Clofazimine encapsulation in nanoporous silica particles for the oral treatment of antibiotic-resistant Mycobacterium tuberculosis infections.
First extensive reformulation of clofazimine (CLZ) in nanoporous silica particles (NSPs) for tackling antibiotic-resistant tuberculosis (TB) infections.



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.



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.



Promising results toward refurbishment of an approved marketed drug for a different indication suitable for oral anti-TB formulation.
Nanologica AB, SE-151 36 Södertälje, Sweden.|Biofilms - Research Center for Biointerfaces, Department of Biomedical Sciences, Faculty of Health & Sciences, Malmö University, Sweden.
Sabrina
S
Valetti
Nanologica AB, SE-151 36 Södertälje, Sweden.
Xin
X
Xia
Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur deLille, U1019 - UMR 8204 - CIIL - Center for Infection & Immunity of Lille, F-59000 Lille, France.
Joana
J
Costa-Gouveia
Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur deLille, U1019 - UMR 8204 - CIIL - Center for Infection & Immunity of Lille, F-59000 Lille, France.
Priscille
P
Brodin
EA4043 Unité BactériesPathogènes et Santé (UBaPS), Univ. Paris-Sud, Université Paris-Saclay, 92296, Châtenay-Malabry Cedex, France.
Marie-Françoise
MF
Bernet-Camard
Nanologica AB, SE-151 36 Södertälje, Sweden.
Margareta
M
Andersson
Nanologica AB, SE-151 36 Södertälje, Sweden.|Surface and Corrosion Science, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
Adam
A
Feiler
D000284:Administration, Oral; D018938:Caco-2 Cells; D002991:Clofazimine / Q000008:administration & dosage* / Q000737:chemistry; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000472:pathogenicity; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D058608:Nanopores; D010539:Permeability / Q000187:drug effects; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D012822:Silicon Dioxide; D002991:Clofazimine
Caco-2 cells; HPLC; amorphous; clofazimine; drug carrier; intramacrophage in vitro assay; nanoporous silica particles; oral drug delivery; tuberculosis