Enhancement of Biological and Pharmacological Properties of an Encapsulated Polyphenol: Curcumin
- Witika, Bwalya A, Makoni, Pedzisai A, Matafwali, Scott K, Mweetwa, Larry L, Shandele, Ginnethon C, Walker, Roderick B
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Mweetwa, Larry L , Shandele, Ginnethon C , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183161 , vital:43917 , xlink:href="https://doi.org/10.3390/molecules26144244"
- Description: There is a dearth of natural remedies available for the treatment of an increasing number of diseases facing mankind. Natural products may provide an opportunity to produce formulations and therapeutic solutions to address this shortage. Curcumin (CUR), diferuloylmethane; I,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione is the major pigment in turmeric powder which has been reported to exhibit a number of health benefits including, antibacterial, antiviral, anti-cancer, anti-inflammatory and anti-oxidant properties. In this review, the authors attempt to highlight the biological and pharmacological properties of CUR in addition to emphasizing aspects relating to the biosynthesis, encapsulation and therapeutic effects of the compound. The information contained in this review was generated by considering published information in which evidence of enhanced biological and pharmacological properties of nano-encapsulated CUR was reported. CUR has contributed to a significant improvement in melanoma, breast, lung, gastro-intestinal, and genito-urinary cancer therapy. We highlight the impact of nano-encapsulated CUR for efficient inhibition of cell proliferation, even at low concentrations compared to the free CUR when considering anti-proliferation. Furthermore nano-encapsulated CUR exhibited bioactive properties, exerted cytotoxic and anti-oxidant effects by acting on endogenous and cholinergic anti-oxidant systems. CUR was reported to block Hepatitis C virus (HCV) entry into hepatic cells, inhibit MRSA proliferation, enhance wound healing and reduce bacterial load. Nano-encapsulated CUR has also shown bioactive properties when acting on antioxidant systems (endogenous and cholinergic). Future research is necessary and must focus on investigation of encapsulated CUR nano-particles in different models of human pathology.
- Full Text:
- Date Issued: 2021
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Mweetwa, Larry L , Shandele, Ginnethon C , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183161 , vital:43917 , xlink:href="https://doi.org/10.3390/molecules26144244"
- Description: There is a dearth of natural remedies available for the treatment of an increasing number of diseases facing mankind. Natural products may provide an opportunity to produce formulations and therapeutic solutions to address this shortage. Curcumin (CUR), diferuloylmethane; I,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione is the major pigment in turmeric powder which has been reported to exhibit a number of health benefits including, antibacterial, antiviral, anti-cancer, anti-inflammatory and anti-oxidant properties. In this review, the authors attempt to highlight the biological and pharmacological properties of CUR in addition to emphasizing aspects relating to the biosynthesis, encapsulation and therapeutic effects of the compound. The information contained in this review was generated by considering published information in which evidence of enhanced biological and pharmacological properties of nano-encapsulated CUR was reported. CUR has contributed to a significant improvement in melanoma, breast, lung, gastro-intestinal, and genito-urinary cancer therapy. We highlight the impact of nano-encapsulated CUR for efficient inhibition of cell proliferation, even at low concentrations compared to the free CUR when considering anti-proliferation. Furthermore nano-encapsulated CUR exhibited bioactive properties, exerted cytotoxic and anti-oxidant effects by acting on endogenous and cholinergic anti-oxidant systems. CUR was reported to block Hepatitis C virus (HCV) entry into hepatic cells, inhibit MRSA proliferation, enhance wound healing and reduce bacterial load. Nano-encapsulated CUR has also shown bioactive properties when acting on antioxidant systems (endogenous and cholinergic). Future research is necessary and must focus on investigation of encapsulated CUR nano-particles in different models of human pathology.
- Full Text:
- Date Issued: 2021
Nano Co-Crystal Embedded Stimuli-Responsive Hydrogels: A Potential Approach to Treat HIV/AIDS
- Witika, Bwalya A, Stander, Jessé-Clint, Smith, Vincent J, Walker, Roderick B
- Authors: Witika, Bwalya A , Stander, Jessé-Clint , Smith, Vincent J , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183137 , vital:43915 , xlink:href="https://doi.org/10.3390/pharmaceutics13020127"
- Description: Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer–Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.
