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Inhalable porous pa...
Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis
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- Campos Pacheco, Jesús Enrique (author)
- Malmö University,Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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- Yalovenko, Tetiana (author)
- Malmö University,Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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- Riaz, Azra (author)
- Malmö University,Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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- Kotov, Nikolay (author)
- KTH Royal Institute of Technology,KTH,Yt- och korrosionsvetenskap,Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden
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- Davids, Camilla (author)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Medicinsk mikrobiologi,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Medical Microbiology,Lund University Research Groups
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- Persson, Alva (author)
- Malmö University,Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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- Falkman, Peter (author)
- Malmö University,Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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- Feiler, Adam (author)
- KTH Royal Institute of Technology,KTH,Yt- och korrosionsvetenskap,Nanologica AB (publ), Forskargatan 20G, 151 36 Södertälje, Sweden, Forskargatan 20G
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- Godaly, Gabriela (author)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Medicinsk mikrobiologi,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Medical Microbiology,Lund University Research Groups
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- Johnson, Magnus (author)
- KTH Royal Institute of Technology,KTH,Yt- och korrosionsvetenskap,Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden
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- Ekström, Mikael (author)
- Iconovo AB, Ideongatan 3A-B, 223 70 Lund, Sweden, Ideongatan 3A-B
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- Pilkington, Georgia (author)
- KTH Royal Institute of Technology,KTH,Yt- och korrosionsvetenskap,Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden; Nanologica AB (publ), Forskargatan 20G, 151 36 Södertälje, Sweden
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- Valetti, Sabrina (author)
- Malmö University,Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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(creator_code:org_t)
- Elsevier B.V. 2024
- 2024
- English.
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In: Journal of Controlled Release. - : Elsevier B.V.. - 0168-3659 .- 1873-4995. ; 369, s. 231-250
- Related links:
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https://doi.org/10.1...
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https://mau.diva-por... (primary) (Raw object)
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Inhalation therapy treating severe infectious disease is among the more complex and emerging topics in controlled drug release. Micron-sized carriers are needed to deposit drugs into the lower airways, while nano-sized carriers are of preference for cell targeting. Here, we present a novel and versatile strategy using micron-sized spherical particles with an excellent aerodynamic profile that dissolve in the lung fluid to ultimately generate nanoparticles enabling to enhance both extra- and intra-cellular drug delivery (i.e., dual micro-nano inhalation strategy). The spherical particles are synthesised through the condensation of nano-sized amorphous silicon dioxide resulting in high surface area, disordered mesoporous silica particles (MSPs) with monodispersed size of 2.43 μm. Clofazimine (CLZ), a drug shown to be effective against multidrug-resistant tuberculosis, was encapsulated in the MSPs obtaining a dry powder formulation with high respirable fraction (F.P.F. <5 μm of 50%) without the need of additional excipients. DSC, XRPD, and Nitrogen adsorption-desorption indicate that the drug was fully amorphous when confined in the nano-sized pores (9–10 nm) of the MSPs (shelf-life of 20 months at 4 °C). Once deposited in the lung, the CLZ-MSPs exhibited a dual action. Firstly, the nanoconfinement within the MSPs enabled a drastic dissolution enhancement of CLZ in simulated lung fluid (i.e., 16-fold higher than the free drug), increasing mycobacterial killing than CLZ alone (p = 0.0262) and reaching concentrations above the minimum bactericidal concentration (MBC) against biofilms of M. tuberculosis (i.e., targeting extracellular bacteria). The released CLZ permeated but was highly retained in a Calu-3 respiratory epithelium model, suggesting a high local drug concentration within the lung tissue minimizing risk for systemic side effects. Secondly, the micron-sized drug carriers spontaneously dissolve in simulated lung fluid into nano-sized drug carriers (shown by Nano-FTIR), delivering high CLZ cargo inside macrophages and drastically decreasing the mycobacterial burden inside macrophages (i.e., targeting intracellular bacteria). Safety studies showed neither measurable toxicity on macrophages nor Calu-3 cells, nor impaired epithelial integrity. The dissolved MSPs also did not show haemolytic effect on human erythrocytes. In a nutshell, this study presents a low-cost, stable and non-invasive dried powder formulation based on a dual micro-nano carrier to efficiently deliver drug to the lungs overcoming technological and practical challenges for global healthcare.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Clofazimine
- Disordered mesoporous silica particles
- Dissolution enhancement
- Dried powder formulation
- Dual micro-nano carrier
- Lung drug delivery
- Soluble carrier
- Clofazimine
- Disordered mesoporous silica particles
- Dissolution enhancement
- Dried powder formulation
- Dual micro-nano carrier
- Lung drug delivery
- Soluble carrier
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Campos Pacheco, ...
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Yalovenko, Tetia ...
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Riaz, Azra
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Kotov, Nikolay
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Davids, Camilla
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Persson, Alva
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show more...
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Falkman, Peter
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Feiler, Adam
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Godaly, Gabriela
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Johnson, Magnus
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Ekström, Mikael
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Pilkington, Geor ...
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Valetti, Sabrina
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
- Articles in the publication
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Journal of Contr ...
- By the university
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Royal Institute of Technology
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Malmö University
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Lund University