Sipho Mdanda - Academia.edu (original) (raw)

Papers by Sipho Mdanda

Antibiotics

Virulent Enterobacterale strains expressing serine and metallo-β-lactamases (MBL) genes have emer... more Virulent Enterobacterale strains expressing serine and metallo-β-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop β-lactamase inhibitors to counter this resistance. Currently, serine β-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-β-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived β-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of ≤1 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 µM and 30.9 µM against New Delhi Metallo-β-lactamase (NDM-1) and ...

FEMS Microbiology Letters

The recent surge in beta-lactamase resistance has created superbugs, which pose a current and sig... more The recent surge in beta-lactamase resistance has created superbugs, which pose a current and significant threat to public healthcare. This has created an urgent need to keep pace with the discovery of inhibitors that can inactivate these beta-lactamase producers. In this study, the in vitro and in vivo activity of 1,4,7-triazacyclononane-1,4,7 triacetic acid (NOTA)—a potential metallo-beta-lactamase (MBL) inhibitor was evaluated in combination with meropenem against MBL producing bacteria. Time–kill studies showed that NOTA restored the efficacy of meropenem against all bacterial strains tested. A murine infection model was then used to study the in vivo pharmacokinetics and efficacy of this metal chelator. The coadministration of NOTA and meropenem (100 mg/kg.bw each) resulted in a significant decrease in the colony-forming units of Klebsiella pneumoniae NDM-1 over an 8-h treatment period (>3 log10 units). The findings suggest that chelators, such as NOTA, hold strong potential...

Nanofabrication

The purpose of this study was to synthesize duloxetine (DLX)- loaded Eudragit-Chitosan (Eud-CHT) ... more The purpose of this study was to synthesize duloxetine (DLX)- loaded Eudragit-Chitosan (Eud-CHT) nanoparticles enclosed in an oral gelatin capsule and to evaluate the potential to transport DLX to the blood-brain barrier (BBB)for improved neuro-availability. The utilization of Eudragit® with chitosan offers a pH-dependent controlled drug release. The physicochemical properties of the formulated DLX-loaded Eud-CHT nanosystem were confirmed using various characterization techniques. SEM confirmed the nanoparticle morphology and pore size distribution. The particle size was 100 ± 73,41 nm, with a polydispersity index (PDI) of 0,283 and zeta potential of 16±2,79 mV. Drug entrapment efficacy (DEE) of 72% was attained, and molecular modelling predicted an efficient and controllable drug delivery system. The release of DLX from the nanosystem was evaluated at pH1.2, pH 6.8 and pH 7.4. At a pH of 6.8, 40 % of DLX was released, with only 20 % at pH 1.2 and 35% at pH 7.4. This demonstrated DL...

South African Journal of Chemistry

The COVID-19 pandemic has resulted in an unprecedented surge in the demand for alcohol-based hand... more The COVID-19 pandemic has resulted in an unprecedented surge in the demand for alcohol-based hand sanitisers (ABHS). The Centre for Disease Control (CDC) and World Health Organisation (WHO) recommend alcohol, i.e., isopropanol or ethanol, at a 60-95% concentration in ABHS for sufficient antiviral protection. Consumers need to be vigilant of substandard hand sanitisers being marketed to the public. The frequent exposure of microorganisms to alcohol concentrations below the recommended range for infection prevention may lead to resistant mutations, and above the range may be ineffective. Therefore, this study aimed to verify the stated alcohol content in hand sanitisers from their respective labels. We analysed 50 hand sanitiser samples available to our region in Durban, KwaZulu-Natal, South Africa, using a Shimadzu GC-MS-QP2010 Ultra equipped with a Zebron ZB-wax capillary column. The hand sanitisers analysed had a range of 44-93% alcohol content. The data from our study also reveale...

Naicker for their invaluable inputs, initiatives and guidance. I learnt hard work, tenacity and h... more Naicker for their invaluable inputs, initiatives and guidance. I learnt hard work, tenacity and humility from you all. I especially appreciate Tricia for her uncommon understanding and her high level of emotional intelligence.

Pharmaceutics

As one of the most cutting-edge and promising polymer crosslinked network nanoparticle systems. P... more As one of the most cutting-edge and promising polymer crosslinked network nanoparticle systems. Polymer nano-sized hydrogels (nanogels) have been a hot topic in the biomedical field over the last few decades. Due to their unique characteristics, which include their relatively high drug encapsulation efficiency, ease of preparation, high tunability, low toxicity, high stability in serum and responsive behavior to a range of stimuli to facilitate drug release. Nanogels are thought to be the next generation of drug delivery systems that can completely change the way that drug delivery systems have an impact on patients’ lives. Nanogels have demonstrated significant potential in a variety of fields, including chemotherapy, diagnosis, organ targeting, and delivery of bioactive molecules of different dimensions. However, the lack of substantial clinical data from nanogels becomes one of the major barriers to translating the nanogel concept into a practical therapeutic application for many...

