Formulation and evaluation of liposomal films for buccal delivery of antiretroviral drug
- Authors: Okafor, Nnamdi Ikemefuna
- Date: 2020
- Subjects: Liposomes , Highly active antiretroviral therapy , Antiretroviral agents , HIV infections -- Prevention
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/117161 , vital:34485
- Description: The human immune deficiency virus (HIV) infection has been ranked as one of the most devastating microbial infections in the world. This status is a result of the HIV rapid genetic variation, which limits discovery of a vaccine. Use application of antiretroviral therapy (ARVT) in treatment of the disease caused by the HIV infection (known as acquired immunodeficiency syndrome, HIV-AIDS) is frequently compromised by several factors such as the low bioavailability and severe adverse effects associated with the existing antiretroviral drugs (ARVDs). This underlines the need for controlling the pharmacokinetics profiles of ARVD using effective vehicles that can modify drug biodistribution. The same is true for many other conditions, where delivery systems can determine the success or failure of treatment by controlling pharmacokinetic and dynamic properties. The mucosal linings of the oral cavities in addition offer adorable route of administration for systematic drug delivery, improving drug therapeutic performance and often preferred by clinicians and patients. Liposomes are tiny spherical sacs of phospholipid molecules enclosing water droplets, formed (artificially) to carry drugs or other substances into the tissues by crossing and targeting to specific organelles. This work therefore focused on preparation of liposomes and liposomal buccal films (BFs) for potential buccal delivery of efavirenz, an ARVD model endowed with poor solubility and several side effects. The liposomes were prepared by thin film hydration method using crude soybean lecithin (CL) and cholesterol. Efavirenz loaded liposomes were evaluated for particle size, Zeta potential (ZP), morphology, encapsulation efficiency (EE%) and release kinetics studies. The physiochemical properties of the liposomes were also evaluated using Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), energy dispersity spectroscopy (EDS), and Fourier transform infrared (FTIR), while the formulation with the best encapsulation efficiency was used as the solvent medium for the buccal film formation. The buccal films were prepared using solvent casting method, where the liposomal suspension was used as the dispersing medium. The films were optimized for physical properties (thickness, weight variation and folding endurance) using digital Vernier calliper and digital weighing balance. The physiochemical properties of the selected BFs films made of Carbopol (CP) and its combination with Pluronic F127 (PF127) were further characterized using XRD, DSC, FTIR, Transmission Electron Microscopy (TEM), EDS and Scanning Electron Microscopy (SEM). The permeation study of the selected BFs was investigated using Franz diffusion cell. The BFs composed of CP alone or its combination with PF127 demonstrated much better bio-adhesive properties than the films made of other polymers (like Hydroxyl propyl methyl cellulose, HPMC) alone or in combination with PF127. The developed liposome formulation showed high encapsulation 98.8 ± 0.01 % in CL to cholesterol mass ratio of 1:1 and total lipid to drug mass ratio of 2:1. The average particle size 104.82 ± 2.29 nm and Zeta potential -50.33 ± 0.95 mV of these liposomes were found to be attractive for targeted delivery to the HIV infected cells. The CP based BFs (without and with PF127) exhibited good film thickness 0.88 ± 0.10 and 0.76 ± 0.14 mm, with weight uniformity 68.22 ± 1.04 and 86.28 ± 2. 16 mg, satisfactory flexibility values 258 and 321, and slightly acidic pH 6.43 ± 0.76 and 6.32 ± 0.01. The swelling percentage was found to be 50 % for CP film alone and 78 % for CP film with PF127. The cumulative amount of drug that permeated through the buccal epithelium over 24 hours was about 66 % from CP film alone and 75 % from CP film with PF127. Since no evidence of the liposomal encapsulation of EFV have been reported to our knowledge, we find the insights from the present study valuable as a set of preliminary data to encourage further investigations of the encapsulation and delivery of EFV like antiretrovirals for enhanced solubility, site targeting and prolonged release using crude soybean lecithin and mucoadhesive polymers, which holds some added economical values as naturally occurring lipid and polymeric mixtures as a promising delivery systems for buccal delivery of ARVDs.
