Browsing by Author "Van Zyl, Johann M."
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- 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.
- ItemThe effect of certain N-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on moloney murine leukaemia virus reverse transcriptase activity(Academy of Science of South Africa (ASSAf), 2010-07) Van Zyl, Johann M.; Ariatti, Mario; Hawtrey, Arthur O.Moloney murine leukaemia virus M-MuLV) is a member of the retrovirus family. Its cloned reverse transcriptase RT), similarly to HIV type 1 reverse transcriptase HIV-1 RT), exhibits DNA-polymerase and ribonuclease H RNase H) activities capable of converting the single-stranded retroviral RNA genome into double-stranded DNA. The latter is then integrated into the host chromosome during viral infection. M-MuLV RT is, therefore, an attractive enzyme to help understand mutations in HIV-1 RT and its use in inhibition studies can help facilitate new drug designs. In this study, conjugates consisting of N-trityl derivatives of p-fluoro, p-nitro and p-iodo-DL-phenylalanine were coupled to 8-6-aminohexyl) amino-adenosine-3',5'-cyclic monophosphate and examined for their effect on DNA synthesis by M-MuLV RT. Synthesis was studied in a system containing poly rA).oligo dpT)15 as a template-primer with [ 3H] dTTP. The iodo-derivative, N-trityl-p-iodo-DL-phenylalanine-8-6- aminohexyl) amino-adenosine-3',5'-cyclic monophosphate was found to be a very active inhibitor of the RT enzyme IC50 = 1 μM), while the p-nitro IC50 = 45 μM) and p-fluoro IC50 = 65 μM) were weak inhibitors. Further work will be aimed at determining the mode of binding of the N-tritylated conjugates and also of various substituted amino acids and short peptides to M-MuLV RT to elucidate the mechanisms of inhibition. © 2010. The Authors.