Biomedicines

High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of c... more High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of cancers in both adults and children. However, the toxicity associated with HDMTX has resulted in the spread of infections and treatment interruption. Further, poor bioavailability due to efflux pump activities mediated by P-glycoprotein has also been linked to poor therapeutic effects of methotrexate following oral administrations. D-α-Tocopheryl poly-ethylene glycol 1000 succinate (TPGS) is known to improve the bioavailability of poorly soluble drugs by inhibiting P-gp efflux activities, thus enhancing cellular uptake. Therefore, to achieve improved bioavailability for MTX, this study aimed to design and develop a novel drug delivery system employing TPGS and a biodegradable polymer, i.e., PLGA, to construct methotrexate-loaded nanoparticles fixated in alginate-gelatine 3D printable hydrogel ink to form a solid 3D printed tablet for oral delivery. The results indicated that high accuracy...

Polymers

Psoriasis vulgaris (PV) is a common chronic disease, affecting much of the population. Hydrocorti... more Psoriasis vulgaris (PV) is a common chronic disease, affecting much of the population. Hydrocortisone (HCT) is currently utilized as a PV treatment; however, it is associated with undesirable side effects. The aim of this research was to create a thermo-responsive nano-hydrogel delivery system. HCT-loaded sorbitan monostearate (SMS)-polycaprolactone (PCL) nanoparticles, encapsulated with thermo-responsive hydrogel carboxymethyl cellulose (CMC), were synthesized by applying the interfacial polymer-deposition method following solvent displacement. The nanoparticles’ properties were evaluated employing Differential Scanning Colorimetry, Thermogravimetric Analysis, Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Zeta sizer, Ultraviolet/Visual spectroscopy, and cytotoxicity testing. The nanoparticle sizes were 110.5 nm, with polydispersity index of 0.15 and zeta potential of −58.7 mV. A drug-entrapment efficacy of 76% was attained by the HCT-loaded SMS-PCL nanopart...

Polymers

In many clinical applications, the transdermal route is used as an alternative approach to avoid ... more In many clinical applications, the transdermal route is used as an alternative approach to avoid the significant limitations associated with oral drug delivery. There is a long history for drug delivery through the skin utilizing transdermal microneedle arrays. Microneedles are reported to be versatile and very efficient devices. This technique has spurred both industrial and scientific curiosity, due to its outstanding characteristics such as painless penetration, affordability, excellent medicinal efficiency, and relative protection. Microneedles possess outstanding properties for diverse biomedical uses such as the delivery of very large substances with ionic and hydrophilic physicochemical properties. Importantly, microneedles are applicable in numerous biomedical fields such as therapy, diagnosis, and vaccine administration. Microneedles are emerging tools that have shown profound potential for biomedical applications. Transdermal microneedle technologies are likely to become a...

ACS Omega

Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths... more Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths can be prevented through the timely administration of naloxone (NLX), a nonselective mu (μ)-, kappa (κ)-, and delta (δ)-opioid receptor antagonist. NLX competitively inhibits opioid-overdose-induced respiratory depression without eliciting any narcotic effect itself. The aim of this study was to investigate the antagonistic action of NLX by comparing its distribution to that of 6-monacetylmorphine (6-MAM), heroin's major metabolite, in a rodent model using mass spectrometric imaging (MSI) in combination with liquid chromatography−tandem mass spectrometry (LC−MS/MS). Male Sprague−Dawley rats (n = 5) received heroin (10 mg kg −1) intraperitoneally, NLX (10 mg kg −1) intranasally, and NLX injected intranasally 5 min after heroin administration. The animals were sacrificed 15 min after dose and brain tissues were harvested. The MSI image analysis showed a region-specific distribution of 6-MAM in the brain regions including the corpus callosum, hippocampal formation, cerebral cortex, corticospinal tracts, caudate putamen, thalamus, globus pallidus, hypothalamus, and basal forebrain regions of the brain. The antagonist had a similar biodistribution throughout the brain in both groups of animals that received NLX or NLX after heroin administration. The MSI analysis demonstrated that the intensity of 6-MAM in these brain regions was reduced following NLX treatment. The decrease in 6-MAM intensity was caused by its displacement by the antagonist and its binding to these receptors in these specific brain regions, consequently enhancing the opioid elimination. These findings will contribute to the evaluation of other narcotic antagonists that might be considered for use in the treatment of drug overdose via MSI.

Journal of Molecular Histology

ASSAY and Drug Development Technologies

Rapid Communications in Mass Spectrometry

Journal of Molecular Histology

Journal of Psychiatric Research

RSC Advances

Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its local... more Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its localisation in the brain using mass spectrometry imaging (MSI). This study shows that BDQ has the potential for targeting TB reservoirs in the CNS.