- Full Text:
- Date Issued: 2020
- Authors: Okafor, Nnamdi Ikemefuna
- Date: 2020
- Subjects: Liposomes , Highly active antiretroviral therapy , Antiretroviral agents , HIV infections -- Prevention
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/117161 , vital:34485
- Description: The human immune deficiency virus (HIV) infection has been ranked as one of the most devastating microbial infections in the world. This status is a result of the HIV rapid genetic variation, which limits discovery of a vaccine. Use application of antiretroviral therapy (ARVT) in treatment of the disease caused by the HIV infection (known as acquired immunodeficiency syndrome, HIV-AIDS) is frequently compromised by several factors such as the low bioavailability and severe adverse effects associated with the existing antiretroviral drugs (ARVDs). This underlines the need for controlling the pharmacokinetics profiles of ARVD using effective vehicles that can modify drug biodistribution. The same is true for many other conditions, where delivery systems can determine the success or failure of treatment by controlling pharmacokinetic and dynamic properties. The mucosal linings of the oral cavities in addition offer adorable route of administration for systematic drug delivery, improving drug therapeutic performance and often preferred by clinicians and patients. Liposomes are tiny spherical sacs of phospholipid molecules enclosing water droplets, formed (artificially) to carry drugs or other substances into the tissues by crossing and targeting to specific organelles. This work therefore focused on preparation of liposomes and liposomal buccal films (BFs) for potential buccal delivery of efavirenz, an ARVD model endowed with poor solubility and several side effects. The liposomes were prepared by thin film hydration method using crude soybean lecithin (CL) and cholesterol. Efavirenz loaded liposomes were evaluated for particle size, Zeta potential (ZP), morphology, encapsulation efficiency (EE%) and release kinetics studies. The physiochemical properties of the liposomes were also evaluated using Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), energy dispersity spectroscopy (EDS), and Fourier transform infrared (FTIR), while the formulation with the best encapsulation efficiency was used as the solvent medium for the buccal film formation. The buccal films were prepared using solvent casting method, where the liposomal suspension was used as the dispersing medium. The films were optimized for physical properties (thickness, weight variation and folding endurance) using digital Vernier calliper and digital weighing balance. The physiochemical properties of the selected BFs films made of Carbopol (CP) and its combination with Pluronic F127 (PF127) were further characterized using XRD, DSC, FTIR, Transmission Electron Microscopy (TEM), EDS and Scanning Electron Microscopy (SEM). The permeation study of the selected BFs was investigated using Franz diffusion cell. The BFs composed of CP alone or its combination with PF127 demonstrated much better bio-adhesive properties than the films made of other polymers (like Hydroxyl propyl methyl cellulose, HPMC) alone or in combination with PF127. The developed liposome formulation showed high encapsulation 98.8 ± 0.01 % in CL to cholesterol mass ratio of 1:1 and total lipid to drug mass ratio of 2:1. The average particle size 104.82 ± 2.29 nm and Zeta potential -50.33 ± 0.95 mV of these liposomes were found to be attractive for targeted delivery to the HIV infected cells. The CP based BFs (without and with PF127) exhibited good film thickness 0.88 ± 0.10 and 0.76 ± 0.14 mm, with weight uniformity 68.22 ± 1.04 and 86.28 ± 2. 16 mg, satisfactory flexibility values 258 and 321, and slightly acidic pH 6.43 ± 0.76 and 6.32 ± 0.01. The swelling percentage was found to be 50 % for CP film alone and 78 % for CP film with PF127. The cumulative amount of drug that permeated through the buccal epithelium over 24 hours was about 66 % from CP film alone and 75 % from CP film with PF127. Since no evidence of the liposomal encapsulation of EFV have been reported to our knowledge, we find the insights from the present study valuable as a set of preliminary data to encourage further investigations of the encapsulation and delivery of EFV like antiretrovirals for enhanced solubility, site targeting and prolonged release using crude soybean lecithin and mucoadhesive polymers, which holds some added economical values as naturally occurring lipid and polymeric mixtures as a promising delivery systems for buccal delivery of ARVDs.
