ResearchSpace :: Browsing by Author "Lemmer, Yolandy"

Browsing by Author "Lemmer, Yolandy"

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The antigenicity and cholesteroid nature of mycolic acids determined by recombinant chicken antibodies
(PLOS, 2018-08) Ranchod, Heena; Ndlandla, Fortunate L; Lemmer, Yolandy; Beukes, M; Niebuhr, J; Al-Dulayymi, J
Mycolic acids (MA) are major, species-specific lipid components of Mycobacteria and related genera. In Mycobacterium tuberculosis, it is made up of alpha-, methoxy- and keto-MA, each with specific biological functions and conformational characteristics. Antibodies in tuberculosis (TB) patient sera respond differently towards the three MA classes and were reported to cross-react with cholesterol. To understand the antigenicity and cholesterol cross-reactivity of MA, we generated three different chicken-derived phage-displayed single-chain variable fragments (scFv) that reacted similarly towards the natural mixture of MA, but the first recognized all three classes of chemically synthetic MAs, the second only the two oxygenated types of MAs and the third only methoxy MA. The cholesterol cross-reactivity was investigated after grafting each of the three scFv types onto two configurations of constant chain domains±CH1-4 and CH2-4. Weak but significant cross-reactivity with cholesterol was found only with CH2-4 versions, notably those two that were also able to recognize the trans-keto MA. The cholesteroid nature of mycobacterial mycolic acids therefore seems to be determined by the trans-keto MA subclass. The significantly weaker binding to cholesterol in comparison to MA confirms the potential TB diagnostic application of these antibodies.
Application of monoclonal anti-mycolate antibodies in serological diagnosis of tuberculosis
(2024-11) Truyts, Alma E; Du Preez, Ilse; Maesela, Maushe E; Scriba, Manfred R; Baillie, L; Jones, AT; Land, KJ; Verschoor, JA; Lemmer, Yolandy
Patient loss to follow-up caused by centralised and expensive diagnostics that are reliant on sputum is a major obstacle in the fight to end tuberculosis. An affordable, non-sputum biomarker-based, point-of-care deployable test is needed to address this. Serum antibodies binding the mycobacterial cell wall lipids, mycolic acids, have shown promise as biomarkers for active tuberculosis. However, anti-lipid antibodies are of low affinity, making them difficult to detect in a lateral flow immunoassay—a technology widely deployed at the point-of-care. Previously, recombinant monoclonal anti-mycolate antibodies were developed and applied to characterise the antigenicity of mycolic acid. We now demonstrate that these anti-mycolate antibodies specifically detect hexane extracts of mycobacteria. Secondary antibody-mediated detection was applied to detect the displacement of the monoclonal mycolate antibodies by the anti-mycolic acid antibodies present in tuberculosis-positive guinea pig and human serum samples. These data establish proof-of-concept for a novel lateral flow immunoassay for tuberculosis provisionally named MALIA—mycolate antibody lateral flow immunoassay.
Bionanopolymers for drug delivery
(Springer, 2019-07) Fasiku, VO; Owonubi, SJ; Mukwevho, E; Aderibigbe, B; Sadiku, E; Lemmer, Yolandy; Reddy, AB; Manjula, B; Nkuna, C; Dludlu, MK
In medicine, the need and demand for the successful delivery of pharmacologically active materials or therapeutic compounds to cells, tissues, and organs in the system have made drug delivery techniques broadly studied. Several drug delivery methods have been developed and investigated in the past. The aim is to design better approaches to treat various diseases affecting humans in the world. This has led to the development and use of different materials of natural and synthetic origin as drug delivery devices. However, certain limitations and challenges have been faced with the use of most of these materials hence the need for more suitable alternatives. Some of these limitations include material toxicity, non-biocompatibility, and nonflexibility among others. At the moment, research has brought to limelight some group of materials with unique properties that can potentially serve as drug delivery systems. They are commonly referred to as biopolymers and because they can be manipulated, they can be fabricated into nanosizes (sizes of between 1 and 100 nm); hence, they are called bionanopolymers. Bionanopolymers are generally of natural origin, they are biodegradable and biocompatible. These properties have made them widely employed in biomedical applications. Bionanopolymers have gained attention in drug delivery and have contributed to the progress recorded in the treatment of disease conditions such as cancer, diabetes, allergy, infection, and inflammation.
