Browsing by Author "Mocktar, Chunderika."

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Antimicrobial and chemical analyses of selected bulbine species.
(2000) Mocktar, Chunderika.; Essack, Sabiha Yusuf.; Rogers, B. C.; Dangor, Cassim Mahomed.
The use of plant materials for the treatment of various diseases is very common in African countries. As traditional medicine used by the rural people does not always have a proper scientific basis, research programmes have to be undertaken to evaluate their therapeutic efficacy and safety. In traditional African medicine various Bulbine species are used to treat a number of conditions including sexually transmitted diseases, wound infections, dysentery and urinary tract infections. The Bulbine species belong to the family Asphodelaceae. There are over fifty South African Bulbine species and they are mostly herbs. Their leaves are evergreen and succulent in appearance. Bulbine species have thick fleshy tuberous roots, are easy to grow, are able to withstand drought and heat and are able to grow in poor soil. There is very little documented information on the antimicrobial activity and chemical properties of the Bulbine species. Therefore research programmes of this nature have to be undertaken. Various Bulbine species, viz., B. natalensis Bak, B. frutescens Willd (yellow flowers), B. narcissifalia Salm Dyck, B. abyssinica A Rich and B. frutescens Willd (orange flowers) were collected. The plants were washed with tap water, air dried and separated into the different components. Each component was cut into small pieces and immersed in methanol: dichloromethane (1:1, v/v) for extraction. The organic solvent was decanted from the plant material and evaporated under reduced pressure. The resultant crude extracts were stored in glass vials in the freezer. In addition, the roots, stems and leaves of B. natalensis and B. frutescens (yellow flowers) were extracted aqueously. The crude organic and aqueous were subjected to various tests to evaluate their antimicrobial and cytotoxic potential. To evaluate their antibacterial activities, the Disk Diffusion and Bore Well Methods were employed. The crude extracts were tested against various pathogens implicated in wound and urinary tract infections and dysentery. In these experiments the Disk Diffusion Method produced better results than the Bore Well Method. The crude organic and aqueous extracts were found to be effective against many of the bacteria used in this study including K. pneumoniae, S. aureus, S. typhi and S. flexneri which are considered to be troublesome pathogens. The TLC bioassay was employed to evaluate the antifungal potential of the various crude extracts against Aspergillus and Penicillium and the Disk Diffusion and Bore Well methods were used to evaluate the antifungal potential of C. albicans. The Bulbine species displayed no antifungal activity against Penicillium and limited antifungal activity against Aspergillus. The two method used to evaluate the antifungal activity of. C albicans was chosen because C. albicans grows in a similar manner to bacteria on solid and liquid culture media. Only the root extracts of the two B. frutescens varieties were inhibitory to C. albicans. The Brine Shrimp Bioassay was used to ascertain the cytotoxic potential of the crude extracts. The majority of the extracts were cytotoxic at the most concentrated dilution (i.e., dilution 1) but not cytotoxic at the lower dilutions. The only extracts that were not cytotoxic at the most concentrated dilution were the organic extract of the root of B. frutescens (yellow flowers), the organic extract of the root of B. narcissifolia and the organic extract of the leaf of B. abyssinica. TLC and column chromatography was carried out to evaluate the chemical composition of the Bulbine species. The TLC indicate that this technique could be a valuable tool in identifying the different species in the genus Bulbine. Column chromatogram was carried out on the extract which displayed a significant amount of antibacterial activity against the bacteria used in this study. The stem extract of B. natalensis was chosen for further analysis. The stem extract was fractitioned into different fractions but unfortunately none of the chemical component could be identified. According to the results obtained in this study, there is considerable scope for further studies of this genus.
Beta-lactamase mediated resistance in Escherichia Coli isolated from state hospitals in KwaZulu-Natal.
(2008) Mocktar, Chunderika.; Essack, Sabiha Yusuf.; Sturm, Adriaan Willem.