- Full Text:
- Date Issued: 2020
Factors contributing to paediatric HIV diclosure by caregivers
- Authors: Van der Meulen, Christine
- Date: 2016X
- Subjects: HIV-positive children -- Care -- South Africa. Caregivers -- South Africa -- Eastern Cape. , Highly active antiretroviral therapy
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10948/13359 , vital:27178
- Description: Due to the increasing availability of ART (antiretroviral therapy),HIV is starting to be seen as a chronic disease. This has several effects on families, one of which is the need to disclose their HIV status to children who were born with the illness. Potential barriers and available support structures with regards to paediatric HIV disclosure need to be considered before specific guidelines can be given to caretakers and health care providers. This study aimed to explore and describe the patterns of paediatric HIV disclosure or non-disclosure using a sample of caretakers or parents of children/adolescents who were born with HIV. The Disclosure Decision Making Model (DDMM) was used as a framework to understand the decision-making process that leads to either disclosure or non-disclosure. Qualitative data was gathered by means of in-depth, semi-structured interviews, conducted in English. Ten participants were recruited from a community health care centre that offers HIV counselling and testing in the Nelson Mandela Bay Health District. Data gathered was transcribed and analysed using thematic analysis. Lincoln and Guba’s model was used to determine the trustworthiness of the data. The two themes that emerged from the study were (1) caretakers wish to disclose HIV status to the child but identified barriers to doing this and, (2) caretakers identified factors that helped them to disclose the child’s status. This study provides a more in-depth understanding of the factors that influence disclosure in a resource-limited setting in the Eastern Cape.
- Full Text:
- Date Issued: 2016X
- Authors: Van der Meulen, Christine
- Date: 2016X
- Subjects: HIV-positive children -- Care -- South Africa. Caregivers -- South Africa -- Eastern Cape. , Highly active antiretroviral therapy
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10948/13359 , vital:27178
- Description: Due to the increasing availability of ART (antiretroviral therapy),HIV is starting to be seen as a chronic disease. This has several effects on families, one of which is the need to disclose their HIV status to children who were born with the illness. Potential barriers and available support structures with regards to paediatric HIV disclosure need to be considered before specific guidelines can be given to caretakers and health care providers. This study aimed to explore and describe the patterns of paediatric HIV disclosure or non-disclosure using a sample of caretakers or parents of children/adolescents who were born with HIV. The Disclosure Decision Making Model (DDMM) was used as a framework to understand the decision-making process that leads to either disclosure or non-disclosure. Qualitative data was gathered by means of in-depth, semi-structured interviews, conducted in English. Ten participants were recruited from a community health care centre that offers HIV counselling and testing in the Nelson Mandela Bay Health District. Data gathered was transcribed and analysed using thematic analysis. Lincoln and Guba’s model was used to determine the trustworthiness of the data. The two themes that emerged from the study were (1) caretakers wish to disclose HIV status to the child but identified barriers to doing this and, (2) caretakers identified factors that helped them to disclose the child’s status. This study provides a more in-depth understanding of the factors that influence disclosure in a resource-limited setting in the Eastern Cape.
- Full Text:
- Date Issued: 2016X
Factors contributing to paediatric HIV diclosure by caregivers
- Authors: Van der Meulen, Christine
- Date: 2016
- Subjects: HIV-positive children -- Care -- South Africa Caregivers -- South Africa -- Eastern Cape , Highly active antiretroviral therapy
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10948/45514 , vital:38623
- Description: Due to the increasing availability of ART (antiretroviral therapy), HIV is starting to be seen as a chronic disease. This has several effects on families, one of which is the need to disclose their HIV status to children who were born with the illness. Potential barriers and available support structures with regards to paediatric HIV disclosure need to be considered before specific guidelines can be given to caretakers and health care providers. This study aimed to explore and describe the patterns of paediatric HIV disclosure or non-disclosure using a sample of caretakers or parents of Children/adolescents who were born with HIV. The Disclosure Decision Making Model (DDMM) was used as a framework to understand the decision-making process that leads to either disclosure or non-disclosure. Qualitative data was gathered by means of in-depth, semi-structured interviews, conducted in English. Ten participants were recruited from a community health care centre that offers HIV counselling and testing in the Nelson Mandela Bay Health District. Data gathered was transcribed and analysed using thematic analysis. Lincoln and Guba’s model were used to determine the trustworthiness of the data. The two themes that emerged from the study were (1) caretakers wish to disclose HIV status to the child but identified barriers to doing this and, (2) caretakers identified factors that helped them to disclose the child’s status. This study provides a more in-depth understanding of the factors that influence disclosure in a resource-limited setting in the Eastern Cape.