- Full Text:
- Date Issued: 2021
- Authors: Witika, Bwalya A , Stander, Jessé-Clint , Smith, Vincent J , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183137 , vital:43915 , xlink:href="https://doi.org/10.3390/pharmaceutics13020127"
- Description: Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer–Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.
- Full Text:
- Date Issued: 2021
Preformulation characterization and identification of excipients for nevirapine loaded niosomes
- Witika, Bwalya A, Walker, Roderick B
- Authors: Witika, Bwalya A , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183126 , vital:43914 , xlink:href="https://doi.org/10.1691/ph.2021.0137"
- Description: Nevirapine (NVP) is used for the management of HIV/AIDS but must be dosed frequently, exhibits unpredictable bioavailability and a side effect profile that includes hepato- and dermo-toxicity. Niosomes are a colloidal drug delivery system that may be used to overcome the low bioavailability, side effect profile and frequent dosing needed when using conventional drug delivery systems. The compatibility of NVP with sorbitan esters, polysorbate, cholesterol and dihexadecyl phosphate (DCP) was investigated using Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Fourier Transform Infra-red Spectroscopy (FTIR) and X-ray Powder Diffraction (XRPD). Screening studies were undertaken to identify potential excipients that would produce niosomes with target critical quality attributes (CQA) viz, a particle size (PS) less than 1000 nm, a polydispersity index (PDI) less than 0.500 and an entrapment efficiency greater than 90%. The results revealed that sorbitan esters in combination with cholesterol and 5 μmol DCP produced niosomes with the best CQA and Zeta potential (ZP) less than -30 mV which suggests good stability of the niosomes on storage. Sorbitan esters produced the smallest niosomes of less than 400 nm diameter with a PDI less than 0.400 and an entrapment efficiency of more than 78% without cholesterol. The addition of cholesterol and DCP was essential to form niosomes with target CQA.
- Full Text:
- Date Issued: 2021
- Authors: Witika, Bwalya A , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183126 , vital:43914 , xlink:href="https://doi.org/10.1691/ph.2021.0137"
- Description: Nevirapine (NVP) is used for the management of HIV/AIDS but must be dosed frequently, exhibits unpredictable bioavailability and a side effect profile that includes hepato- and dermo-toxicity. Niosomes are a colloidal drug delivery system that may be used to overcome the low bioavailability, side effect profile and frequent dosing needed when using conventional drug delivery systems. The compatibility of NVP with sorbitan esters, polysorbate, cholesterol and dihexadecyl phosphate (DCP) was investigated using Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Fourier Transform Infra-red Spectroscopy (FTIR) and X-ray Powder Diffraction (XRPD). Screening studies were undertaken to identify potential excipients that would produce niosomes with target critical quality attributes (CQA) viz, a particle size (PS) less than 1000 nm, a polydispersity index (PDI) less than 0.500 and an entrapment efficiency greater than 90%. The results revealed that sorbitan esters in combination with cholesterol and 5 μmol DCP produced niosomes with the best CQA and Zeta potential (ZP) less than -30 mV which suggests good stability of the niosomes on storage. Sorbitan esters produced the smallest niosomes of less than 400 nm diameter with a PDI less than 0.400 and an entrapment efficiency of more than 78% without cholesterol. The addition of cholesterol and DCP was essential to form niosomes with target CQA.
