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Background While Africa accounts for a significant proportion of world population, and disease and injury burden, it produces less than 1% of the total research output within emergency care. Emergency care research capacity in Africa may... more
Background While Africa accounts for a significant proportion of world population, and disease and injury burden, it produces less than 1% of the total research output within emergency care. Emergency care research capacity in Africa may be expanded through the development of doctoral programmes that aim to upskill the PhD student into an independent scholar, through dedicated support and structured learning. This study therefore aims to identify the nature of the problem of doctoral education in Africa, thereby informing a general needs assessment within the context of academic emergency medicine. Methods A scoping review, utilising an a priori, piloted search strategy was conducted (Medline via PubMed and Scopus) to identify literature published between 2011 and 2021 related to African emergency medicine doctoral education. Failing that, an expanded search was planned that focused on doctoral education within health sciences more broadly. Titles, abstracts, and full texts were scr...
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Background: Pre-hospital emergency care providers working in emergency medical services (EMS) are licenced to administer medication to the acutely ill and injured. In South Africa, there are significant seasonal variations in temperature,... more
Background: Pre-hospital emergency care providers working in emergency medical services (EMS) are licenced to administer medication to the acutely ill and injured. In South Africa, there are significant seasonal variations in temperature, sometimes far exceeding the recommended medication storage temperature. The aim of this study was to determine the summer temperature ranges inside select emergency vehicles and storage facilities in four provinces in South Africa. Methods: A prospective, observational study was conducted in four (Cape Town, Western Cape; Johannesburg, Gauteng; Durban, KwaZulu-Natal; Potchefstroom, North West) provinces during the summer (February – March) months of 2019. A continuous temperature monitoring device was placed in the medication storage room, the response vehicle drug bags, and an ambulance at a single private EMS base in each of the provinces. Temperature data were recorded in fifteen-minute intervals. The data were extracted after six weeks and subj...
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The aim of the present study was to formulate a nanosuspension (FA-NS) of fusidic acid (FA) to enhance its aqueous solubility and antibacterial activity. The nanosuspension was characterized using various in vitro, in silico, and in vivo... more
The aim of the present study was to formulate a nanosuspension (FA-NS) of fusidic acid (FA) to enhance its aqueous solubility and antibacterial activity. The nanosuspension was characterized using various in vitro, in silico, and in vivo techniques. The size, polydispersity index, and zeta potential of the optimized FA-NS were 265 ± 2.25 nm, 0.158 ± 0.026, and -16.9 ± 0.794 mV, respectively. The molecular dynamics simulation of FA and Poloxamer-188 showed an interaction and binding energy of -74.42 kJ/mol and -49.764 ± 1.298 kJ/mol, respectively, with van der Waals interactions playing a major role in the spontaneous binding. There was an 8-fold increase in the solubility of FA in a nanosuspension compared to the bare drug. The MTT assays showed a cell viability of 75-100% confirming the nontoxic nature of FA-NS. In vitro antibacterial activity revealed a 16- and 18-fold enhanced activity against Staphylococcus aureus (SA) and methicillin-resistant SA (MRSA), respectively, when comp...
Research Interests: Biochemistry, Microbiology, Biophysics, Chemistry, Biotechnology, and 15 moreCancer, Cell Biology, Medicine, Molecular Dynamics Simulations, Cell Viability, Antibacterial activity, In Vivo, Binding Energy, Nanosuspension, Fusidic Acid, Dynamics Simulation, MIC, Kj, Molecular Pharmaceutics, and Minimum Inhibitory Concentration
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Abstract This work reports two new classes of non-toxic heterocyclic quaternary ammonium surfactants (HQASs) synthesized by condensation of a series of fatty acids with 2-morpholinoethan-1-amine and pyridin-4-ylmethanamine, followed by... more
Abstract This work reports two new classes of non-toxic heterocyclic quaternary ammonium surfactants (HQASs) synthesized by condensation of a series of fatty acids with 2-morpholinoethan-1-amine and pyridin-4-ylmethanamine, followed by quaternization with benzyl bromide. Their critical micelle concentration (CMC), Krafft temperature ( Tk ), emulsion stability and foaming properties were determined. The CMC values of HQASs ranged from 0.24 to 0.55 mM/L. In vitro antibacterial activity studies revealed that the HQASs possessing unsaturated hydrocarbon chains exhibited activity against all the tested bacteria (minimum inhibitory concentration = 31.25–500 μg/mL) whereas, those possessing saturated hydrocarbon chains did not exhibit any activity.