Escherichia coli, one of the most common pathogens causing urinary tract infections, has shown increased resistance to commonly used antibiotics. In this study we analyzed the β-lactamase profiles of 38 inhibitor-resistant E. coli isolates obtained from public hospitals at three different levels of healthcare in KwaZulu-Natal, selected on the basis of their resistance profiles to the three antibiotic/inhibitor combinations, viz., amoxicillin/clavulanate, ampicillin/ sulbactam and piperacillin/ tazobactam. The isolates were subjected to MIC determinations, IEF analysis, plasmid profile analysis, PCR of the different β-lactamase genes and sequencing thereof to detect the possible mechanism/s of resistance. A range of β-lactamases including two novel inhibitor-resistant TEM β-lactamases, TEM-145 and TEM-146 were detected in two isolates whilst a novel plasmid-mediated AmpC-type β-lactamase, CMY-20 was detected in three isolates. Other β-lactamases included OXA-1, TEM-55, SHV-2, CTX-M-l and TEM-1. Changes were detected in the chromosomal AmpC promoter/attenuator regions in one isolate. Diverse β-lactamase genes and plasmid profiles inferred extensive mobilization of β-lactamase genes causing the concern of limited therapeutic options in the face of increasing resistance.
Design of advanced materials and nano delivery approaches for enhancing activity against Methicillin resistant Staphylococcus aureus.
(2018) Omolo, Calvin Andeve.; Govender, Thirumala.; Mocktar, Chunderika.
Infectious diseases, including bacterial infections, continue to be a significant cause of morbidity and mortality globally, antimicrobial resistance has further made them fatal. Limitations of conventional dosage forms have been found to be one of the contributing factors to antimicrobial resistance. Novel nano delivery systems are showing potential to combat antimicrobial resistance. The search for novel materials for efficient delivery of antibiotics is an active research area. The aim of the study was to design and synthesize advanced materials and explore nano-based strategies for preparations of novel drug delivery systems to treat SA and MRSA infections. In this study two novel materials; a linear polymer dendrimer hybrid star polymer (3-mPEA) comprising of a generation one poly (ester-amine) dendrimer (G1-PEA) and copolymer of methoxy poly (ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL) and oleic acid based quaternary lipid (QL) were synthesized and characterized and Poloxamer 188 (P188) material available in the market were employed to formulate three nano drug delivery systems for efficient and targeted delivery of antibiotics. The synthesized materials and the drug delivery system were found to be biosafe after exhibiting cell viability above 75% in all the cell lines tested on using MTT assay. The formulated nano based systems were evaluated for sizes, polydispersity indices (PDI), zeta potential (ZP), surface morphology, drug release, in vitro and in vivo antibacterial activity. Nanovesicles were formulated from 3-mPEA and they had sizes, PDI, ZP and entrapment efficiency of 52.48 ± 2.6 nm, 0.103 ± 0.047, -7.3 ± 1.3 mV and 76.49 ± 2.4%. respectively. QL lipid was employed to formulate vancomycin (VCM) loaded liposomes with Oleic acid based ‘On’ and ‘Off’” pH responsive switches for infection site and intracellular bacteria targeting. They were found to have the size of 98.88 ± 01.92 at pH 7.4. and exhibited surface charge switching from negative at pH 7.4 to positive charge accompanied by faster drug release at pH 6.0. Fusidic acid nanosuspension (FA-NS) with size, PDI and ZP of 265 ± 2.25 nm, 0.158 ± 0.026 and -16.9 ± 0.794 mV respectively was formulated from P188. The drug release profile from both the nanovesicles and liposomes was found to have sustained release. In vitro antibacterial activity for the nanovesicles, FA-NS and liposomes showed 8, 6 and 4-fold better activity at pH 7.4, while the liposome being a pH responsive antibacterial system at pH 6 showed 8- and 16- fold better activity against both Methicillin susceptible (MSSA) and resistant Staphylococcus aureus (MRSA) respectively when compared with the bare drugs. An in vivo BALB/c mice, skin infection model revealed that treatment with VCM-loaded nanovesicles, liposomes and FA-Ns significantly reduced the MRSA burden compared to bare drugs and untreated groups. There was a 20, 6.33 and 76-fold reduction in the MRSA load in mice skin treated with nanovesicles, liposomes and FA-NS respectively compared to those treated with bare VCM and fusidic acid. In summary, synthesized material showed to be biosafe and potential for the development of nano-based drug delivery systems of antibiotics against bacterial infections. The data from this study has resulted in one book chapter and 3 first authored and 3 co-authored research publications.
