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Clofazimine encapsulation in nanoporous silica particles for the oral treatment of antibiotic-resistant Mycobacterium tuberculosis infections
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2017 (English)In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 12, no 8, 831-844 p.Article in journal (Refereed) Published
Abstract [en]

Aim: First extensive reformulation of clofazimine (CLZ) in nanoporous silica particles (NSPs) for tackling antibiotic-resistant tuberculosis (TB) infections. Materials & methods: Solid-state characterization of several CLZ-encapsulated NSP formulations was followed by in vitro drug solubility, Caco-2 intestinal cells drug permeability and TB antibacterial activity. Results: NSPs stabilize the amorphous state of CLZ (shelf stability > 6 months) and dramatically increase the drug solubility in simulated gastric fluid (up to 20-fold) with different dissolution kinetics depending on the NSPs used. CLZ encapsulation in NSP substantially enhances the permeation through model intestinal cell layer, achieving effective antimicrobial concentrations in TB-infected macrophages. Conclusion: Promising results toward refurbishment of an approved marketed drug for a different indication suitable for oral anti-TB formulation.

Place, publisher, year, edition, pages
FUTURE MEDICINE LTD , 2017. Vol. 12, no 8, 831-844 p.
Keyword [en]
amorphous, Caco-2 cells, clofazimine, drug carrier, HPLC, intramacrophage in vitro assay, nanoporous silica particles, oral drug delivery, tuberculosis
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-206697DOI: 10.2217/nnm-2016-0364ISI: 000398957600003PubMedID: 28338408ScopusID: 2-s2.0-85017365568OAI: oai:DiVA.org:kth-206697DiVA: diva2:1094031
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QC 20170509

Available from: 2017-05-09 Created: 2017-05-09 Last updated: 2017-05-09Bibliographically approved

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