Blood ketone bodies and breath acetone analysis and their correlations in Type 2 Diabetes Mellitus
(MDPI AG, 2019-12) Saasa, Valentine; Beukes, M; Lemmer, Yolandy; Mwakikunga, Bonex W
Analysis of volatile organic compounds in the breath for disease detection and monitoring has gained momentum and clinical significance due to its rapid test results and non-invasiveness, especially for diabetes mellitus (DM). Studies have suggested that breath gases, including acetone, may be related to simultaneous blood glucose (BG) and blood ketone levels in adults with types 2 and 1 diabetes. Detecting altered concentrations of ketones in the breath, blood and urine may be crucial for the diagnosis and monitoring of diabetes mellitus. This study assesses the efficacy of a simple breath test as a non-invasive means of diabetes monitoring in adults with type 2 diabetes mellitus. Human breath samples were collected in Tedlar™ bags and analyzed by headspace solid-phase microextraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS). The measurements were compared with capillary BG and blood ketone levels (ß-hydroxybutyrate and acetoacetate) taken at the same time on a single visit to a routine hospital clinic in 30 subjects with type 2 diabetes and 28 control volunteers. Ketone bodies of diabetic subjects showed a significant increase when compared to the control subjects; however, the ketone levels were was controlled in both diabetic and non-diabetic volunteers. Worthy of note, a statistically significant relationship was found between breath acetone and blood acetoacetate (R = 0.89) and between breath acetone and ß-hydroxybutyrate (R = 0.82).
Carboxy-PEG-thiol functionalized gold nanoparticle conjugates for the detection of SARS-CoV-2: Detection tools and analytical method development
(2024-12) Hlekelele, Lerato; Setshedi, Katlego Z; Mandiwana, Vusani; Kalombo, Lonji; Lemmer, Yolandy; Chauke, Chauke P; Maity, Arjun
Addressing the need for accessible SARS-CoV-2 testing, carboxy-PEG 12-thiol functionalized gold nanoparticles conjugates were developed for rapid point-of-care (POC) detection against SARS-CoV-2 spike protein, pseudo-SARS-CoV-2, and authentic Beta SARS-CoV-2 virus particles. These conjugates leverage gold nanoparticles (AuNPs) as signal transducers, cross-linked to either angiotensin-converting enzyme 2 (ACE2) or SARS-CoV-2 spike protein receptor-binding domain (RBD) antibodies as bioreceptors and showed a distinct color shift from pink to blue. To assess their POC feasibility, the conjugates were integrated into facemasks and breathalyzers, wherein aerosolized SARS-CoV-2 antigens were successfully detected, producing a color change within 10 and 30 minutes for the breathalyzer and facemask prototypes, respectively. Furthermore, we explored quantitative analysis using varying concentrations of SARS-CoV-2 spike protein. Both conjugates demonstrated a linear relationship between blue color intensity and virus concentration, with linear ranges of 0.08–0.6 ng/mL and 0.04–0.5 ng/mL, respectively. Low limits of detection and quantification were also achieved. They exhibited specificity, responding solely to SARS-CoV-2 even in complex matrices containing diverse proteins, including the SARS-CoV-1 spike protein. Precision tests yielded coefficient of variations below 2 %, showcasing their remarkable reproducibility. This work presents a promising approach for rapid, sensitive, and specific POC detection of SARS-CoV-2 paving the way for improved pandemic response and management.
