mearnsii , Acacia mearnsii Effect of high temperatures on South Africa , Acacia mearnsii Climatic factors South Africa , Plant invasions South Africa , Invasive plants , Climatic changes South Africa
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/189997 , vital:44954
- Description: Climate change is associated with the risk of plant invasion hence a better understanding of the effects of elevated temperature, precipitation and soil nutrients on dominant invasive plants is needed for effective ecological planning. This study was set out to: (i) examine how elevated temperature (±2°C increase), (ii) high (above local average) and low (below local average) precipitation, (iii) elevated soil nutrient content (increase in soil N), and (iv) a combination of the above manipulations affects germination and growth of Acacia mearnsii, a dominant invasive plant in South Africa. The study further evaluated how the above-mentioned treatments affect soil chemical properties following A. mearnsii germination and growth. The above-mentioned specific objectives were tested under manipulated greenhouse conditions over six experimental months. The results indicated that the above-mentioned climate change scenarios have the potential to facilitate germination and growth of the invasive species A. mearnsii, and this is likely to proliferate its invasion in future. Results showed that seed germination was significantly high under all climate change manipulation treatments (˃50%) with highest seed germination recorded under high rainfall treatment (64%). Plant height was significantly higher under high temperature and high rainfall treatments throughout all the experimental months, though it was lowest under high nitrogen and combined treatment with high rainfall. The numbers of branches were high under higher temperature and low rainfall treatments than under high rainfall, high nitrogen and both combined treatments of low and high rainfall. Relative to the control, plants grown under climate change scenarios increased their root lengths, but this varied across different treatments. Total dry biomass was relatively high under high temperature treatment (0,7 g). Lower plant dry biomass was observed under low and high rainfall treatments (0,4 g), high nitrogen and combined treatments with both low and high rainfall treatments (0,1 g). Concerning the effects of climate change scenarios on soil chemical properties, soil pH levels were significantly higher after A. mearnsii germination and growth than before the experiment was setup. Soil resistivity was significantly higher in climate change treatments receiving nitrogen and combined treatments of low rainfall than other treatments and the soils before experiment. Soil total P was significantly higher in all the climate change treatments after A. mearnsii germination experiment than the before experiment soils. Soils receiving high temperature, high nitrogen, and combined treatment of low rainfall had significantly higher soil total N than other treatments and the before experiment soils. Soil total C was significantly higher in soils receiving high temperature, high nitrogen, and combined treatment of low rainfall after A. mearnsii germination than other treatments and before experiment soils. The findings suggest that future climate change scenarios of increased temperature and rainfall with soil nutrients could considerably enhance growth and germination success of the invasive plant A. mearnsii. Similarly, climate change scenarios could enhance some soil nutrient properties, which in turn, is likely to give the invasive plant A. mearnsii a germination and growth advantage. These results are the first in South Africa to show that future climate changes have the potential to facilitate A. mearnsii germination and growth, making it more invasive. The findings have implications for invasive plants management, especially action for managing the plant through clearing of the plant in sensitive ecosystems (e.g. riparian systems). , Thesis (MSc) -- Faculty of Science, Environmental Science, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Kharivha, Tshililo
- Date: 2021-10
- Subjects: Acacia mearnsii , Acacia mearnsii Effect of high temperatures on South Africa , Acacia mearnsii Climatic factors South Africa , Plant invasions South Africa , Invasive plants , Climatic changes South Africa
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/189997 , vital:44954
- Description: Climate change is associated with the risk of plant invasion hence a better understanding of the effects of elevated temperature, precipitation and soil nutrients on dominant invasive plants is needed for effective ecological planning. This study was set out to: (i) examine how elevated temperature (±2°C increase), (ii) high (above local average) and low (below local average) precipitation, (iii) elevated soil nutrient content (increase in soil N), and (iv) a combination of the above manipulations affects germination and growth of Acacia mearnsii, a dominant invasive plant in South Africa. The study further evaluated how the above-mentioned treatments affect soil chemical properties following A. mearnsii germination and growth. The above-mentioned specific objectives were tested under manipulated greenhouse conditions over six experimental months. The results indicated that the above-mentioned climate change scenarios have the potential to facilitate germination and growth of the invasive species A. mearnsii, and this is likely to proliferate its invasion in future. Results showed that seed germination was significantly high under all climate change manipulation treatments (˃50%) with highest seed germination recorded under high rainfall treatment (64%). Plant height was significantly higher under high temperature and high rainfall treatments throughout all the experimental months, though it was lowest under high nitrogen and combined treatment with high rainfall. The numbers of branches were high under higher temperature and low rainfall treatments than under high rainfall, high nitrogen and