- Full Text:
- Date Issued: 2021
Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal
- Witika, Bwalya A, Smith, Vincent J, Walker, Roderick B
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183172 , vital:43918 , xlink:href="https://doi.org/10.3390/cryst11010033"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiretroviral agents used to manage HIV/AIDS infection. A wet media milling top-down approach was used to develop and produce nano co-crystals of 3TC and AZT. Micro co-crystals were prepared by solvent evaporation and subsequently milled in the presence of two surfactants, viz., sodium lauryl sulfate (SLS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000). Optimisation was undertaken using design of experiments (DoE) and response surface methodology (RSM) to establish and identify parameters that may affect the manufacturing of nano co-crystals. The impact of SLS and TPGS 1000 concentration, milling time, and number of units of milling medium on the manufacturing of nano co-crystals, was investigated. The critical quality attributes (CQA) monitored were particle size (PS), Zeta potential (ZP), and polydispersity index (PDI). Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, transmission electron microscopy, energy dispersive X-ray spectroscopy scanning electron microscopy, and cytotoxicity assays were used for additional characterization of the optimised nano co-crystal. The mean PS, PDI, and ZP of the optimised top-down nanocrystal were 271.0 ± 92.0 nm, 0.467 ± 0.073, and −41.9 ± 3.94 mV, respectively. In conclusion, a simple, inexpensive, rapid, and precise method of nano co-crystal manufacturing was developed, validated, and optimised using DoE and RSM, and the final product exhibited the target CQA.
- Full Text:
- Date Issued: 2021
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183172 , vital:43918 , xlink:href="https://doi.org/10.3390/cryst11010033"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiretroviral agents used to manage HIV/AIDS infection. A wet media milling top-down approach was used to develop and produce nano co-crystals of 3TC and AZT. Micro co-crystals were prepared by solvent evaporation and subsequently milled in the presence of two surfactants, viz., sodium lauryl sulfate (SLS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000). Optimisation was undertaken using design of experiments (DoE) and response surface methodology (RSM) to establish and identify parameters that may affect the manufacturing of nano co-crystals. The impact of SLS and TPGS 1000 concentration, milling time, and number of units of milling medium on the manufacturing of nano co-crystals, was investigated. The critical quality attributes (CQA) monitored were particle size (PS), Zeta potential (ZP), and polydispersity index (PDI). Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, transmission electron microscopy, energy dispersive X-ray spectroscopy scanning electron microscopy, and cytotoxicity assays were used for additional characterization of the optimised nano co-crystal. The mean PS, PDI, and ZP of the optimised top-down nanocrystal were 271.0 ± 92.0 nm, 0.467 ± 0.073, and −41.9 ± 3.94 mV, respectively. In conclusion, a simple, inexpensive, rapid, and precise method of nano co-crystal manufacturing was developed, validated, and optimised using DoE and RSM, and the final product exhibited the target CQA.
- Full Text:
- Date Issued: 2021
A comparative study of the effect of different stabilizers on the critical quality attributes of self-assembling nano co-crystals
- Witika, Bwalya A, Smith, Vincent J, Walker, Roderick B
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183224 , vital:43931 , xlink:href=" https://doi.org/10.3390/pharmaceutics12020182"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used orally to manage HIV/AIDS infection. A pseudo one-solvent bottom-up approach was used to develop and produce nano co-crystals of 3TC and AZT. Equimolar amounts of 3TC dissolved in de-ionized water and AZT in methanol were rapidly injected into a pre-cooled vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer. The particle size, polydispersity index and Zeta potential were elucidated. Further characterization was undertaken using powder X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and energy dispersive X-ray spectroscopy scanning electron microscopy. Different surfactants were assessed for their ability to stabilize the nano co-crystals and for their ability to produce nano co-crystals with specific and desirable critical quality attributes (CQA) including particle size (PS) less than 1000 nm, polydispersity index (PDI) less than 0.500 and Zeta potential (ZP) less than −30 mV. All surfactants produced co-crystals in the nanometer range. The PDI and PS are concentration-dependent for all nano co-crystals manufactured while only ZP was within specification when sodium dodecyl sulfate was used in the process.