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The design and synthesis of novel pH-responsive nanoantibiotics is an emerging research area to address the antibiotic resistance crisis. The purpose of this study was therefore to synthesize a new anionic gemini surfactant (AGS) that... more
The design and synthesis of novel pH-responsive nanoantibiotics is an emerging research area to address the antibiotic resistance crisis. The purpose of this study was therefore to synthesize a new anionic gemini surfactant (AGS) that could result in the formulation of pH-responsive chitosan nanoparticles (CSNPs) to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. The coupling of oleic acid with 2,2-dimethyl-5,5-bis(hydroxymethyl)-1,3-dioxane and subsequent deprotection followed by a reaction with succinic anhydride and sodium bicarbonate yielded AGS. Critical micelle concentration (CMC) was determined using conductometry and in vitro cytotoxicity was performed using a MTT assay. Vancomycin loaded CSNPs containing AGS (DL_CSSNPs) were prepared by ionotropic gelation of chitosan with pentasodium tripolyphosphate. CSNPs were characterized for size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, in vitro drug release and ...
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Solubility enhancement of poorly soluble antibiotics via self-assembling nano systems could be a promising approach to effectively treat bacterial infections in the current scenario of evolving resistant species.
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An acid cleavable lipid (SA-3M) was synthesized and used to develop pH-responsive solid lipid nanoparticles (SLNs) to deliver vancomycin base (VM-FB) to acidic infection sites. The size, polydispersity index and zeta potential of... more
An acid cleavable lipid (SA-3M) was synthesized and used to develop pH-responsive solid lipid nanoparticles (SLNs) to deliver vancomycin base (VM-FB) to acidic infection sites. The size, polydispersity index and zeta potential of VM-FB_SA-3M_SLNs were 132.9±9.1nm, 0.159±0.01 and -26±4.4mV respectively, with 57.80±1.1% encapsulation efficiency. VM-FB release was significantly faster at pH6.5 than pH7.4. In vitro antibacterial activity against methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA) revealed that SLNs had enhanced activity at pH6.5 than pH7.4. In vivo study showed that the amount of MRSA remaining in the skin of VM-FB_SA-3M_SLNs treated mice was approximately 22-fold lower than VM-FB treated mice. Histological investigations revealed that signs of inflammation in the skin treated with VM-FB_SA-3M_SLNs were minimal. In conclusion, this study confirmed that SA-3M can form pH-responsive SLNs capable of releasing antibiotic specifically at acidic infect...
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The purpose of this study was to explore the preparation of a new lipid-dendrimer hybrid nanoparticle (LDHN) system to effectively deliver vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) infections. Spherical LDHNs... more
The purpose of this study was to explore the preparation of a new lipid-dendrimer hybrid nanoparticle (LDHN) system to effectively deliver vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) infections. Spherical LDHNs with particle size, polydispersity index and zeta potential of 52.21±0.22nm, 0.105±0.01, and -14.2±1.49mV respectively were prepared by hot stirring and ultrasonication using Compritol 888 ATO, G4 PAMAM- succinamic acid dendrimer, and Kolliphor RH-40. Vancomycin encapsulation efficiency (%) in LDHNs was almost 4.5-fold greater than in lipid-polymer hybrid nanoparticles formulated using Eudragit RS 100. Differential scanning calorimetry and Fourier transform-infrared studies confirmed the formation of LDHNs. The interactions between the drug-dendrimer complex and lipid molecules using in silico modeling revealed the molecular mechanism behind the enhanced encapsulation and stability. Vancomycin was released from LDHNs over the period of 72h with zero order kinetics and super case II transport mechanism. The minimum inhibitory concentration (MIC) against S. aureus and MRSA were 15.62μg/ml and 7.81μg/ml respectively. Formulation showed sustained activity with MIC of 62.5μg/ml against S. aureus and 500μg/ml against MRSA at the end of 72 and 54h period respectively. The results suggest that the LDHN system can be an effective strategy to combat resistant infections.