Antibiotics

Virulent Enterobacterale strains expressing serine and metallo-β-lactamases (MBL) genes have emer... more Virulent Enterobacterale strains expressing serine and metallo-β-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop β-lactamase inhibitors to counter this resistance. Currently, serine β-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-β-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived β-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of ≤1 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 µM and 30.9 µM against New Delhi Metallo-β-lactamase (NDM-1) and ...

FEMS Microbiology Letters

The recent surge in beta-lactamase resistance has created superbugs, which pose a current and sig... more The recent surge in beta-lactamase resistance has created superbugs, which pose a current and significant threat to public healthcare. This has created an urgent need to keep pace with the discovery of inhibitors that can inactivate these beta-lactamase producers. In this study, the in vitro and in vivo activity of 1,4,7-triazacyclononane-1,4,7 triacetic acid (NOTA)—a potential metallo-beta-lactamase (MBL) inhibitor was evaluated in combination with meropenem against MBL producing bacteria. Time–kill studies showed that NOTA restored the efficacy of meropenem against all bacterial strains tested. A murine infection model was then used to study the in vivo pharmacokinetics and efficacy of this metal chelator. The coadministration of NOTA and meropenem (100 mg/kg.bw each) resulted in a significant decrease in the colony-forming units of Klebsiella pneumoniae NDM-1 over an 8-h treatment period (>3 log10 units). The findings suggest that chelators, such as NOTA, hold strong potential...

Nanofabrication

The purpose of this study was to synthesize duloxetine (DLX)- loaded Eudragit-Chitosan (Eud-CHT) ... more The purpose of this study was to synthesize duloxetine (DLX)- loaded Eudragit-Chitosan (Eud-CHT) nanoparticles enclosed in an oral gelatin capsule and to evaluate the potential to transport DLX to the blood-brain barrier (BBB)for improved neuro-availability. The utilization of Eudragit® with chitosan offers a pH-dependent controlled drug release. The physicochemical properties of the formulated DLX-loaded Eud-CHT nanosystem were confirmed using various characterization techniques. SEM confirmed the nanoparticle morphology and pore size distribution. The particle size was 100 ± 73,41 nm, with a polydispersity index (PDI) of 0,283 and zeta potential of 16±2,79 mV. Drug entrapment efficacy (DEE) of 72% was attained, and molecular modelling predicted an efficient and controllable drug delivery system. The release of DLX from the nanosystem was evaluated at pH1.2, pH 6.8 and pH 7.4. At a pH of 6.8, 40 % of DLX was released, with only 20 % at pH 1.2 and 35% at pH 7.4. This demonstrated DL...

South African Journal of Chemistry

The COVID-19 pandemic has resulted in an unprecedented surge in the demand for alcohol-based hand... more The COVID-19 pandemic has resulted in an unprecedented surge in the demand for alcohol-based hand sanitisers (ABHS). The Centre for Disease Control (CDC) and World Health Organisation (WHO) recommend alcohol, i.e., isopropanol or ethanol, at a 60-95% concentration in ABHS for sufficient antiviral protection. Consumers need to be vigilant of substandard hand sanitisers being marketed to the public. The frequent exposure of microorganisms to alcohol concentrations below the recommended range for infection prevention may lead to resistant mutations, and above the range may be ineffective. Therefore, this study aimed to verify the stated alcohol content in hand sanitisers from their respective labels. We analysed 50 hand sanitiser samples available to our region in Durban, KwaZulu-Natal, South Africa, using a Shimadzu GC-MS-QP2010 Ultra equipped with a Zebron ZB-wax capillary column. The hand sanitisers analysed had a range of 44-93% alcohol content. The data from our study also reveale...

Naicker for their invaluable inputs, initiatives and guidance. I learnt hard work, tenacity and h... more Naicker for their invaluable inputs, initiatives and guidance. I learnt hard work, tenacity and humility from you all. I especially appreciate Tricia for her uncommon understanding and her high level of emotional intelligence.

Pharmaceutics

As one of the most cutting-edge and promising polymer crosslinked network nanoparticle systems. P... more As one of the most cutting-edge and promising polymer crosslinked network nanoparticle systems. Polymer nano-sized hydrogels (nanogels) have been a hot topic in the biomedical field over the last few decades. Due to their unique characteristics, which include their relatively high drug encapsulation efficiency, ease of preparation, high tunability, low toxicity, high stability in serum and responsive behavior to a range of stimuli to facilitate drug release. Nanogels are thought to be the next generation of drug delivery systems that can completely change the way that drug delivery systems have an impact on patients’ lives. Nanogels have demonstrated significant potential in a variety of fields, including chemotherapy, diagnosis, organ targeting, and delivery of bioactive molecules of different dimensions. However, the lack of substantial clinical data from nanogels becomes one of the major barriers to translating the nanogel concept into a practical therapeutic application for many...