Formulation and evaluation of novel vancomycin loaded lipidpolymer hybrid nanoparticles for effective antibiotic therapy.
(2015) Seedat, Nasreen.; Govender, Thirumala.; Mocktar, Chunderika.
Abstract available in PDF file.
Nanotherapeutics to combat infections.
(2019) Walvekar, Pavan.; Govender, Thirumala.; Mocktar, Chunderika.
The rise of drug resistant microorganisms is threatening the ability of antimicrobials to treat infectious diseases including bacterial infections, thus becoming a significant cause for premature mortality. Limitations associated with conventional dosage forms are one of the contributing factors for increasing antimicrobial resistance. Novel nano-drug delivery systems are showing considerable potential to combat antimicrobial resistance. The application of advanced novel materials for the efficient delivery of antibiotics is an active research area. The aim of the study was to design and synthesize advanced materials, and explore nano-based strategies for preparations of novel drug-delivery systems to treat MRSA infections. In this study, two sets of novel amphiphiles; fatty acid based pyridinium cationic amphiphiles (FCAs) and novel hyaluronic acid-oleylamine (HA-OLA) conjugates were synthesized and characterized. The synthesized novel amphiphiles were employed to formulate two nano-drug delivery systems for efficient delivery of vancomycin (VCM) to treat S. aureus and MRSA infections. The synthesized materials were found to have inherent antibacterial activity on tested bacterial strains and proven to be biosafe after exhibiting cell viability above 75% on all tested mammalian cell lines using MTT assay. The formulated nano-systems were characterized in terms of particle sizes, polydispersity indices (PDI), zeta potential (ZP), surface morphology, in vitro and in vivo (VCM loaded OCA vesicles) antibacterial activity. Oleic based cationic amphiphile (OCA) was employed to construct VCM loaded OCA vesicles, and had sizes, PDI, ZP and entrapment efficiency of 132.9 ± 2.5 nm, 0.167 ± 0.02, 18.9 ± 1.2 mV and 61.24 ± 1.8%, respectively. VCM loaded polymersomes prepared using HA-OLA6 had sizes, PDI, ZP and entrapment efficiency of 248.7 ± 3.08 nm, 0.189 ± 0.01, -17.6 ± 0.6 mV and. 43.12 ± 2.18%, respectively. The drug release from VCM loaded OCA vesicles and VCM loaded HA-OLA polymersomes (VCM-PS6) was sustained throughout the studied period of 72 h. From in vitro antibacterial studies, both FCAs and HA-OLA conjugates showed bactericidal activity against the tested bacterial strains. Both VCM loaded OCA vesicles and VCM-PS6 displayed 4-fold enhanced antibacterial activity against MRSA, when compared to bare VCM. Furthermore, synergism was observed between VCM and synthesized novel amphiphiles (FCAs and HA-OLA conjugates) in nano-formulations against MRSA. An in vivo BALB/c mice skin infection model revealed that, treatment with VCM loaded OCA vesicles significantly reduced the MRSA burden compared to bare drugs and untreated groups. There was 4.2-fold reduction in the MRSA load in mice skin treated with VCM loaded OCA vesicles compared to those treated with bare VCM. In summary, synthesized novel materials showed good biosafety, antibacterial activity and drug delivery potential via nano-systems against bacterial infections. The data from this study has resulted in one first authored review article, two first authored and one co-authored research publications.
Synthesis of novel polymeric materials for antimicrobial applications.
(2015) Suleman, Nadia.; Govender, Thirumala.; Mocktar, Chunderika.
Abstract available in PDF file.