Detection of antimycolic acid antibodies by liposomal biosensors
(Elsevier, 2009) Lemmer, Yolandy; Thanyani, ST; Vrey, PJ; Driver, CHS; Venter, L; Van Wyngaardt, S; Ten Bokum, AMC; Ozoemena, KI; Pilcher, LA; Fernig, DG; Stoltz, AC; Swai, HS; Verschoor, JA
Antibodies to mycolic acid (MA) antigens can be detected as surrogate markers of active tuberculosis (TB) with evanescent field biosensors where the lipid antigens are encapsulated in liposomes. Standard immunoassay such as ELISA, where the lipid antigen is not encapsulated, but directly adsorbed to the wellbottoms of microtiter plates, does not yield the required sensitivity and specificity for accurate diagnosis of TB. One reason for this is the cross-reactivity of natural anticholesterol antibodies with MAs. MAs are the major cell wall lipids of mycobacteria. Mycobacterial MA has immunomodulatory properties and elicits specific antibodies in TB patients. Liposomes were optimized for their use as carriers both for the presentation of immobilized purified mycobacterial MA on sensor surfaces, and as a soluble inhibitor of antibody binding in inhibition assays. By using an inhibition assay in the biosensor, the interference by anticholesterol antibodies is reduced. Here, we describe the MA carrying capacity of liposomes with and without cholesterol as a stabilizing agent, optimized concentration and size of liposomes for use in the biosensor assay, comparison of the methods for wave-guide and surface plasmon resonance biosensors and how the cholesteroid nature of MA can be demonstrated by the biosensor when Amphotericin B is allowed to bind to MA in liposomes.
Effect of varying ethanol and water compositions on the acetone sensing properties of WO3 for application in diabetes mellitus monitoring
(IOP Publishing Ltd, 2020-03) Saasa, Valentine; Lemmer, Yolandy; Malwela, Thomas; Akande, Amos A; Beukes, M; Mwakikunga, Bonex W
Tungsten oxide based gas sensors have attracted a lot of attention in breath acetone analysis due to their potential in clinical diagnosis of diabetes. The major problem with this material in sensor application has been remarkable response to all gases but low selectivity to specific gases. Herein, we report the gas sensing performance of WO3 materials which were synthesized by varying water and ethanol ratios using a facile solvothermal method for acetone detection. The gas sensing properties of as-prepared WO3 were tested on acetone C7H8, NO2, NH3, H2S and CH4 under relative humidity. X-ray diffraction patterns show that as-prepared WO3 samples are mainly composed of monoclinic WO3, a phase having relatively high selectivity to acetone. The as-prepared WO3 sensors produced using 51:49 ratio of water: ethanol show an increase in acetone response as the acetone concentration increases and a decrease in acetone response as the relative humidity increases. The sensor responded to a very low acetone concentration ranging from 0.5 to 4.5 ppm which is normally found in human breath. Furthermore, the sensor exhibited high sensitivity and selectivity to low ppm of acetone at 100 °C. On contrary, the sensor showed significantly lower response to other gases tested.
Graphene-based materials for implants
(Wiley, 2019-06) Fasiku, F; Owonubi, S; Mukwevho, E; Aderibigbe, B; Sadiku, E; Lemmer, Yolandy
Over the years, many different materials, e.g., titanium (Ti) and its alloys, have been used in biomedicine for several purposes. A common application of such materials is seen in their usage as implants. However, quite a number of graphene-based materials have emerged and developed from a two dimensional single atomic thick block of a carbon allotrope, known as graphene. Since the discovery and isolation of graphene from graphite in the year 2004, there has been tremendous positive improvement in health conditions which require treatments that involves the use of implants. World-wide, this has led to significant attention and appreciation of this versatile material, in biomedicine and obviously, in all fields of science and engineering. Examples of some of the graphene-based materials to be discussed, include: reduced graphene oxide (rGO) and graphite oxide (GO). Although, graphene-based materials are distinguishable by their individual and unique properties, nevertheless, they still have certain characteristics in common. Owing to these properties, possessed by different graphene-based materials, they are able to serve in the biomedical field as implants in order to combat a wide range of diseases that have been a challenge, previously. This chapter elaborates on some different graphenebased materials, in respect to their: structures, synthesis, properties, advantages and disadvantages and the applications of these materials as implants in biomedicine.
