Sabrina Valetti1,2, Xin Xia1, Joana Costa-Gouveia3, Priscille Brodin3, Marie-Françoise Bernet-Camard4, Margareta Andersson1, Adam Feiler1,5. 1. Nanologica AB, SE-151 36 Södertälje, Sweden. 2. Biofilms - Research Center for Biointerfaces, Department of Biomedical Sciences, Faculty of Health & Sciences, Malmö University, Sweden. 3. Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur deLille, U1019 - UMR 8204 - CIIL - Center for Infection & Immunity of Lille, F-59000 Lille, France. 4. EA4043 Unité BactériesPathogènes et Santé (UBaPS), Univ. Paris-Sud, Université Paris-Saclay, 92296, Châtenay-Malabry Cedex, France. 5. Surface and Corrosion Science, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
Abstract
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.
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.
Entities:
Keywords:
Caco-2 cells; HPLC; amorphous; clofazimine; drug carrier; intramacrophage in vitro assay; nanoporous silica particles; oral drug delivery; tuberculosis
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