- Full Text:
- Date Issued: 2020
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183224 , vital:43931 , xlink:href=" https://doi.org/10.3390/pharmaceutics12020182"
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used orally to manage HIV/AIDS infection. A pseudo one-solvent bottom-up approach was used to develop and produce nano co-crystals of 3TC and AZT. Equimolar amounts of 3TC dissolved in de-ionized water and AZT in methanol were rapidly injected into a pre-cooled vessel and sonicated at 4 °C. The resultant suspensions were characterized using a Zetasizer. The particle size, polydispersity index and Zeta potential were elucidated. Further characterization was undertaken using powder X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and energy dispersive X-ray spectroscopy scanning electron microscopy. Different surfactants were assessed for their ability to stabilize the nano co-crystals and for their ability to produce nano co-crystals with specific and desirable critical quality attributes (CQA) including particle size (PS) less than 1000 nm, polydispersity index (PDI) less than 0.500 and Zeta potential (ZP) less than −30 mV. All surfactants produced co-crystals in the nanometer range. The PDI and PS are concentration-dependent for all nano co-crystals manufactured while only ZP was within specification when sodium dodecyl sulfate was used in the process.
- Full Text:
- Date Issued: 2020
Biocompatibility of biomaterials for nanoencapsulation: Current approaches
- Witika, Bwalya A, Makoni, Pedzisai A, Matafwali, Scott K, Chabalenge, Billy, Mwila, Chiluba, Kalungia, Aubrey C, Nkanga, Christian I, Bapolisi, Alain M, Walker, Roderick B
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Chabalenge, Billy , Mwila, Chiluba , Kalungia, Aubrey C , Nkanga, Christian I , Bapolisi, Alain M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183289 , vital:43939 , xlink:href="https://doi.org/10.3390/nano10091649"
- Description: Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed.
- Full Text:
- Date Issued: 2020
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Matafwali, Scott K , Chabalenge, Billy , Mwila, Chiluba , Kalungia, Aubrey C , Nkanga, Christian I , Bapolisi, Alain M , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183289 , vital:43939 , xlink:href="https://doi.org/10.3390/nano10091649"
- Description: Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed.
- Full Text:
- Date Issued: 2020
Nano-biomimetic drug delivery vehicles: Potential approaches for COVID-19 treatment
- Witika, Bwalya A, Makoni, Pedzisai A, Mweetwa, Larry L, Ntemi, Pascal V, Chikukwa, Mellisa T R, Matafwali, Scott K, Mwila, Chiluba, Mudenda, Steward, Katandula, Jonathan, Walker, Roderick B
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Mweetwa, Larry L , Ntemi, Pascal V , Chikukwa, Mellisa T R , Matafwali, Scott K , Mwila, Chiluba , Mudenda, Steward , Katandula, Jonathan , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183440 , vital:43991 , xlink:href="https://doi.org/10.3390/molecules25245952"
- Description: The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a "Trojan horse" for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.
- Full Text:
- Date Issued: 2020
- Authors: Witika, Bwalya A , Makoni, Pedzisai A , Mweetwa, Larry L , Ntemi, Pascal V , Chikukwa, Mellisa T R , Matafwali, Scott K , Mwila, Chiluba , Mudenda, Steward , Katandula, Jonathan , Walker, Roderick B
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183440 , vital:43991 , xlink:href="https://doi.org/10.3390/molecules25245952"
- Description: The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a "Trojan horse" for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.
- Full Text:
- Date Issued: 2020
Quality by Design Optimization of Cold Sonochemical Synthesis of Zidovudine-Lamivudine Nanosuspensions:
- Witika, Bwalya A, Smith, Vincent J, Walker, Roderick B
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148424 , vital:38738 , https://doi.org/10.3390/pharmaceutics12040367
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used to manage HIV/AIDS infection. The compounds require frequent dosing, exhibit unpredictable bioavailability and a side effect profile that includes hepato- and haema-toxicity. A novel pseudo one-solvent bottom-up approach and Design of Experiments using sodium dodecyl sulphate (SDS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000) to electrosterically stablize the nano co-crystals was used to develop, produce and optimize 3TC and AZT nano co-crystals. Equimolar solutions of 3TC in surfactant dissolved in de-ionised water and AZT in methanol were rapidly injected into a vessel and sonicated at 4 °C.