The hierarchical nanostructured Co-doped WO3/carbon and their improved acetone sensing performance
(2020-10) Saasa, Valentine R; Malwela, Thomas; Lemmer, Yolandy; Beukes, M; Mwakikunga, Bonex W
Hierarchical nanostructured Co-doped WO3 with carbon as template has been successfully synthesised through facile sol-gel method. The synthesised Co-doped WO3 was characterized by X-ray diffraction, Scanning electron microscopy, Transmission electron microscopy, Energy dispersive X-ray spectrometry, and Brunauer-Emmett-Teller and X-ray photoelectron spectroscopy. The gas sensing properties of WO3 doped with Co from 0 to 0.8 wt % were also investigated on various VOCs. The fabricated sensor based on 0.6 wt% Co-doped WO3 with carbon as a template showed good sensitivity, selectivity, fast response and recovery time towards 1.5 ppm of acetone at 50 °C under 90% relative humidity. The excellent gas sensing properties could be attributed to high surface area, small crystallite size, defect of WO3 and Co catalysis effect which promotes gas adsorption and most importantly the stabilized monoclinic phase of WO3, which accounts for the good selectivity.
Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/-mice
(2024-04) O’Kennedy, Martha M; Roth, Robyn; Ebersohn, K; Du Plessis, LH; Mamputha, Sipho; Rutkowska, Daria A; Du Preez, Ilse; Verschoor, JA; Lemmer, Yolandy
A safe, highly immunogenic multivalent vaccine to protect against all nine serotypes of African horse sickness virus (AHSV), will revolutionise the AHS vaccine industry in endemic countries and beyond. Plant-produced AHS virus-like particles (VLPs) and soluble viral protein 2 (VP2) vaccine candidates were developed that have the potential to protect against all nine serotypes but can equally well be formulated as mono- and bi-valent formulations for localised outbreaks of specific serotypes. In the first interferon a/ß receptor knock-out (IFNAR-/-) mice trial conducted, a nine-serotype (nonavalent) vaccine administered as two pentavalent (5 µg per serotype) vaccines (VLP/VP2 combination or exclusively VP2), were directly compared to the commercially available AHS live attenuated vaccine. In a follow up trial, mice were vaccinated with an adjuvanted nine-serotype multivalent VP2 vaccine in a prime boost strategy and resulted in the desired neutralising antibody titres of 1:320, previously demonstrated to confer protective immunity in IFNAR-/- mice. In addition, the plant-produced VP2 vaccine performed favourably when compared to the commercial vaccine. Here we provide compelling data for a nonavalent VP2-based vaccine candidate, with the VP2 from each serotype being antigenically distinguishable based on LC-MS/MS and ELISA data. This is the first preclinical trial demonstrating the ability of an adjuvanted nonavalent cocktail of soluble, plant-expressed AHS VP2 proteins administered in a prime-boost strategy eliciting high antibody titres against all 9 AHSV serotypes. Furthermore, elevated T helper cells 2 (Th2) and Th1, indicative of humoral and cell-mediated memory T cell immune responses, respectively, were detected in mouse serum collected 14 days after the multivalent prime-boost vaccination. Both Th2 and Th1 may play a role to confer protective immunity. These preclinical immunogenicity studies paved the way to test the safety and protective efficacy of the plant-produced nonavalent VP2 vaccine candidate in the target animals, horses.
