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
Muco-adhesive clarithromycin-loaded nanostructured lipid carriers for ocular delivery: Formulation, characterization, cytotoxicity and stability
- Makoni, Pedzisai A, Khamanga, Sandile M, Walker, Roderick B
- Authors: Makoni, Pedzisai A , Khamanga, Sandile M , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183150 , vital:43916 , xlink:href="https://doi.org/10.1016/j.jddst.2020.102171"
- Description: Topical ophthalmic formulations are the preferred approach to treat the anterior segment of the eye as it is a non-invasive therapeutic approach. The ocular bioavailability of drugs is generally limited, due to the presence of impervious anatomical barriers and low residence time and contact with the target tissue. Optimization of clarithromycin-loaded nanostructured lipid carriers using Design of Experiments was undertaken. Manufacture of nanostructured lipid carriers was achieved using hot emulsification ultrasonication. Formulation and process parameters were successfully identified following screening and subsequently optimized using Tween® 20, as a stabilizer. Muco-adhesive properties that could potentially increase ocular residence time, in vitro clarithromycin release and cytotoxicity against HeLa cells were evaluated. Short term stability studies of the optimized lipidic formulations was assessed at 4 °C and 22 °C. The optimized formulation exhibited muco-adhesive properties under stationary conditions assessed using Laser Doppler Anemometry, sustained release of API over 24 h under in vitro conditions. In vitro cytotoxicity studies revealed that the NLC were less cytotoxic to HeLa cells in comparison to pure API. The results suggest that the optimized carriers may have the potential to enhance precorneal retention, increase ocular availability and permit dose reduction or permit use of a longer dosing frequency.
- Full Text:
- Date Issued: 2021
- Authors: Makoni, Pedzisai A , Khamanga, Sandile M , Walker, Roderick B
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183150 , vital:43916 , xlink:href="https://doi.org/10.1016/j.jddst.2020.102171"
- Description: Topical ophthalmic formulations are the preferred approach to treat the anterior segment of the eye as it is a non-invasive therapeutic approach. The ocular bioavailability of drugs is generally limited, due to the presence of impervious anatomical barriers and low residence time and contact with the target tissue. Optimization of clarithromycin-loaded nanostructured lipid carriers using Design of Experiments was undertaken. Manufacture of nanostructured lipid carriers was achieved using hot emulsification ultrasonication. Formulation and process parameters were successfully identified following screening and subsequently optimized using Tween® 20, as a stabilizer. Muco-adhesive properties that could potentially increase ocular residence time, in vitro clarithromycin release and cytotoxicity against HeLa cells were evaluated. Short term stability studies of the optimized lipidic formulations was assessed at 4 °C and 22 °C. The optimized formulation exhibited muco-adhesive properties under stationary conditions assessed using Laser Doppler Anemometry, sustained release of API over 24 h under in vitro conditions. In vitro cytotoxicity studies revealed that the NLC were less cytotoxic to HeLa cells in comparison to pure API. The results suggest that the optimized carriers may have the potential to enhance precorneal retention, increase ocular availability and permit dose reduction or permit use of a longer dosing frequency.
- 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
Ultrasound-Triggered Release of 5-Fluorouracil from Soy Lecithin Echogenic Liposomes
- Ezekiel, Charles I, Bapolisi, Alain M, Walker, Roderick B, Krause, Rui W M
- Authors: Ezekiel, Charles I , Bapolisi, Alain M , Walker, Roderick B , Krause, Rui W M
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183115 , vital:43913 , xlink:href="https://doi.org/10.3390/pharmaceutics13060821"
- Description: Colorectal cancer is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) has been the major chemotherapeutic treatment for colorectal cancer patients. However, the efficacy of 5-FU is limited by drug resistance, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying the need for improvement of the therapeutic index. In this study, the effects of ultrasound on echogenic 5-FU encapsulated crude soy liposomes were investigated for their potential to address these challenges. Liposomes were prepared by thin-film hydration using crude soy lecithin and cholesterol. Argon gas was entrapped in the liposomes for sonosensitivity (that is, responsiveness to ultrasound). The nanoparticles were characterized for particle size and morphology. The physicochemical properties were also evaluated using differential scanning calorimetry, Fourier transform infrared and X-ray diffraction. The release profile of 5-FU was assessed with and without 20 kHz low-frequency ultrasound waves at various amplitudes and exposure times. The result reveal that 5-FU-loaded liposomes were spherical with an encapsulation efficiency of approximately 60%. Approximately 65% of 5-FU was released at the highest amplitude and exposure time was investigated. The results are encouraging for the stimulated and controlled release of 5-FU for the management of colorectal cancer.
- Full Text:
- Date Issued: 2021
- Authors: Ezekiel, Charles I , Bapolisi, Alain M , Walker, Roderick B , Krause, Rui W M
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/183115 , vital:43913 , xlink:href="https://doi.org/10.3390/pharmaceutics13060821"
- Description: Colorectal cancer is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) has been the major chemotherapeutic treatment for colorectal cancer patients. However, the efficacy of 5-FU is limited by drug resistance, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying the need for improvement of the therapeutic index. In this study, the effects of ultrasound on echogenic 5-FU encapsulated crude soy liposomes were investigated for their potential to address these challenges. Liposomes were prepared by thin-film hydration using crude soy lecithin and cholesterol. Argon gas was entrapped in the liposomes for sonosensitivity (that is, responsiveness to ultrasound). The nanoparticles were characterized for particle size and morphology. The physicochemical properties were also evaluated using differential scanning calorimetry, Fourier transform infrared and X-ray diffraction. The release profile of 5-FU was assessed with and without 20 kHz low-frequency ultrasound waves at various amplitudes and exposure times. The result reveal that 5-FU-loaded liposomes were spherical with an encapsulation efficiency of approximately 60%. Approximately 65% of 5-FU was released at the highest amplitude and exposure time was investigated. The results are encouraging for the stimulated and controlled release of 5-FU for the management of colorectal cancer.
- Full Text:
- Date Issued: 2021
- «
- ‹
- 1
- ›
- »