both combined treatments of low and high rainfall. Relative to the control, plants grown under climate change scenarios increased their root lengths, but this varied across different treatments. Total dry biomass was relatively high under high temperature treatment (0,7 g). Lower plant dry biomass was observed under low and high rainfall treatments (0,4 g), high nitrogen and combined treatments with both low and high rainfall treatments (0,1 g). Concerning the effects of climate change scenarios on soil chemical properties, soil pH levels were significantly higher after A. mearnsii germination and growth than before the experiment was setup. Soil resistivity was significantly higher in climate change treatments receiving nitrogen and combined treatments of low rainfall than other treatments and the soils before experiment. Soil total P was significantly higher in all the climate change treatments after A. mearnsii germination experiment than the before experiment soils. Soils receiving high temperature, high nitrogen, and combined treatment of low rainfall had significantly higher soil total N than other treatments and the before experiment soils. Soil total C was significantly higher in soils receiving high temperature, high nitrogen, and combined treatment of low rainfall after A. mearnsii germination than other treatments and before experiment soils. The findings suggest that future climate change scenarios of increased temperature and rainfall with soil nutrients could considerably enhance growth and germination success of the invasive plant A. mearnsii. Similarly, climate change scenarios could enhance some soil nutrient properties, which in turn, is likely to give the invasive plant A. mearnsii a germination and growth advantage. These results are the first in South Africa to show that future climate changes have the potential to facilitate A. mearnsii germination and growth, making it more invasive. The findings have implications for invasive plants management, especially action for managing the plant through clearing of the plant in sensitive ecosystems (e.g. riparian systems). , Thesis (MSc) -- Faculty of Science, Environmental Science, 2021
- Full Text:
- Date Issued: 2021-10
Is there an inverse-u relationship between financialisation and investment?: South Africa’s stock market capitalisation in comparative perspective
- Authors: Owen, Michael Robert
- Date: 2021-10
- Subjects: Monetary policy South Africa , Globalization , Economics South Africa , Capital movements South Africa , Stock exchanges South Africa , Investments South Africa , Economic development South Africa , South Africa Economic conditions 1991-
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/191084 , vital:45058
- Description: In recent decades, the growth and fluctuations in the financial sector have become increasingly disjointed from events in the real economy. There has been a dramatic increase in global market integration and globalisation since the 2008 financial crisis. The argument presented in the thesis shows perspective from the two general debates in Economics. The Orthodox view, which suggests there is an efficient flow of resources between people and institutions over time, supports the argument that there is a positive relationship between financialisation and economic growth. Alternatively, the Heterodox view argues that financial liberalisation fails to anticipate market effects and requires intervention in order to limit negative consequences. More recent studies have proposed an inverse-U theory between financialisation and investment, which suggests that there is a threshold, above which further financial development and financial globalisation has detrimental effects on the real economy. With South Africa being a developing country that is highly reliant on capital inflows to finance the economy, there is space for more acute research to investigate whether South Africa has surpassed this threshold. This study focusses on one aspect of this relationship, namely the relationship between Stock Market Capitalisation and Investment. It uses panel data analysis and other methods to explore whether such an inverse-U relationship exists internationally, and whether South Africa is suffering from the effects of financialisation. , Thesis (MCom) -- Faculty of Commerce, Economics and Economic History, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Owen, Michael Robert
- Date: 2021-10
- Subjects: Monetary policy South Africa , Globalization , Economics South Africa , Capital movements South Africa , Stock exchanges South Africa , Investments South Africa , Economic development South Africa , South Africa Economic conditions 1991-
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/191084 , vital:45058
- Description: In recent decades, the growth and fluctuations in the financial sector have become increasingly disjointed from events in the real economy. There has been a dramatic increase in global market integration and globalisation since the 2008 financial crisis. The argument presented in the thesis shows perspective from the two general debates in Economics. The Orthodox view, which suggests there is an efficient flow of resources between people and institutions over time, supports the argument that there is a positive relationship between financialisation and economic growth. Alternatively, the Heterodox view argues that financial liberalisation fails to anticipate market effects and requires intervention in order to limit negative consequences. More recent studies have proposed an inverse-U theory between financialisation and investment, which suggests that there is a threshold, above which further financial development and financial globalisation has detrimental effects on the real economy. With South Africa being a developing country that is highly reliant on capital inflows to finance the economy, there is space for more acute research to investigate whether South Africa has surpassed this threshold. This study focusses on one aspect of this relationship, namely the relationship between Stock Market Capitalisation and Investment. It uses panel data analysis and other methods to explore whether such an inverse-U relationship exists internationally, and whether South Africa is suffering from the effects of financialisation. , Thesis (MCom) -- Faculty of Commerce, Economics and Economic History, 2021