In vivo evaluation of the biodistribution and safety of PLGA nanoparticles as drug delivery systems
(Elsevier, 2010-10) Semete, B; Booysen, L; Lemmer, Yolandy; Kalombo, Lonji; Katata, L; Verschoor, J; Swai, HS
The remarkable physicochemical properties of particles in the nanometer range have been proven to address many challenges in the field of science. However, the possible toxic effects of these particles have raised some concerns. The aim of this article is to evaluate the effects of poly(lactide-co-glycolide) (PLGA) nanoparticles in vitro and in vivo compared to industrial nanoparticles of a similar size range such as zinc oxide, ferrous oxide, and fumed silica. An in vitro cytotoxicity study was conducted to assess the cell viability following exposure to PLGA nanoparticles. Viability was determined by means of a WST assay, wherein cell viability of greater than 75% was observed for both PLGA and amorphous fumed silica particles and ferrous oxide, but was significantly reduced for zinc oxide particles. In vivo toxicity assays were performed via histopathological evaluation, and no specific anatomical pathological changes or tissue damage was observed in the tissues of Balb/C mice. The extent of tissue distribution and retention following oral administration of PLGA particles was analyzed for 7 days. After 7 days, the particles remained detectable in the brain, heart, kidney, liver, lungs, and spleen. The results show that a mean percentage (40.04%) of the particles was localized in the liver, 25.97% in the kidney, and 12.86% in the brain. The lowest percentage was observed in the spleen. Thus, based on these assays, it can be concluded that the toxic effects observed with various industrial nanoparticles will not be observed with particles made of synthetic polymers such as PLGA when applied in the field of nanomedicine. Furthermore, the biodistribution of the particles warrants surface modification of the particles to avoid higher particle localization in the liver.
Lipid containing nanodrug delivery system for the treatment of Tuberculosis
(CSIR, 2010-09-01) Lemmer, Yolandy; Semete, B; Kalombo, Lonji; Ramalapa, B; Jones, AT; Swai, HS; Verschoor, JA
Challenges in treatment of Tuberculosis (TB) include non-specific localisation of the drugs which results in too low concentrations of the drugs reaching the target site of infection, thus leading to reduced effectiveness. To improve the current inadequate therapeutic management of TB, a polymeric nanodrug delivery system, for anti-TB drugs was developed by a double emulsion evaporation technique. The system could enable entry, targeting, sustained release for longer periods and uptake of the antibiotics in the cells, hence reducing the dose frequency and simultaneously improve patient compliance. The cell wall envelope of Mycobacterium tuberculosis (M.tb) contains unique high molecular weight lipids. Of these, the most abundant are mycolic acids (MA), an extended family of long 2-alkyl 3-hydroxyl fatty acids, typically 70-90 carbon atoms in length, with peculiar physical and biological properties. MA have further been shown to have a similarity in the structural properties with cholesterol1. MA were explored as the targeting agent to infected macrophages containing abundance of cholesterol.
Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis
(Elsevier, 2015-06) Lemmer, Yolandy; Kalombo, Lonji; Pietersen, R-D; Jones, AT; Semete-Makokotlela, Boitumelo; Van Wyngaardt, S; Ramalapa, BE; Stoltz, A; Baker, B; Verschoor, JA; Swai, HS; De Chastellier, C
The appearance of drug-resistant strains of Mycobacterium tuberculosis (Mtb) poses a great challenge to the development of novel treatment programmes to combat tuberculosis. Since innovative nanotechnologies might alleviate the limitations of current therapies, we have designed a new nanoformulation for use as an anti-TB drug delivery system. It consists of incorporating mycobacterial cellwall mycolic acids (MA) as targeting ligands into a drug-encapsulating Poly DL-lactic-co-glycolic acid polymer (PLGA), via a double emulsion solvent evaporation technique. Bone marrow-derived mouse macrophages, either uninfected or infected with different mycobacterial strains (Mycobacterium avium, Mycobacterium bovis BCG or Mtb), were exposed to encapsulated isoniazid-PLGA nanoparticles (NPs) using MA as a targeting ligand. The fate of the NPs was monitored by electron microscopy. Our study showed that i) the inclusion of MA in the nanoformulations resulted in their expression on the outer surface and a significant increase in phagocytic uptake of the NPs; ii) nanoparticle-containing phagosomes were rapidly processed into phagolysosomes, whether MA had been included or not; and iii) nanoparticle-containing phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed.
Nanomedicine in the development of drugs for poverty-related diseases
(Springer-Verlag, 2012) Hayeshi, R; Semete, B; Kalombo, Lonji; Katata, L; Lemmer, Yolandy; Melariri, P; Nyamboli, B; Swai, H
Nanotechnology is a multidisciplinary field covering the design, manipulation, characterisation, production and application of structures, devices and systems at nanometer scale (1–500-nm-size range) which, at this size range, presents with unique or superior physicochemical properties. This scale represents the size of atoms, molecules and macromolecules. Nanomedicine is the application of nanotechnology in medical sciences for imaging, diagnosis, drug delivery (nanocarriers) and therapeutics used for treating and preventing disease.
