Intracellular delivery of nano-formulated antituberculosis drugs enhances bactericidal activity

Donnellan, Samantha; Stone, Vicki; Johnston, Helinor; Giardiello, Marco; Owen, Andrew; Rannard, Steve; Aljayyoussi, Ghaith; Swift, Benjamin; Tran, Lang; Watkins, Craig; Stevenson, Karen

Abstract

Tuberculosis kills more people worldwide than any other infectious disease. Treatment requires multiple drug therapy administered over long periods (6–24 months). The emergence of multidrug‐resistant strains is a major problem, and with few new drugs in the pipeline, a novel modus operandi is urgently required. Solid drug nanoparticles (SDNs), a new development in nanomedicine, offer a fresh therapeutic approach. Here, we show that SDNs are more effective (50‐fold) at killing pathogenic mycobacteria than aqueous forms of the same drug and can target mycobacteria internalised by macrophages, where bacilli reside. We demonstrate synthesis of dual and triple drug loaded SDNs, facilitating combination tuberculosis therapy. Our results suggest that by employing SDNs of existing antibiotics, it may be possible to improve drug delivery and therefore reduce drug dosage to lessen side effects and fight drug resistance.

Citation

Donnellan, S., Stone, V., Johnston, H., Giardiello, M., Owen, A., Rannard, S., Aljayyoussi, G., Swift, B., Tran, L., Watkins, C., & Stevenson, K. (2017). Intracellular delivery of nano-formulated antituberculosis drugs enhances bactericidal activity. Journal of Interdisciplinary Nanomedicine, 2(3), 146-156. https://doi.org/10.1002/jin2.27

• Journal Article Type: Article
• Acceptance Date: Aug 4, 2017
• Online Publication Date: Oct 2, 2017
• Publication Date: 2017-09
• Deposit Date: Feb 11, 2021
• Publicly Available Date: Feb 11, 2021
• Journal: Journal of Interdisciplinary Nanomedicine
• Print ISSN: 2058-3273
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 2
• Issue: 3
• Pages: 146-156
• DOI: https://doi.org/10.1002/jin2.27
• Keywords: Mycobacteria, nanomedicine, solid drug nanoparticles, tuberculosis
• Public URL: http://researchrepository.napier.ac.uk/Output/2718395