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  • 1. Afonso, Damien
    et al.
    Valetti, Sabrina
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Fraix, Aurore
    Bascetta, Claudia
    Petralia, Salvatore
    Conoci, Sabrina
    Feiler, Adam
    Sortino, Salvatore
    Multivalent mesoporous silica nanoparticles photodelivering nitric oxide with carbon dots as fluorescent reporters2017In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 9Article in journal (Refereed)
    Abstract [en]

    Amino-terminated mesoporous silica nanoparticles embedding carbon dots (MSCD) formed by calcination were functionalized with a nitric oxide (NO) photodonor (1) to give a robust MSCD-1 conjugate. The intense fluorescence of MSCDs was strongly quenched in MSCD-1 by effective energy transfer. Visible light excitation of MSCD-1 liberates NO, suppresses the energy transfer mechanism and leads to concomitant fluorescence restoration of the MSCD scaffold, which acts as an optical reporter for the released NO. The MSCD-1 hybrid is also able to encapsulate the highly hydrophobic photosensitizer temoporfin, preserving the fluorescence reporting function.

  • 2. Angiolini, Lorenzo
    et al.
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Cohen, Boiko
    Feiler, Adam
    Douhal, Abderrazzak
    Fluorescence imaging of antibiotic clofazimine encapsulated within mesoporous silica particle carriers: relevance to drug delivery and the effect on its release kinetics2018In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 20, no 17, p. 11899-11911Article in journal (Refereed)
    Abstract [en]

    We report on the encapsulation of the antibiotic clofazimine (CLZ) within the pores of mesoporous silica particles having hydrophilic (CBET value of 137) and more hydrophobic (CBET value of 94 after calcination at 600 °C) surfaces. We studied the effect of pH on the released amount of CLZ in aqueous solutions and observed a maximum at pH 4.1 in correlation with the solubility of the drug. Less release of the drug was observed from the more hydrophobic particles which was attributed to a difference in the affinity of the drug to the carrier particles. Fluorescence lifetime imaging microscopy, emission spectra, and fluorescence lifetimes of single drug loaded particles provided detailed understanding and new knowledge of the physical form of the encapsulated drug and the distribution within the particles. The distribution of CLZ within the particles was independent of the surface chemistry of the particles. The confirmation of CLZ molecules as monomers or aggregates was revealed by controlled removal of the drug with solvent. Additionally, the observed optical "halo effect" in the fluorescent images was interpreted in terms of specific quenching of high concentration of molecules. The emission lifetime experiments suggest stronger interaction of CLZ with the more hydrophobic particles, which is relevant to its release. The results reported in this work demonstrate that tuning the hydrophilicity/hydrophobicity of mesoporous silica particles can be used as a tool to control the release without impacting their loading ability.

  • 3.
    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..
    Ekstrom, 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)
  • 4.
    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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  • 5.
    Gidvall, Sanna
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Feiler, Adam
    Nanologica AB; KTH, Royal Institute of Technology.
    Dahlström, Bengt
    CTC Clinical Trial Consultants AB.
    Rönn, Robert
    Orexo AB.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    A novel versatile flow-donor chamber as biorelevant ex-vivo test assessing oral mucoadhesive formulations2021In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 166, article id 105983Article in journal (Refereed)
    Abstract [en]