A narrative review of the therapeutic and remedial prospects of cannabidiol with emphasis on neurological and neuropsychiatric disorders
(2024-03) Omotayo, OP; Lemmer, Yolandy; Mason, S
The treatment of diverse diseases using plant-derived products is actively encouraged. In the past few years, cannabidiol (CBD) has emerged as a potent cannabis-derived drug capable of managing various debilitating neurological infections, diseases, and their associated complications. CBD has demonstrated anti-inflammatory and curative effects in neuropathological conditions, and it exhibits therapeutic, apoptotic, anxiolytic, and neuroprotective properties. However, more information on the reactions and ability of CBD to alleviate brain-related disorders and the neuroinflammation that accompanies them is needed.
Polyhydroxyalkanoates (PHAs) as scaffolds for tissue engineering
(New York: Nova Science Publishers, 2018-05) Sadiku, ER; Fasiku, VO; Owonubi, SJ; Mukwevho, E; Aderibigbe, BA; Lemmer, Yolandy; Abbavaram, BR; Manjula, B; Nkuna, C; Dludlu, MK
Tissue engineering is a filed that has gained a lot of advancement since the discovery of biopolymers. Biopolymers are polymers produced by living organisms: that is, they are polymeric biomolecules. They consist of monomeric units that ar covalently bonded to one another in order to form larger structures. Biopolymers have been widely used as biomaterials for the construction of tissue engineering scaffold. Scaffolds have been used for tissue engineering, such as: bone, cartilage, ligament, skin, vascular tissues, neural tissues, and skeletal muscles. Polyhydroxyester is a typical example of biopolymers that have been employed for this application. Their exceptional properties such as high surface-to-volume ratio, high porosity with vwery small pore size, biodegradation, and mechanical property have made them gain a lot of attention in this field. Also, they have advantages which are significant for tissue engineering. This chapter will focus on the production, modification, properties and medical applications of polyhydroxyesters, such as PLA (Polylactide), PGA (Polyglycolide or poly(glycolic acid), PCL (Polycaprolactone), poly(ester amide)s and PLGA (Poly(lactide-co-glycolide), with particular emphasis on the different plyhydroxyalkanoates (PHAs), which have divrse applicatioins in tissue engineering.
Polyhydroxyesters as scaffolds for tissue engineering
(Nova Science Publishers, 2018-05) Fasiku, VO; Owonubi, SJ; Mukwevho, E; Aderibigber, BA; Sadiku, ER; Agboola, O; Lemmer, Yolandy; Kupolati, WK; Selatile, K; Makgatho, G
Tissue engineering is a field that has gained a lot of advancement since the discovery of biopolymers. Biopolymers are simply polymers that are made-up of polymeric biomolecules. They consist of monomeric units that are covalently bonded to one another in order to form very large structures. Biopolymers have been widely used as biomaterials for the construction of tissue scaffold. Scaffolds have been used for tissue engineering such as bone, cartilage, ligament, skin, vascular tissues, neutral tissues and skeletal muscles. Polyhydroxyesters are typical examples of synthetic biopolymers that have been employed for this application. Their exceptional properties, such as: high surface-to-volume ratio, high porosity with very small pore size, biodegrading, and mechanical property have made them gain a lot of attention in this field. Also, they have advantages which are significant for tissue engineering. This chapter focuses on polyhydroxeester, such as: PLA (Polylactide), PGA (Polyglycolide0, which have diverse applications in tissue engineering. Details of these polyhydroxyesters and their application in tissue engineering will be discussed in this chapter.