- Full Text:
- Date Issued: 2016
- Authors: Van der Meulen, Christine
- Date: 2016
- Subjects: HIV-positive children -- Care -- South Africa Caregivers -- South Africa -- Eastern Cape , Highly active antiretroviral therapy
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10948/45514 , vital:38623
- Description: Due to the increasing availability of ART (antiretroviral therapy), HIV is starting to be seen as a chronic disease. This has several effects on families, one of which is the need to disclose their HIV status to children who were born with the illness. Potential barriers and available support structures with regards to paediatric HIV disclosure need to be considered before specific guidelines can be given to caretakers and health care providers. This study aimed to explore and describe the patterns of paediatric HIV disclosure or non-disclosure using a sample of caretakers or parents of Children/adolescents who were born with HIV. The Disclosure Decision Making Model (DDMM) was used as a framework to understand the decision-making process that leads to either disclosure or non-disclosure. Qualitative data was gathered by means of in-depth, semi-structured interviews, conducted in English. Ten participants were recruited from a community health care centre that offers HIV counselling and testing in the Nelson Mandela Bay Health District. Data gathered was transcribed and analysed using thematic analysis. Lincoln and Guba’s model were used to determine the trustworthiness of the data. The two themes that emerged from the study were (1) caretakers wish to disclose HIV status to the child but identified barriers to doing this and, (2) caretakers identified factors that helped them to disclose the child’s status. This study provides a more in-depth understanding of the factors that influence disclosure in a resource-limited setting in the Eastern Cape.
- Full Text:
- Date Issued: 2016
Identifying, recording and monitoring adverse effects associated with antriretroviral treatment
- Authors: Mulinge, Florence Muthoni
- Date: 2010
- Subjects: Highly active antiretroviral therapy , Antiretroviral agents -- South Africa -- Uitenhage , HIV infections -- Treatment -- South Africa -- Uitenhage , AIDS (Disease) -- Treatment -- South Africa -- Uitenhage
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:10131 , http://hdl.handle.net/10948/1491 , Highly active antiretroviral therapy , Antiretroviral agents -- South Africa -- Uitenhage , HIV infections -- Treatment -- South Africa -- Uitenhage , AIDS (Disease) -- Treatment -- South Africa -- Uitenhage
- Description: South Africa, with an estimated 5.7 million people living with HIV, continues to have one of the largest epidemics in the world. The introduction of HAART resulted in prolonged and improved quality of life of many infected patients. However, adverse effects caused by these drugs have become a major concern as they affect the adherence of patients and in some cases even result in the death of patients. Although much research has been and is still being conducted in the area of understanding, preventing and management of ARV adverse effects, there is still a need for patients to be actively involved in self-monitoring for adverse effects. This will assist health care professionals in early identification of serious or potentially serious ARV effects. This study aimed at evaluating the usefulness of strategies developed and employed in the identification, recording and monitoring of adverse effects. The study was conducted with patients receiving HAART from a private HIV and AIDS clinic in Uitenhage, Eastern Cape, South Africa. The research project was approved by the Nelson Mandela Metropolitan University Research and Ethics Committee and the research site. This was an experimental, randomized controlled study carried out over a period of three months (August to October 2009), with a sample size of 160 patients divided into four study groups of 40 patients each. Two monitoring strategies, namely an ARV adverse effect monitoring tool and a patient self-monitoring diary were developed and used for the identification and recording of adverse effects. The four study groups included a Control group, a Tool group, a Diary group and a Tool-Diary group. Willing patients, after signing an informed consent form, were randomly assigned to one of the four groups by participating health care workers at the study site. Data was retrieved from the patient files by the researcher. Descriptive statistical analysis of the findings of the study was conducted using SPSS®. One hundred and forty nine patients were included in the final data analysis. Of the 80 diaries handed out to patients, only 33 were returned and due to errors only 31 were suitable for analysis. Monitoring tools were completed and analysed for 36 patients. The tool was found to be more effective in identifying adverse effects of a physical nature (such as peripheral neuropathy and lipodystrophy) than the usual methods of monitoring employed by the clinic, whilst the diary, used alone, was found to be less effective. Use of the tool and diary combined resulted in the most significant identification and recording of central nervous system related adverse effects and physical adverse effects. However due to the low return rate of the diaries and the majority of the monitoring tool not being completed in many instances the results of this study may not be generalisable. The study results did however suggest that combining the tool and the diary methods of adverse effect identification, yielded the most favourable results when compared to each method alone. This may be attributed to the fact that the tool is useful in identifying objective symptoms and the diaries subjective symptoms, particularly in instances where the patients forget to report their symptoms to healthcare professional whilst at the clinic. The diaries were also reported to improve adherence for more than 90 percentage (n=31) of the patients. More research would be needed in order to verify the exact significance of the tool and the diary in identifying and recording adverse effects and symptoms of adverse effects.
