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Antitubercular Nanocarrier Combination Therapy: Formulation Strategies and in Vitro Efficacy for Rifampicin and SQ641

Author(s): D'Addio, Suzanne M.; Reddy, Venkata M.; Liu, Ying; Sinko, Patrick J.; Einck, Leo; et al

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dc.contributor.authorD'Addio, Suzanne M.-
dc.contributor.authorReddy, Venkata M.-
dc.contributor.authorLiu, Ying-
dc.contributor.authorSinko, Patrick J.-
dc.contributor.authorEinck, Leo-
dc.contributor.authorPrudhomme, Robert K.-
dc.date.accessioned2020-01-31T19:40:50Z-
dc.date.available2020-01-31T19:40:50Z-
dc.date.issued2015-03-26en_US
dc.identifier.citationD'Addio, SM, Reddy, VM, Liu, Y, Sinko, PJ, Einck, L, Prud'homme, RK. (2015). Antitubercular nanocarrier combination therapy: Formulation strategies and in vitro efficacy for rifampicin and SQ641. Molecular Pharmaceutics, 12 (1554 - 1563). doi:10.1021/mp5008663en_US
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/pr11n3h-
dc.description.abstractTuberculosis (TB) remains a major global health concern, and new therapies are needed to overcome the problems associated with dosing frequency, patient compliance, and drug resistance. To reduce side effects associated with systemic drug distribution and improve drug concentration at the target site, stable therapeutic nanocarriers (NCs) were prepared and evaluated for efficacy in vitro in Mycobacterium tuberculosis-infected macrophages. Rifampicin (RIF), a current, broad-spectrum antibiotic used in TB therapy, was conjugated by degradable ester bonds to form hydrophobic prodrugs. NCs encapsulating various ratios of nonconjugated RIF and the prodrugs showed the potential ability to rapidly deliver and knockdown intracellular M. tuberculosis by nonconjugated RIF and to obtain sustained release of RIF by hydrolysis of the RIF prodrug. NCs of the novel antibiotic SQ641 and a combination NC with cyclosporine A were formed by flash nanoprecipitation. Delivery of SQ641 in NC form resulted in significantly improved activity compared to that of the free drug against intracellular M. tuberculosis. A NC formulation with a three-compound combination of SQ641, cyclosporine A, and vitamin E inhibited intracellular replication of M. tuberculosis significantly better than SQ641 alone or isoniazid, a current first-line anti-TB drug.en_US
dc.format.extent1554 - 1563en_US
dc.language.isoen_USen_US
dc.relation.ispartofMolecular Pharmaceuticsen_US
dc.rightsFinal published version. This is an open access article.en_US
dc.titleAntitubercular Nanocarrier Combination Therapy: Formulation Strategies and in Vitro Efficacy for Rifampicin and SQ641en_US
dc.typeJournal Articleen_US
dc.identifier.doidoi:10.1021/mp5008663-
pu.type.symplectichttp://www.symplectic.co.uk/publications/atom-terms/1.0/journal-articleen_US

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