- Full Text:
- Date Issued: 2020
- Authors: Witika, Bwalya A , Smith, Vincent J , Walker, Roderick B
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148424 , vital:38738 , https://doi.org/10.3390/pharmaceutics12040367
- Description: Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used to manage HIV/AIDS infection. The compounds require frequent dosing, exhibit unpredictable bioavailability and a side effect profile that includes hepato- and haema-toxicity. A novel pseudo one-solvent bottom-up approach and Design of Experiments using sodium dodecyl sulphate (SDS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000) to electrosterically stablize the nano co-crystals was used to develop, produce and optimize 3TC and AZT nano co-crystals. Equimolar solutions of 3TC in surfactant dissolved in de-ionised water and AZT in methanol were rapidly injected into a vessel and sonicated at 4 °C.
- Full Text:
- Date Issued: 2020
Development, manufacture and characterization of niosomes for the delivery for nevirapine
- Witika, Bwalya A, Walker, Roderick B
- Authors: Witika, Bwalya A , Walker, Roderick B
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183514 , vital:44002 , xlink:href="https://doi.org/10.1691/ph.2019.8168"
- Description: Nevirapine (NVP), used for the treatment of HIV/AIDS, exhibits unpredictable oral bioavailability, has a poor side effect profile and requires frequent dosing. Niosomes are novel drug delivery systems that have the potential to overcome these challenges. A thin layer hydration approach was used to produce niosomes and optimisation was undertaken using design of experiments (DoE) and response surface methodology (RSM) establish and identify parameters that may affect the manufacture of niosomes. The impact of cholesterol and surfactant content, hydration time and temperature on manufacture was investigated. Critical quality attributes (CQA) in respect of particle size (PS), entrapment efficiency (EE), polydispersity index (PDI) and the amount of NVP released at 48 hours was also assessed. The optimised niosome composition was identified and manufactured and the CQA characterised prior to placing the batch on stability for 12 weeks at 4±2 °C and 22±2 °C. The PS, PDI, EE and % NVP released at 48 h was 523.36±23.16 nm, 0.386±0.054, 96.8 % and 25.3 % for niosomes manufactured with Span® 20. Similarly, the parameters were 502.87±21.77 nm and 0.394±0.027, 98.0 % and 25.0 % for mean PS, PDI, EE and %NVP released at 48 h for Span® 80 niosomes. All characterisation was undertaken on the day of manufacture. In conclusion, a simple, cheap, rapid and precise method of manufacture of NVP niosomes was developed, validated and optimised using DoE and RSM and the product exhibited the target CQA.
- Full Text:
- Date Issued: 2019
- Authors: Witika, Bwalya A , Walker, Roderick B
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183514 , vital:44002 , xlink:href="https://doi.org/10.1691/ph.2019.8168"
- Description: Nevirapine (NVP), used for the treatment of HIV/AIDS, exhibits unpredictable oral bioavailability, has a poor side effect profile and requires frequent dosing. Niosomes are novel drug delivery systems that have the potential to overcome these challenges. A thin layer hydration approach was used to produce niosomes and optimisation was undertaken using design of experiments (DoE) and response surface methodology (RSM) establish and identify parameters that may affect the manufacture of niosomes. The impact of cholesterol and surfactant content, hydration time and temperature on manufacture was investigated. Critical quality attributes (CQA) in respect of particle size (PS), entrapment efficiency (EE), polydispersity index (PDI) and the amount of NVP released at 48 hours was also assessed. The optimised niosome composition was identified and manufactured and the CQA characterised prior to placing the batch on stability for 12 weeks at 4±2 °C and 22±2 °C. The PS, PDI, EE and % NVP released at 48 h was 523.36±23.16 nm, 0.386±0.054, 96.8 % and 25.3 % for niosomes manufactured with Span® 20. Similarly, the parameters were 502.87±21.77 nm and 0.394±0.027, 98.0 % and 25.0 % for mean PS, PDI, EE and %NVP released at 48 h for Span® 80 niosomes. All characterisation was undertaken on the day of manufacture. In conclusion, a simple, cheap, rapid and precise method of manufacture of NVP niosomes was developed, validated and optimised using DoE and RSM and the product exhibited the target CQA.
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- Date Issued: 2019
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