- Full Text:
- Date Issued: 2010
- Authors: Mulinge, Florence Muthoni
- Date: 2010
- Subjects: Highly active antiretroviral therapy , Antiretroviral agents -- South Africa -- Uitenhage , HIV infections -- Treatment -- South Africa -- Uitenhage , AIDS (Disease) -- Treatment -- South Africa -- Uitenhage
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:10131 , http://hdl.handle.net/10948/1491 , Highly active antiretroviral therapy , Antiretroviral agents -- South Africa -- Uitenhage , HIV infections -- Treatment -- South Africa -- Uitenhage , AIDS (Disease) -- Treatment -- South Africa -- Uitenhage
- Description: South Africa, with an estimated 5.7 million people living with HIV, continues to have one of the largest epidemics in the world. The introduction of HAART resulted in prolonged and improved quality of life of many infected patients. However, adverse effects caused by these drugs have become a major concern as they affect the adherence of patients and in some cases even result in the death of patients. Although much research has been and is still being conducted in the area of understanding, preventing and management of ARV adverse effects, there is still a need for patients to be actively involved in self-monitoring for adverse effects. This will assist health care professionals in early identification of serious or potentially serious ARV effects. This study aimed at evaluating the usefulness of strategies developed and employed in the identification, recording and monitoring of adverse effects. The study was conducted with patients receiving HAART from a private HIV and AIDS clinic in Uitenhage, Eastern Cape, South Africa. The research project was approved by the Nelson Mandela Metropolitan University Research and Ethics Committee and the research site. This was an experimental, randomized controlled study carried out over a period of three months (August to October 2009), with a sample size of 160 patients divided into four study groups of 40 patients each. Two monitoring strategies, namely an ARV adverse effect monitoring tool and a patient self-monitoring diary were developed and used for the identification and recording of adverse effects. The four study groups included a Control group, a Tool group, a Diary group and a Tool-Diary group. Willing patients, after signing an informed consent form, were randomly assigned to one of the four groups by participating health care workers at the study site. Data was retrieved from the patient files by the researcher. Descriptive statistical analysis of the findings of the study was conducted using SPSS®. One hundred and forty nine patients were included in the final data analysis. Of the 80 diaries handed out to patients, only 33 were returned and due to errors only 31 were suitable for analysis. Monitoring tools were completed and analysed for 36 patients. The tool was found to be more effective in identifying adverse effects of a physical nature (such as peripheral neuropathy and lipodystrophy) than the usual methods of monitoring employed by the clinic, whilst the diary, used alone, was found to be less effective. Use of the tool and diary combined resulted in the most significant identification and recording of central nervous system related adverse effects and physical adverse effects. However due to the low return rate of the diaries and the majority of the monitoring tool not being completed in many instances the results of this study may not be generalisable. The study results did however suggest that combining the tool and the diary methods of adverse effect identification, yielded the most favourable results when compared to each method alone. This may be attributed to the fact that the tool is useful in identifying objective symptoms and the diaries subjective symptoms, particularly in instances where the patients forget to report their symptoms to healthcare professional whilst at the clinic. The diaries were also reported to improve adherence for more than 90 percentage (n=31) of the patients. More research would be needed in order to verify the exact significance of the tool and the diary in identifying and recording adverse effects and symptoms of adverse effects.
- Full Text:
- Date Issued: 2010
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