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Spray-Dried, Nanoencapsulated, Multi-Drug Anti-Tuberculosis Therapy Aimed at Once Weekly Administration for the Duration of Treatment

1
Council for Scientific and Industrial Research, Pretoria 0002, South Africa
2
Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria 0002, South Africa
*
Author to whom correspondence should be addressed.
Nanomaterials 2019, 9(8), 1167; https://doi.org/10.3390/nano9081167
Received: 27 June 2019 / Revised: 21 July 2019 / Accepted: 28 July 2019 / Published: 15 August 2019
(This article belongs to the Special Issue Applications of Nano-Designed Systems in Biomedical Research)
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Abstract

Aiming 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 efficiencies 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 efficacy 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. View Full-Text
Keywords: nanomedicine; tuberculosis; spray-drying technology; efficacy; dose frequency nanomedicine; tuberculosis; spray-drying technology; efficacy; dose frequency
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Kalombo, L.; Lemmer, Y.; Semete-Makokotlela, B.; Ramalapa, B.; Nkuna, P.; Booysen, L.L.; Naidoo, S.; Hayeshi, R.; Verschoor, J.A.; Swai, H.S. Spray-Dried, Nanoencapsulated, Multi-Drug Anti-Tuberculosis Therapy Aimed at Once Weekly Administration for the Duration of Treatment. Nanomaterials 2019, 9, 1167.

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