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Disordered mesoporous silica particles: an emerging platform to deliver proteins to the lungs
Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.ORCID iD: 0000-0003-2233-1436
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.ORCID iD: 0009-0000-9729-0574
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.ORCID iD: 0000-0002-9852-5440
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2024 (English)In: Drug Delivery, ISSN 1071-7544, E-ISSN 1521-0464, Vol. 31, no 1, article id 2381340Article in journal (Refereed) Published
Abstract [en]

Pulmonary delivery and formulation of biologics are among the more complex and growing scientific topics in drug delivery. We herein developed a dry powder formulation using disordered mesoporous silica particles (MSP) as the sole excipient and lysozyme, the most abundant antimicrobial proteins in the airways, as model protein. The MSP had the optimal size for lung deposition (2.43 ± 0.13 µm). A maximum lysozyme loading capacity (0.35 mg/mg) was achieved in 150 mM PBS, which was seven times greater than that in water. After washing and freeze-drying, we obtained a dry powder consisting of spherical, non-aggregated particles, free from residual buffer, or unabsorbed lysozyme. The presence of lysozyme was confirmed by TGA and FT-IR, while N2 adsorption/desorption and SAXS analysis indicate that the protein is confined within the internal mesoporous structure. The dry powder exhibited excellent aerodynamic performance (fine particle fraction <5 µm of 70.32%). Lysozyme was released in simulated lung fluid in a sustained kinetics and maintaining high enzymatic activity (71–91%), whereas LYS-MSP were shown to degrade into aggregated nanoparticulate microstructures, reaching almost complete dissolution (93%) within 24 h. MSPs were nontoxic to in vitro lung epithelium. The study demonstrates disordered MSP as viable carriers to successfully deliver protein to the lungs, with high deposition and retained activity.

Place, publisher, year, edition, pages
Taylor & Francis, 2024. Vol. 31, no 1, article id 2381340
Keywords [en]
Dried powder inhalation, mesoporous silica particles, micronised drug carrier, protein formulation, pulmonary drug delivery
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:mau:diva-70063DOI: 10.1080/10717544.2024.2381340ISI: 001275373400001PubMedID: 39041383Scopus ID: 2-s2.0-85199320256OAI: oai:DiVA.org:mau-70063DiVA, id: diva2:1886645
Available from: 2024-08-02 Created: 2024-08-02 Last updated: 2025-04-17Bibliographically approved
In thesis
1. Inhalable bioinspired porous carrier as sole excipient in dry powder formulation for treating lung infections
Open this publication in new window or tab >>Inhalable bioinspired porous carrier as sole excipient in dry powder formulation for treating lung infections
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pulmonary drug delivery is a well-suited approach for treating lung infections, providing direct and targeted treatment to infected cells. This method enhances drug concentration in the lungs while reducing the required dosage. However, the physiological characteristics of the lungs constitute a complex barrier to drug delivery. Conventional methods often underperform or fail completely, particularly with poorly soluble drugs and inhaled proteins. This thesis explores the use of mesoporous silica particles (MSPs) as sole excipient in dry powder formulations to improve the treatment of lung infections. This study investigated the use of micron-sized mesoporous silica particles (MSPs) as a drug vehicle for clofazimine (CLZ) to target the lung. In simulated lung fluid (SLF), CLZ was released from the MSPs and subsequently formed nanoparticles. This micro-nano strategy significantly enhanced both extracellular and intracellular bactericidal efficacy in relation to mycobacteria, demonstrating its potential for multidrug-resistant TB. This formulation ensured high local drug retention and minimal side effects, indicating that lower CLZ doses could be administered relative to current oral treatment while sustaining adequate antimicrobial concentrations in the lungs. A second study demonstrated the use of MSPs in formulating proteins, specifically lysozyme (LYS), as a dry powder inhaler (DPI), while also examining aerosolization and release profiles. The observed protein lung deposition and preserved enzymatic activity post-release underscored the versatility of MSPs in this therapeutic application. The toxicological effects of MSPs were evaluated, with a focus on whether silica with varying dissolution characteristics influences cell viability and drug release (CLZ). All types of soluble silica exhibited low immunological responses, emphasizing the potential and safety of amorphous silica for pulmonary drug delivery. A further innovation in this thesis was the design of bioinspired lung surfactantcoated MSPs, aimed at enhancing CLZ dissolution and improving particle interaction and transport in mucus and bronchial tissue. Finally, the MSPs coating concept was refined using bacterial lipids from mycobacteria to assess whether the antimicrobial activity of CLZ against mycobacteria could be improved, presenting a novel approach for treating lung infections. Overall, this thesis highlights the potential of bioinspired coated MSPs as an advanced drug delivery system to address unmet challenges in treating respiratory infections and in overcoming antimicrobial resistance. 

Place, publisher, year, edition, pages
Malmö: Malmö University Press, 2025. p. 89
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383, E-ISSN 2004-9277 ; 2025:6
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:mau:diva-75084 (URN)10.24834/isbn.9789178776290 (DOI)978-91-7877-628-3 (ISBN)978-91-7877-629-0 (ISBN)
Public defence
2025-04-25, Auditorium E002, Faculty of Health and Society, Jan Waldenströms gata 25, Malmö, 09:15 (English)
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Note

Paper III, IV, V in dissertation as manuscript. Not included in the full text online.

Available from: 2025-04-02 Created: 2025-04-02 Last updated: 2025-04-04Bibliographically approved

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Rocío Hernández, AuraBogdanova, EkaterinaCampos Pacheco, Jesus EnriqueKocherbitov, VitalyValetti, Sabrina

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Rocío Hernández, AuraBogdanova, EkaterinaCampos Pacheco, Jesus EnriqueKocherbitov, VitalyValetti, Sabrina
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