    Oral transmucosal drug delivery is a non-invasive administration route for rapid therapeutic onset and greater bioavailability avoiding the first-pass metabolism. Mucoadhesive formulations are advantageous as they may retain the drug at the administration site. Proper equipment to assess mucoadhesive properties and corresponding drug absorption is fundamental for the development of novel drug delivery systems. Here we developed a new flow-through donor chamber for well-established diffusion cells, and we tested the effects on drug and formulation retention in situ of adding mucoadhesive polymers or mesoporous silica particles to a reference formulation. Mesoporous silica particles are of particular interest as they may be used to encapsulate and retain drug molecules. Compared to other ex-vivo methods described in literature for assessing mucoadhesive performance and transmucosal drug delivery, this new donor chamber provides several advantages: i) it reflects physiological conditions better as a realistic saliva flow can be provided over the administration site, ii) it is versatile since it can be mounted on any kind of vertical diffusion cell allowing simultaneous detection of drug retention at the administration site and drug permeation through the tissue, and iii) it enables optical quantification of formulations residence time aided by image processing. This new flow-through donor diffusion cell set-up proved sensitive to differentiate a reference formulation from one where 20 %(w/w) Carbomer was added (to further improve the mucoadhesive properties), with respect to both drug and formulation residence times. We also found that mesoporous silica particles, investigated as particles only and mixed together with the reference formulation, gave very similar drug and formulation retention to what we observed with the mucoadhesive Carbomer. However, after some time (>30 min) it became obvious that the tablet excipients in the reference formulation promote particle retention on the mucosa. This work provides a new simple and versatile biorelevant test for the evaluation of oral mucoadhesive formulations and paves the way for further studies on mesoporous silica particles as valuable excipients for enhancing oral mucoadhesion.

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  • 6.
    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..
    Ekstrom, 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)
  • 7.
    Riaz, Azra
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Gidvall, Sanna
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Prgomet, Zdenka
    Malmö University, Faculty of Odontology (OD).
    Hernandez, Aura Rocio
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Nilsson, Emelie J.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Davies, Julia R
    Malmö University, Faculty of Odontology (OD). Malmö University, Biofilms Research Center for Biointerfaces.
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Three-Dimensional Oral Mucosal Equivalents as Models for Transmucosal Drug Permeation Studies2023In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 15, no 5, p. 1513-1513Article in journal (Refereed)
    Abstract [en]

    Oral transmucosal administration, where drugs are absorbed directly through the non-keratinized, lining mucosa of the mouth, represents a solution to drug delivery with several advantages. Oral mucosal equivalents (OME) developed as 3D in vitro models are of great interest since they express the correct cell differentiation and tissue architecture, simulating the in vivo conditions better than monolayer cultures or animal tissues. The aim of this work was to develop OME to be used as a membrane for drug permeation studies. We developed both full-thickness (i.e., connective plus epithelial tissue) and split-thickness (i.e., only epithelial tissue) OME using non-tumor-derived human keratinocytes OKF6 TERT-2 obtained from the floor of the mouth. All the OME developed here presented similar transepithelial electrical resistance (TEER) values, comparable to the commercial EpiOral™. Using eletriptan hydrobromide as a model drug, we found that the full-thickness OME had similar drug flux to EpiOral™ (28.8 vs. 29.6 µg/cm2/h), suggesting that the model had the same permeation barrier properties. Furthermore, full-thickness OME showed an increase in ceramide content together with a decrease in phospholipids in comparison to the monolayer culture, indicating that lipid differentiation occurred due to the tissue-engineering protocols. The split-thickness mucosal model resulted in 4–5 cell layers with basal cells still undergoing mitosis. The optimum period at the air–liquid interface for this model was twenty-one days; after longer times, signs of apoptosis appeared. Following the 3R principles, we found that the addition of Ca2+, retinoic acid, linoleic acid, epidermal growth factor and bovine pituitary extract was important but not sufficient to fully replace the fetal bovine serum. Finally, the OME models presented here offer a longer shelf-life than the pre-existing models, which paves the way for the further investigation of broader pharmaceutical applications (i.e., long-term drug exposure, effect on the keratinocytes’ differentiation and inflammatory conditions, etc.).