- Full Text:
- Date Issued: 2021-10
Scaffolding argumentative writing through Reading to Learn (RtL) pedagogy: a case study of three grade 11 English second language teachers in Namibia
- Authors: Matengu, Ernest Samubu
- Date: 2021-10
- Subjects: Rose, David, 1955- , Reading (Secondary) , Persuasion (Rhetoric) Study and teaching (Secondary) Namibia , English language Writing Study and teaching (Secondary) Namibia , English language Rhetoric Study and teaching (Secondary) Namibia , English language Study and teaching (Secondary) Foreign speakers Case studies , Reading to Learn , Scaffolding Interaction Cycle
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/191148 , vital:45065
- Description: The central aim of this study was to investigate the positive impact of Reading to Learn (RtL) pedagogy in enhancing Grade 11 learners’ argumentative writing skills. This was a case study of one school in Otjozondjupa region in Namibia. The pedagogy, RtL, was designed to address learning inequalities with marginalised communities in Australia. Coupled with challenges in literacy development in learners, current methods have not successfully addressed the teaching and learning of argumentative writing amidst learning inequalities. This study employed the six stages of Scaffolding Interaction Cycle of RtL in order to teach argumentative writing. As is evidenced in recent research, the scaffolding cycle of RtL provides equal opportunities to learners from diverse backgrounds to attain epistemological access at the same pace. RtL’s theoretical and conceptual framework is derived from Bernstein’s theory of education as pedagogic discourse (a device for maintaining inequality in society), Vygotsky’s theory of learning as a social process and Halliday’s model of language as text in social context. The two research questions for this study were: (1) What role does Reading to Learn (RtL) pedagogy play in developing Grade 11 learners’ ability to write argumentative essays? And (2) How can the implementation of RtL pedagogy through scaffolding impact on/improve learners’ literacy skills development for argumentative essay writing? This qualitative case study generated data through observation of three teachers’ lessons, a Stimulated Recall Interview (SRI) conducted with the three teachers and learners’ pre and posttest of argumentative essays. The findings of this study revealed that teachers found RtL as a comprehensive pedagogy that makes teaching and learning of argumentative writing successful through systematic scaffolding of learning. Learners’ written pre and posttest also showed a narrowing of the gap between weak and strong learners in that weak learners recorded an upward trend similar to that of strong learners in their posttest. Given the design of RtL and studies conducted globally, the findings of this study can be comparable. , Thesis (MEd) -- Faculty of Education, Education, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Matengu, Ernest Samubu
- Date: 2021-10
- Subjects: Rose, David, 1955- , Reading (Secondary) , Persuasion (Rhetoric) Study and teaching (Secondary) Namibia , English language Writing Study and teaching (Secondary) Namibia , English language Rhetoric Study and teaching (Secondary) Namibia , English language Study and teaching (Secondary) Foreign speakers Case studies , Reading to Learn , Scaffolding Interaction Cycle
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/191148 , vital:45065
- Description: The central aim of this study was to investigate the positive impact of Reading to Learn (RtL) pedagogy in enhancing Grade 11 learners’ argumentative writing skills. This was a case study of one school in Otjozondjupa region in Namibia. The pedagogy, RtL, was designed to address learning inequalities with marginalised communities in Australia. Coupled with challenges in literacy development in learners, current methods have not successfully addressed the teaching and learning of argumentative writing amidst learning inequalities. This study employed the six stages of Scaffolding Interaction Cycle of RtL in order to teach argumentative writing. As is evidenced in recent research, the scaffolding cycle of RtL provides equal opportunities to learners from diverse backgrounds to attain epistemological access at the same pace. RtL’s theoretical and conceptual framework is derived from Bernstein’s theory of education as pedagogic discourse (a device for maintaining inequality in society), Vygotsky’s theory of learning as a social process and Halliday’s model of language as text in social context. The two research questions for this study were: (1) What role does Reading to Learn (RtL) pedagogy play in developing Grade 11 learners’ ability to write argumentative essays? And (2) How can the implementation of RtL pedagogy through scaffolding impact on/improve learners’ literacy skills development for argumentative essay writing? This qualitative case study generated data through observation of three teachers’ lessons, a Stimulated Recall Interview (SRI) conducted with the three teachers and learners’ pre and posttest of argumentative essays. The findings of this study revealed that teachers found RtL as a comprehensive pedagogy that makes teaching and learning of argumentative writing successful through systematic scaffolding of learning. Learners’ written pre and posttest also showed a narrowing of the gap between weak and strong learners in that weak learners recorded an upward trend similar to that of strong learners in their posttest. Given the design of RtL and studies conducted globally, the findings of this study can be comparable. , Thesis (MEd) -- Faculty of Education, Education, 2021
- Full Text:
- Date Issued: 2021-10
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