Malmö University Publications
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  • 1.
    Campos Pacheco, Jesus Enrique
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Riaz, Azra
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Feiler, Adam
    Nanolog AB publ, Södertälje, Sweden.;KTH Royal Inst Technol, Surface & Corros Sci, Stockholm, Sweden..
    Ekström, Mikael
    Iconovo AB, Lund, Sweden..
    Pilkington, Georgia
    Nanolog AB publ, Södertälje, Sweden..
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Encapsulation of clofazimine in mesoporous silica as a potential dry powder formulation for treating tuberculosis2023In: Journal of Aerosol Medicine, ISSN 1941-2711, E-ISSN 1941-2703, Vol. 36, no 6, p. A13-A13, article id A13Article in journal (Other academic)
  • 2.
    Campos Pacheco, Jesús Enrique
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Yalovenko, Tetiana
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Riaz, Azra
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kotov, Nikolay
    Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
    Davids, Camilla
    Department of Microbiology, Immunology and Glycobiology, Institution of Laboratory Medicine, Lund University, Lund, Sweden.
    Persson, Alva
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Feiler, Adam
    Godaly, Gabriela
    Department of Microbiology, Immunology and Glycobiology, Institution of Laboratory Medicine, Lund University, Lund, Sweden.
    Johnson, C Magnus
    Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
    Ekström, Mikael
    Iconovo AB, Ideongatan 3A-B, 223 70 Lund, Sweden.
    Pilkington, Georgia A
    Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden; Nanologica AB (publ), Forskargatan 20G, 151 36 Södertälje, Sweden.
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis2024In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 369, p. 231-250, article id S0168-3659(24)00165-2Article in journal (Refereed)
    Abstract [en]

    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.

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  • 3.
    Hernandez, Aura Rocio
    et al.
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Bogdanova, Ekaterina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Campos Pacheco, Jesus Enrique
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Feiler, Adam
    Nanolog AB, Södertälje, Sweden..
    Pilkington, Georgia
    Nanolog AB, Södertälje, Sweden..
    Ekström, Mikael
    Iconovo AB, Lund, Sweden..
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Disordered mesoporous silica particles as emerging platform to deliver biologic molecules to the lungs2023In: Journal of Aerosol Medicine, ISSN 1941-2711, E-ISSN 1941-2703, Vol. 36, no 6, article id A32Article in journal (Other academic)
  • 4.
    Yalovenko, Tetiana
    et al.
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Campos Pacheco, Jesus Enrique
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Schousboe, Emilie
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Gustafsson, Anna
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Pilkington, Georgia
    Nanologica AB, Södertälje, Sweden..
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Cell viability and inflammatory responses of amorphous mesoporous silica particles on different macrophage cells2023In: Journal of Aerosol Medicine, ISSN 1941-2711, E-ISSN 1941-2703, Vol. 36, no 6, p. A37-A38Article in journal (Other academic)
1 - 4 of 4
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