Polylactide-based magnetic spheres as efficient carriers for anticancer drug delivery
(ACS Publications, 2015-09) Mhlanga, N; Ray, Suprakas S; Lemmer, Yolandy; Wesley-Smith, J
To improve traditional cancer therapies, we synthesized polylactide (PLA) spheres coencapsulating magnetic nanoparticles (MNPs, Fe(sub3)O(sub4)) and an anticancer drug (doxorubicin, DOX). The synthesis process involves the preparation of Fe(sub3)O(sub4) NPs by a coprecipitation method and then PLA/DOX/Fe(sub3)O(sub4) spheres using the solvent evaporation (oil-in-water) technique. The Fe(sub3)O(sub4) NPs were coated with oleic acid to improve their hydrophobicity and biocompatibility for medical applications. The structure, morphology and properties of the MNPs and PLA/DOX/Fe(sub3)O(sub4) spheres were studied using various techniques, such as FTIR, SEM, TEM, TGA, VSM, UV-vis spectroscopy, and zeta potential measurements. The in vitro DOX release from the spheres was prolonged, sustained, and pH-dependent and fit a zero-order kinetics model and an anomalous mechanism. Interestingly, the spheres did not show a DOX burst effect, ensuring the minimal exposure of the healthy cells and an increased drug payload at the tumor site. The pronounced biocompatibility of the PLA/DOX/Fe(sub3)O(sub4) spheres with HeLa cells was proven by a WST assay. In summary, the synthesized PLA/DOX/Fe(sub3)O(sub4) spheres have the potential for magnetic targeting of tumor cells to transform conventional methods.
Potential of improving the treatment of tuberculosis through nanomedicine
(Taylor & Francis, 2012-03) Semete, B; Kalombo, Lonji; Katata, L; Chelule, P; Booysen, L; Lemmer, Yolandy; Naidoo, Saloshnee; Ramalapa, B; Hayeshi, R; Swai, HS
Current treatment of tuberculosis is inadequate due to lengthy treatment course and drug-related toxicity. To address these setbacks, we developed a nanotechnology drug delivery system that can be administered in a single dose that maintains an active level of drug for at least a week. Polymeric poly(lactic-co-glycolic acid) nanoparticles of 200–300 nm were synthesized, with a drug encapsulation efficiency of 50–65% for isoniazid and rifampicin. The particles were taken up in vitro and in vivo and a slow release profile was observed in mice over 5 days. This study illustrates the feasibility of a sustained release system for tuberculosis treatment.
Preclinical assessment of 68Ga-PSMA-617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging
(Wiley, 2019-06) Mandiwana, Vusani; Kalombo, Lonji; Lemmer, Yolandy; Labuschagne, Philip W; Semete-Makokotlela, Boitumelo; Sathekge, M; Ebenhan, T; Rijn Zeevaart, J
It has in recent years been reported that microemulsion (ME) delivery systems provide an opportunity to improve the efficacy of a therapeutic agent whilst minimising side effects and also offer the advantage of favourable treatment regimens. The prostate-specific membrane antigen (PSMA) targeting agents PSMA-11 and PSMA-617, which accumulate in prostate tumours, allow for [68 Ga]Ga3+ -radiolabelling and positron emission tomography/computed tomography (PET) imaging of PSMA expression in vivo. We herein report the formulation of [68 Ga]Ga-PSMA-617 into a ME ≤40 nm including its evaluation for improved cellular toxicity and in vivo biodistribution. The [68 Ga]Ga-PSMA-617-ME was tested in vitro for its cytotoxicity to HEK293 and PC3 cells. [68 Ga]Ga-PSMA-617-ME was administered intravenously in BALB/c mice followed by microPET/computed tomography (CT) imaging and ex vivo biodistribution determination. [68 Ga]Ga-PSMA-617-ME indicated negligible cellular toxicity at different concentrations. A statistically higher tolerance towards the [68 Ga]Ga-PSMA-617-ME occurred at 0.125 mg/mL by HEK293 cells compared with PC3 cells. The biodistribution in wild-type BALB/C mice showed the highest amounts of radioactivity (%ID/g) presented in the kidneys (31%) followed by the small intestine (10%) and stomach (9%); the lowest uptake was seen in the brain (0.5%). The incorporation of [68 Ga]Ga-PSMA-617 into ME was successfully demonstrated and resulted in a stable nontoxic formulation as evaluated by in vitro and in vivo means.

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