Biomedicines

High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of c... more High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of cancers in both adults and children. However, the toxicity associated with HDMTX has resulted in the spread of infections and treatment interruption. Further, poor bioavailability due to efflux pump activities mediated by P-glycoprotein has also been linked to poor therapeutic effects of methotrexate following oral administrations. D-α-Tocopheryl poly-ethylene glycol 1000 succinate (TPGS) is known to improve the bioavailability of poorly soluble drugs by inhibiting P-gp efflux activities, thus enhancing cellular uptake. Therefore, to achieve improved bioavailability for MTX, this study aimed to design and develop a novel drug delivery system employing TPGS and a biodegradable polymer, i.e., PLGA, to construct methotrexate-loaded nanoparticles fixated in alginate-gelatine 3D printable hydrogel ink to form a solid 3D printed tablet for oral delivery. The results indicated that high accuracy...

Polymers

Psoriasis vulgaris (PV) is a common chronic disease, affecting much of the population. Hydrocorti... more Psoriasis vulgaris (PV) is a common chronic disease, affecting much of the population. Hydrocortisone (HCT) is currently utilized as a PV treatment; however, it is associated with undesirable side effects. The aim of this research was to create a thermo-responsive nano-hydrogel delivery system. HCT-loaded sorbitan monostearate (SMS)-polycaprolactone (PCL) nanoparticles, encapsulated with thermo-responsive hydrogel carboxymethyl cellulose (CMC), were synthesized by applying the interfacial polymer-deposition method following solvent displacement. The nanoparticles’ properties were evaluated employing Differential Scanning Colorimetry, Thermogravimetric Analysis, Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Zeta sizer, Ultraviolet/Visual spectroscopy, and cytotoxicity testing. The nanoparticle sizes were 110.5 nm, with polydispersity index of 0.15 and zeta potential of −58.7 mV. A drug-entrapment efficacy of 76% was attained by the HCT-loaded SMS-PCL nanopart...

Polymers

In many clinical applications, the transdermal route is used as an alternative approach to avoid ... more In many clinical applications, the transdermal route is used as an alternative approach to avoid the significant limitations associated with oral drug delivery. There is a long history for drug delivery through the skin utilizing transdermal microneedle arrays. Microneedles are reported to be versatile and very efficient devices. This technique has spurred both industrial and scientific curiosity, due to its outstanding characteristics such as painless penetration, affordability, excellent medicinal efficiency, and relative protection. Microneedles possess outstanding properties for diverse biomedical uses such as the delivery of very large substances with ionic and hydrophilic physicochemical properties. Importantly, microneedles are applicable in numerous biomedical fields such as therapy, diagnosis, and vaccine administration. Microneedles are emerging tools that have shown profound potential for biomedical applications. Transdermal microneedle technologies are likely to become a...

ACS Omega

Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths... more Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths can be prevented through the timely administration of naloxone (NLX), a nonselective mu (μ)-, kappa (κ)-, and delta (δ)-opioid receptor antagonist. NLX competitively inhibits opioid-overdose-induced respiratory depression without eliciting any narcotic effect itself. The aim of this study was to investigate the antagonistic action of NLX by comparing its distribution to that of 6-monacetylmorphine (6-MAM), heroin's major metabolite, in a rodent model using mass spectrometric imaging (MSI) in combination with liquid chromatography−tandem mass spectrometry (LC−MS/MS). Male Sprague−Dawley rats (n = 5) received heroin (10 mg kg −1) intraperitoneally, NLX (10 mg kg −1) intranasally, and NLX injected intranasally 5 min after heroin administration. The animals were sacrificed 15 min after dose and brain tissues were harvested. The MSI image analysis showed a region-specific distribution of 6-MAM in the brain regions including the corpus callosum, hippocampal formation, cerebral cortex, corticospinal tracts, caudate putamen, thalamus, globus pallidus, hypothalamus, and basal forebrain regions of the brain. The antagonist had a similar biodistribution throughout the brain in both groups of animals that received NLX or NLX after heroin administration. The MSI analysis demonstrated that the intensity of 6-MAM in these brain regions was reduced following NLX treatment. The decrease in 6-MAM intensity was caused by its displacement by the antagonist and its binding to these receptors in these specific brain regions, consequently enhancing the opioid elimination. These findings will contribute to the evaluation of other narcotic antagonists that might be considered for use in the treatment of drug overdose via MSI.

Journal of Molecular Histology

ASSAY and Drug Development Technologies

Rapid Communications in Mass Spectrometry

Journal of Molecular Histology

Journal of Psychiatric Research

RSC Advances

Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its local... more Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its localisation in the brain using mass spectrometry imaging (MSI). This study shows that BDQ has the potential for targeting TB reservoirs in the CNS.