Browsing by Author "Semete-Makokotlela, Boitumelo"
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Item In vivo/in vitro pharmacokinetic and pharmacodynamic study of spray-dried poly-(dl-lactic-co-glycolic) acid nanoparticles encapsulating rifampicin and isoniazid.(Elsevier B.V., 2013-02-28) Booysen, Laetitia; Kalombo, Lonji; Brooks, Elizabeth; Hansen, Ryan; Gilliland, Janet; Gruppo, Veronica; Lungenhofer, Paul; Semete-Makokotlela, Boitumelo; Swai, Hulda; Kotzé, Awie; Lenaerts, Anne; du Plessis, LissindaPoly-(dl-lactic-co-glycolic) acid (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation spray-drying technique and coated with polyethylene glycol (PEG 1% v/v). The PLGA nanoparticles had a small size (229±7.6 to 382±23.9nm), uniform size distribution and positive zeta potential (+12.45±4.53mV). In vitro/in vivo assays were performed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) performance of these nanoparticles following nanoencapsulation of the anti-tuberculosis drugs rifampicin (RIF) and isoniazid (INH). The results demonstrated the potential for the reduction in protein binding of these drugs by protection in the polymer core. Furthermore, in vitro efficacy was demonstrated using Mycobacterium tuberculosis (M. tb.) (strain H37Rv). Sustained drug release over seven days were observed for these drugs following once-off oral administration in mice with subsequent drug distribution of up to 10 days in the liver and lungs for RIF and INH, respectively. It was concluded by these studies combined with our previous reports that spray-dried PLGA nanoparticles demonstrate potential for the improvement of tuberculosis chemotherapy by nanoencapsulation of anti-tuberculosis drugs.Item Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis(Elsevier, 2015-06-06) Lemmer, Yolandy; Kalombo, Lonji; Pietersen, Ray-Dean; Jones, Arwyn T.; Semete-Makokotlela, Boitumelo; Van Wyngaardt, Sandra; Ramalapa, Bathabile; Stoltz, Anton C.; Baker, Bienyameen; Verschoor, Jan A.; Swai, Hulda; de Chastellier, ChantalThe 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 nanotechnologiesmight 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 cellwallmycolic acids (MA) as targeting ligands into a drug-encapsulating Poly DL-lactic-co-glycolic acid polymer (PLGA), via a double emulsion solvent evaporation technique. Bonemarrow-derivedmousemacrophages, either uninfected or infectedwith differentmycobacterial 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) nanoparticlecontaining phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed.Item Spray-Dried, Nanoencapsulated, Multi-Drug Anti-Tuberculosis Therapy Aimed at OnceWeekly Administration for the Duration of Treatment(MDPI, 2019-08-15) Kalombo, Lonji; Lemmer, Yolandy; Semete-Makokotlela, Boitumelo; Ramalapa, Bathabile; Nkuna, Patric; Booysen, Laetitia; Naidoo, Saloshnee; Hayeshi, Rose; Verschoor, Jan; Swai, HuldaAiming to improve the treatment outcomes of current daily tuberculosis (TB) chemotherapy over several months, we investigated whether nanoencapsulation of existing drugs would allow decreasing the treatment frequency to weekly, thereby ultimately improving patient compliance. Nanoencapsulation of three first-line anti-TB drugs was achieved by a unique, scalable spray-drying technology forming free-flowing powders in the nanometer range with encapsulation e ciencies of 82, 75, and 62% respectively for rifampicin, pyrazinamide, and isoniazid. In a pre-clinical study on TB infected mice, we demonstrate that the encapsulated drugs, administered once weekly for nine weeks, showed comparable e cacy to daily treatment with free drugs over the same experimental period. Both treatment approaches had equivalent outcomes for resolution of inflammation associated with the infection of lungs and spleens. These results demonstrate how scalable technology could be used to manufacture nanoencapsulated drugs. The formulations may be used to reduce the oral dose frequency from daily to once weekly in order to treat uncomplicated TB.