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  • 8. Stjern, Louise
    et al.
    Voittonen, Sandra
    Weldemichel, Rahel
    Thuresson, Sofia
    Agnes, Marco
    Benkovics, Gabor
    Fenyvesi, Eva
    Malanga, Milo
    Yannakopoulou, Konstantina
    Feiler, Adam
    Valetti, Sabrina
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Cyclodextrin-mesoporous silica particle composites for controlled antibiotic release. A proof of concept toward colon targeting2017In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 531, no 2, p. 595-605Article in journal (Refereed)
    Abstract [en]

    Cyclodextrins (CDs) and mesoporous silica particles (MSPs) have been combined as composite carriers for controlled antibiotic release. CDs were employed as "gatekeeper" agents and grafted onto MSPs to retain drug molecules inside the MSP carrier. A variety of CDs (unfunctionalized, positively charged and carboxymethylated) and three different coupling strategies (covalent binding, electrostatic adsorption and inclusion complexation) were systematically investigated for their ability to control the release of two antibiotic drugs, metronidazole and clofazimine. The drugs had significantly different physicochemical properties (metronidazole - small hydrophilic, clofazimine- large hydrophobic). We report for the first time on the encapsulation and characterization of metronidazole-loaded-MSP. Each CD coating strategy reduced the drug release rate in phosphate buffer compared to unmodified MSP (from 20% to 100% retained drug). Covalent binding and inclusion complex approaches were significantly more effective than electrostatically adsorbed CD. In particular, the novel inclusion complex based on host/guest interaction between benzyl-modified silica surface and alpha-CD proved to be very effective (60-100% retained drug amount). Using pharmaceutical manufacturing processes, our study shows that CD-MSP composites can retain both hydrophobic and hydrophilic antibiotic compounds with potential translation to triggered release formulation targeting bacterial infections in the colon and lower intestine.

  • 9.
    Valetti, Sabrina
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Feiler, Adam
    Martin, Trulsson
    Bare and Effective Charge of Mesoporous Silica Particles2017In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 33, p. 7343-7351Article in journal (Refereed)
    Abstract [en]

    We develop and combine a novel numerical model, within the Poisson−Boltzmann framework, with classical experimental titration techniques for mesoporous silica particles to study the charging behavior as both pH and the amount of monovalent salt are varied. One key finding is that these particles can be considered to have an effectively or apparent electroneutral inner core with an effectively charged rim. As a consequence, the total apparent charge of the particle is several orders of magnitude smaller than that of the bare silica charge, which accounts only for the charged silanol groups of the mesoporous silica particles and which has its major contribution from the interior. Hence, the interior dictates the mesoporous silicas’ bare charge while the rim its effective charge. We furthermore report density, charge, and accumulated charge profiles across the particle’s interface.

  • 10.
    Valetti, Sabrina
    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.
    Doko, Anemona
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Sultana, Kaiser
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Eskandari, Mahboubeh
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Prgomet, Zdenka
    Malmö University, Faculty of Odontology (OD).
    Feiler, Adam
    Nanologica AB, 151 36 Södertälje, Sweden; Chemistry Department, KTH, Royal Institute of Technology, 100 44 Stockholm, Sweden.
    Rönn, Robert
    Orexo AB, 754 50 Uppsala, Sweden.
    Dahlström, Bengt
    CTC Clinical Trial Consultants AB, 75237 Uppsala, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Oral transmucosal delivery of eletriptan for neurological diseases.2022In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 627, article id 122222Article in journal (Refereed)
    Abstract [en]

    Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pKa of EB falls within the physiologically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.

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  • 11.
    Valetti, Sabrina
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Nanologica AB.
    Thomsen, Hanna
    University of Gothenburg.
    Wankar, Jitendra
    Istituto per la Sintesi Organica e la Fotoreattività, Italy.
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Manet, Ilse
    Istituto per la Sintesi Organica e la Fotoreattività, Italy.
    Feiler, Adam
    Nanologica AB; KTH.
    Ericson, Marica B
    University of Gothenburg.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Can mesoporous nanoparticles promote bioavailability of topical pharmaceutics?2021In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 602, article id 120609Article in journal (Refereed)
    Abstract [en]