Research Interests: Chemistry, Nanoparticles, Medicine, Dendrimers, Pharmaceutics, and 13 moreVancomycin, Computer Simulation, Fatty acids, Differential scanning calorimetry, Staphylococcus aureus, Anti-Bacterial Agents, Microbial Sensitivity Tests, Zeta Potential, Drug Carriers, Dendrimer, Dispersity, Pharmacology and pharmaceutical sciences, and Minimum Inhibitory Concentration
Research Interests: Materials Science, Thermodynamics, Biomedical Engineering, Polyelectrolytes, Nanoparticles, and 15 moreMedicine, Vancomycin, Humans, Differential scanning calorimetry, Staphylococcus aureus, Anti-Bacterial Agents, X ray diffraction, HeLa cells, Molecular Conformation, Zeta Potential, Drug Carriers, Cell Survival, Polyelectrolyte, Methicillin Resistant Staphylococcus Aureus, and MTT assay
New and effective strategies to transform current antimicrobials are required to address the increasing issue of microbial resistance and declining introduction of new antibiotic drugs. In this context, metal complexes of known drugs and... more
New and effective strategies to transform current antimicrobials are required to address the increasing issue of microbial resistance and declining introduction of new antibiotic drugs. In this context, metal complexes of known drugs and nano delivery systems for antibiotics are proving to be promising strategies. The aim of the study was therefore to synthesize a silver complex of clotrimazole and formulate it into a nano delivery system for enhanced and sustained antibacterial activity against susceptible and resistant Staphylococcus aureus. A silver complex of clotrimazole was synthesized, characterized and further encapsulated into solid lipid nanoparticles to evaluate its antibacterial activity against S. aureus and methicillin-resistant S. aureus (MRSA). An in vitro cytotoxicity study was performed on HepG2 cell lines to assess the overall biosafety of the synthesized clotrimazole silver complex to mammalian cells, and was found to be non-toxic to mammalian cells (cell viability >80%). The minimum inhibitory concentrations (MIC) of clotrimazole and clotrimazole-silver were 31.25 and 9.76μg/mL against S. aureus, and 31.25 and 15.62 against MRSA, respectively. Clotrimazole SLNs exhibited MIC values of 104 and 208μg/mL against both MSSA and MRSA at the end of 18 and 36h, respectively, but thereafter completely lost its antibacterial activity. Clotrimazole-silver SLNs had an MIC value of 52μg/mL up to 54h, after which the MIC value was 104μg/mL against both strains at the end of 72h. Thus, clotrimazole-silver SLNs was found to be an efficient nanoantibiotic.
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Schematic of formation of linoleic acid nanoemulsion.
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Novel dendritic ester derivatives of unsaturated fatty acids as potential transdermal permeation enhancers.
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In this study the newly synthesised PETIM silver salts displayed a low toxicity level and showed significant antimicrobial activity against both sensitive (S. aureus) and resistant (MRSA) bacterial strains.
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Although buccal permeation investigations with antiretroviral drug solutions have confirmed their transbuccal delivery potential, studies on their formulation into delivery systems are lacking. Multipolymeric monolayered films (MMFs) with... more
Although buccal permeation investigations with antiretroviral drug solutions have confirmed their transbuccal delivery potential, studies on their formulation into delivery systems are lacking. Multipolymeric monolayered films (MMFs) with drugs and polymers of opposing solubilities will offer several advantages for the controlled release delivery of didanosine (DDI) via the buccal route. The aim of this study was to employ a co-blending-co-plasticization technique for preparation of MMFs containing Eudragit(®) RS 100 (EUD) and Hydroxypropyl methylcellulose (HPMC) and to undertake molecular modelling and in vitro characterizations. Uniform drug content (91-105%) with low variability was obtained for all films. Co-blending of DDI:HPMC:EUD (1:1:10) was required to achieve controlled drug release. The buccal permeability potential of DDI from the MMFs was successfully demonstrated with a permeability coefficient of 0.72±0.14×10(-2) cm/h and a steady state flux of 71.63±13.54 μg/cm(2) h....
