Browsing by Author "Van Rensburg, Lyne"
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- ItemAntimycobacterial agents : a study of Liposomal-Encapsulation, comparitive permeability of bronchial tissue and in vitro activity against mycobacterium tuberculosis isolates(Stellenbosch : Stellenbosch University, 2012-12) Van Rensburg, Lyne; Van Zyl, J. M.; Seifart, H. I.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. Pharmacology.ENGLISH ABSTRACT: In this thesis, research results are reported on the role of dipalmitoyl phosphatidyl choline (DPPC) and DPPC-liposomes on the in vitro permeability characteristics of various antimycobacterial drugs across porcine bronchial tissue. The permeability flux values of the different compounds (isoniazid, ofloxacin and moxifloxacin) and their relevant DPPC formulations were determined using a continuous flow through perfusion system. Mean steady state flux values were compared statistically by means of a t-test at a significance level of 5% as well as an F-test using whole curve comparisons. The results indicated that the different formulations of drug and their DPPC combinations retard the permeation of drug through bronchial tissue. However, moxifloxacin permeation was significantly enhanced when in a DPPC-liposomal formulation. These results demonstrate the important role that molecular weight, electrostatic charge, partitioning of the molecules in DPPC and DPPC-liposomes play in transmembrane diffusion. In addition, the effect of individual drugs and their DPPC combinations on the surface tension lowering property of DPPC was evaluated. The results obtained showed minimal decreases in the surface tension lowering capability of DPPC; however, the minimal increases in surface tension do not alter the integrity of DPPC to a large extent. Drug susceptibility testing of Mycobacterium tuberculosis cultures against the individual antitubercular drugs and their DPPC combinations was done by using the Radiometric BACTEC 460TB™ system. Drug-entrapped DPPC liposomes were tested at concentrations comparable to their relative minimum inhibitory concentrations (MIC). The results for the BACTEC assay indicated that the mycobacteria were susceptible to the developed drug entrapped liposomes; of which their encapsulation efficiencies for the relevant drugs were approximately ± 50%. It was concluded that drug-entrapped DPPC liposomes could fulfill the dual role of pulmonary drug delivery and alveolar stabilization due to antiatelectatic effect of DPPC which can improve the distribution of anti-tubercular drugs in the lung
- ItemDeposition and transport of linezolid mediated by a synthetic surfactant Synsurf® within a pressurized metered dose inhaler : a Calu-3 model(Dove Medical Press, 2018) Van Rensburg, Lyne; Van Zyl, Johann M.; Smith, JohanBackground: Previous studies in our laboratory demonstrated that a synthetic peptide containing lung surfactant enhances the permeability of chemical compounds through bronchial epithelium. The purpose of this study was to test two formulations of Synsurf® combined with linezolid as respirable compounds using a pressurized metered dose inhaler (pMDI). Methods: Aerosolization efficiency of the surfactant-drug microparticles onto Calu-3 monolayers as an air interface culture was analyzed using a Next Generation Impactor™. Results: The delivered particles and drug dose showed a high dependency from the preparation that was aerosolized. Scanning electron microscopy imaging allowed for visualization of the deposited particles, establishing them as liposomal-type structures (diameter 500 nm to 2 µm) with filamentous features. Conclusion: The different surfactant drug combinations allow for an evaluation of the significance of the experimental model system, as well as assessment of the formulations providing a possible noninvasive, site-specific, delivery model via pMDI.