    When applied to skin, particulate matter has been shown to accumulate in hair follicles. In addition to follicles, the skin topography also incorporates trench-like furrows where particles potentially can accumulate; however, the furrows have not been as thoroughly investigated in a drug delivery perspective. Depending on body site, the combined follicle orifices cover up to 10% of the skin surface, while furrows can easily cover 20%, reaching depths exceeding 25 µm. Hence, porous particles of appropriate size and porosity could serve as carriers for drugs to be released in the follicles prior to local or systemic absorption. In this paper, we combine multiphoton microscopy, scanning electron microscopy, and Franz cell diffusion technology to investigate ex-vivo skin accumulation of mesoporous silica particles (average size of 400-600 nm, 2, and 7 µm, respectively), and the potential of which as vehicles for topical drug delivery of the broad-spectrum antibiotic metronidazole. We detected smaller particles (400-600 nm) in furrows at depths of about 25 µm, also after rinsing, while larger particles (7 µm) where located more superficially on the skin. This implies that appropriately sized porous particles may serve as valuable excipients in optimizing bioavailability of topical formulations. This work highlights the potential of skin furrows for topical drug delivery.

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  • 12.
    Valetti, Sabrina
    et al.
    Nanologica AB, Södertälje, Sweden.
    Wankar, Jitendra
    Ericson, Marica B.
    Feiler, Adam
    Manet, Ilse
    Mesoporous silica particles as lipophilic drug vehicle investigated by fluorescence lifetime imaging2017In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, no 17Article in journal (Refereed)
    Abstract [en]

    Three types of new label-free fluorescent mesoporous silica micro- and nanoparticles were prepared by controlled thermal decomposition of carboamino groups linked on the surface without compromising the drug loading capacity of the silica particles. Clofazimine, a lipophilic antibiotic drug with excellent in vitro activity against mycobacterium tuberculosis, was encapsulated inside these fluorescent particles to obtain multifunctional drug carriers of interest in the field of theranostics. The morphological features together with the photophysical properties of both powders and aqueous suspensions are described. The photophysical properties seem to be independent of the mesoporosity features but correlate with the residual carboamino functionalization. The particles are endowed with emission in the visible region and have fluorescence lifetimes of up to 9.0 ns that can be easily discriminated from intrinsic biological fluorescence. Furthermore, their fluorescence lifetime offers a promising tool to follow the release of the encapsulated drug which is not possible by means of simple fluorescence intensity. We report here a novel attractive theranostic platform enabling monitoring of drug release in biological environments by means of fluorescence lifetime.

  • 13.
    Valetti, Sabrina
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Xia, Xin
    Costa-Gouveia, Joana
    Brodin, Priscille
    Bernet-Camard, Marie-Françoise
    Andersson, Margareta
    Feiler, Adam
    Clofazimine encapsulation in nanoporous silica particles for the oral treatment of antibiotic resistant M. tuberculosis infections2017In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 12, no 8Article in journal (Refereed)
    Abstract [en]

    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.

  • 14.
    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)
  • 15. Zhou, Chunfang
    et al.
    Afonso, Damien
    Valetti, Sabrina
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Feiler, Adam
    Cardile, Venera
    Graziano, Adriana C.E.
    Conoci, Sabrina
    STMicroelectronics, Stradale Primosole 50, 95121, Catania, Italy.
    Sortino, Salvatore
    Targeted Photodynamic Therapy with a Folate/Sensitizer Assembly Produced from Mesoporous Silica2017In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 23, no 32, p. 7672-7676Article in journal (Refereed)
    Abstract [en]

    A mesoporous silica material prepared by using folic acid (FA) as a template enables the effective encapsulation of meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP) in its interior. Combination of steady-state and time-resolved absorption and emission spectroscopy demonstrate that FA and TCPP are released from the silica material to the aqueous phase in the form of a non-covalent assembly. This assembly does not form by simple mixing of the two components in the absence of silica, suggesting the key role of the material in the assembling process. The FA/TCPP assembly exhibits dual color fluorescence in the visible region, good photosensitization capability of singlet oxygen, and enhanced photo-induced mortality in KB cancer cells overexpressing folate receptor, if compared with the free components.

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