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This study identified and compared the buccal permeability properties of antiretroviral drugs, didanosine (ddI) and tenofovir (TNF), and the permeability effects of polymeric excipients - i.e. carboxymethylcellulose (CMC), sodium alginate... more
This study identified and compared the buccal permeability properties of antiretroviral drugs, didanosine (ddI) and tenofovir (TNF), and the permeability effects of polymeric excipients - i.e. carboxymethylcellulose (CMC), sodium alginate (SA), polyacrylic acid (PAA) and polyethylene glycol (PEG) - as potential multifunctional excipients for buccal drug delivery. Permeation studies across porcine buccal mucosa were performed and the drug was quantified using UV spectrophotometry. The mean flux for both ddI (113-181 µg/cm(2)h) and TNF (40-102 µg/cm(2)h) increased linearly with increasing donor concentration. All polymeric excipients improved permeability of TNF while only PEG was effective for ddI. Permeability enhancement ratios at 20 mg/mL for ddI and TNF were 1.63 and 1.74, respectively, using PEG (0.5% w/v) and CMC (0.5% w/v), respectively. The maximum enhancement ratio of 2.13 for TNF was achieved with 4% w/v PEG. Light and transmission electron microscopy revealed no significant loss in cellular integrity of mucosa treated with either TNF or ddI alone or when coupled with PEG as a polymeric enhancer. Histomorphological observations correlated with flux values obtained for TNF and ddI alone, as well as with PEG's effects on drug mass flux. TNF and ddI have demonstrated buccal delivery potential. Selective polymeric excipients provide an effective means to increase their penetration and may serve as potential formulation multifunctional excipients in a delivery system for delivery via the buccal route.
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Saquinavir (SQV), a candidate for buccal drug delivery, is limited by poor solubility. This study identified the effects of high-energy ball milling on the buccal permeability of SQV and compared it to the effects of chemical enhancers,... more
Saquinavir (SQV), a candidate for buccal drug delivery, is limited by poor solubility. This study identified the effects of high-energy ball milling on the buccal permeability of SQV and compared it to the effects of chemical enhancers, i.e. ethylenediaminetetraacetic acid (EDTA), sodium lauryl sulfate (SLS), polyethylene glycol (PEG) and beta cyclodextrin (β-cyclodextrin). SQV was ball milled using a high energy planetary mill (1, 3, 15 and 30 h) and permeation studies across porcine buccal mucosa were performed using franz diffusion cells. Drug was quantified by UV spectrophotometry. Both unmilled and milled SQV samples were able to permeate the buccal mucosa. Milled samples of 15 h displayed the greatest flux of 10.40 ± 1.24 µg/cm(2 )h and an enhancement ratio of 2.61. All enhancers were able to increase the buccal permeability of unmilled SQV, with SLS achieving the greatest flux (6.99 ± 0.7 µg/cm(2)) and an enhancement ratio of 1.75. However, all the milled SQV samples displayed greater permeability than SLS, the best chemical enhancer for unmilled SQV. Enhanced permeability by ball milling was attributed to reduction in particle size, formation of solid dispersions and an increase in solubility of milled samples. Microscopical evaluation revealed no significant loss in mucosal cellular integrity treated with either unmilled or milled SQV. Histological studies suggest that SQV uses both the paracellular and transcellular route of transport across the mucosa, with drug treatment having no permanent affects. High-energy ball milling was superior to the chemical enhancers studied for enhancement of SQV buccal permeation.
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A novel AB2-type amphiphilic block copolymer [OA-C=N-NH-(PEG)2] with hydrazone linkage was synthesized and explored for pH-triggered antibiotic delivery. Vancomycin (VCM) loaded micelles of the polymer [OA-C=N-NH-(PEG)2-VCM] were... more
A novel AB2-type amphiphilic block copolymer [OA-C=N-NH-(PEG)2] with hydrazone linkage was synthesized and explored for pH-triggered antibiotic delivery. Vancomycin (VCM) loaded micelles of the polymer [OA-C=N-NH-(PEG)2-VCM] were spherical in shape with size, polydispersity index, zeta potential and entrapment efficiency of 130.33±7.36 nm, 0.163±0.009, -4.33±0.55 mV and 39.61±4.01 % respectively. The dilution stability study exhibited no significant change in the size distribution of OA-C=N-NH-(PEG)2-VCM micelles up to 320-fold dilution. An in vitro drug release assay confirmed greater release of VCM from OA-C=N-NH-(PEG)2-VCM at pH 6, compared to pH 7.4. An in vitro antibacterial activity evaluation of OA-C=N-NH-(PEG)2-VCM showed 2-fold enhancement in antibacterial activity of VCM after 54 h of incubation against Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) at acidic pH compared to physiological pH. An in vivo antibacterial activity of OA-C=N-NH-(PEG)2-VCM further proved the enhanced activity of OA-C=N-NH-(PEG)2-VCM against MRSA. In conclusion, micelles from pH-responsive OA-C=N-NH-(PEG)2 could be utilized for site-specific delivery of VCM at the infection site.