- ItemEffect of exogenous surfactant on Paediatric Bronchoalveolar lavage derived macrophages’ cytokine secretion(BMC (part of Springer Nature), 2019-12-05) Van Rensburg, Lyne; Van Zyl, Johann M,; Smith, Johan; Goussard, PierreBackground: Bronchoalveolar lavage is a useful bronchoscopy technique. However, studies in “normal” children populations are few. Furthermore, the anti-inflammatory effects of exogenous pulmonary surfactants on the bronchoalveolar cellular components are limited. Methods: Thirty children, aged 3 to 14 years, underwent diagnostic bronchoscopy and bronchoalveolar lavage. Differential cytology, cytokine and chemokine measurements were performed on the fluid after exogenous surfactant exposure. The aim of the study was to investigate the potential anti-inflammatory effects of exogenous surfactants on the bronchoalveolar lavage fluid, specifically alveolar macrophages of healthy South African children. Results: Alveolar macrophages were the predominant cellular population in normal children. Patients with inflammatory pneumonopathies had significantly more neutrophils. Levels of inflammatory cytokines were significantly lower after exogenous surfactant exposure. Moreover, IL-10 and IL-12 cytokine secretion increased after exogenous surfactant exposure. Conclusion: This study provides the first data on bronchoalveolar lavage of healthy South African children. Bronchoalveolar lavage fluid from patients with pulmonary inflammation was characterised by neutrophilia. Finally, we propose that exogenous surfactant treatment could help alleviate inflammation in diseased states where it occurs in the tracheobronchial tree.
- ItemImmunoactive, Antibacterial and Drug-Carrying properties of selective surfactants(Stellenbosch : Stellenbosch University, 2018-03) Van Rensburg, Lyne; Van Zyl, Johann Martin; Smith, Johan; Van Zyl, Johann Martin; Smith, Johan; Stellenbosch University. Faculty of medicine of Health Sciences. Dept. Medicine: Clinical Pharmacology.ENGLISH ABSTRACT: Surfactant replacement therapy is used the treatment of neonatal respiratory distress syndrome as surfactant’s biophysical behaviour helps to maintain proper lung function and reduces the work associated with breathing. Secondly, surfactant associated proteins are important role players in the innate immune response within the pulmonary environment and therefore assist in pulmonary host defence. However, natural and synthetic exogenous surfactants have gained much interest in other areas of therapy such as possibly aiding in dual-drug delivery systems for infectious or inflammatory pulmonary conditions. Both types have been studied extensively in animal models and in clinical trials and have elicited positive and negative effects on lung function. This thesis aims to determine whether a synthetic peptide containing surfactant, Synsurf®, may have potential immunomodulatory effects compared to the naturally derived surfactants, Curosurf® and Liposurf®. Two formulations of Synsurf®, combined with the antibiotic linezolid were tested for its efficacy as a respirable compound in a pressurised metered dose inhaler. The outcome of these experiments revealed the prospect of Synsurf®’s adaptability as a pulmonary drug carrier. Furthermore, the tuberculosis isolates H37Rv and MDR-X51 displayed enhanced susceptibility to surfactant-drug micro-particle combinations. The main findings of this study show that the natural surfactants Curosurf® and Liposurf® as well as Synsurf® inhibit secretion of pro-inflammatory cytokines and influence the production of reactive oxygen species in NR8383 alveolar macrophages and therefore influence cell viability. The inhibitory effects on cytokine secretion was displayed in a dose-dependent manner as well as a threshold effect that was seen for all three surfactants. This may result from unique mechanisms of decreasing cell signalling or up-regulating anti-inflammatory activity that was further elucidated by the employment of proteomics. The findings in this thesis on the comparison of the two natural and one synthetic surfactant led to the following main conclusions: a) Different surfactant compositions modulate the anti-inflammatory activity in lipopolysaccharide stimulated alveolar macrophages via the possible involvement of different signalling pathways. The initial hypothesis regarding the protective nature that is linked to the protein content in natural surfactants is challenged and may be deemed as “not fully supported” as these new findings suggest non-specific lipid or synthetic peptide protection with alveolar macrophages as seen with Synsurf®. b) Different surfactant compositions effect cell viability and morphology in a time and dose-dependent manner revealing that the treatment of neonatal respiratory distress syndrome may depend upon the specific preparation or dose used. c) All three surfactants displayed an impact on the antibiotic activity of linezolid that holds positive ramifications for drug loaded surfactants. d) The data shows that linezolid in combination with Synsurf® can be aerosolised in desired particle ranges for optimal lung deposition for a possible non-invasive, site-specific, delivery model via pressurised metered dose inhaler.