| 1. |
- Björk, Emma, et al.
(författare)
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Cell adherence and drug delivery from particle based mesoporous silica films
- 2019
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Ingår i: RSC Advances. - : ROYAL SOC CHEMISTRY. - 2046-2069. ; 9:31, s. 17745-17753
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Tidskriftsartikel (refereegranskat)abstract
- Spatially and temporally controlled drug delivery is important for implant and tissue engineering applications, as the efficacy and bioavailability of the drug can be enhanced, and can also allow for drugging stem cells at different stages of development. Long-term drug delivery over weeks to months is however difficult to achieve, and coating of 3D surfaces or creating patterned surfaces is a challenge using coating techniques like spin- and dip-coating. In this study, mesoporous films consisting of SBA-15 particles grown onto silicon wafers using wet processing were evaluated as a scaffold for drug delivery. Films with various particle sizes (100-900 nm) and hence thicknesses were grown onto trichloro(octadecyl)silane-functionalized silicon wafers using a direct growth method. Precise patterning of the areas for film growth could be obtained by local removal of the OTS functionalization through laser ablation. The films were incubated with the drug model 3,3 -dioctadecyloxacarbocyanine perchlorate (DiO), and murine myoblast cells (C2C12 cells) were seeded onto films with different particle sizes. Confocal laser scanning microscopy (CLSM) was used to study the cell growth, and a vinculin-mediated adherence of C2C12 cells on all films was verified. The successful loading of DiO into the films was confirmed by UV-vis and CLSM. It was observed that the drugs did not desorb from the particles during 24 hours in cell culture. During adherent growth on the films for 4 h, small amounts of DiO and separate particles were observed inside single cells. After 24 h, a larger number of particles and a strong DiO signal were recorded in the cells, indicating a particle mediated drug uptake. The vast majority of the DiO-loaded particles remained attached to the substrate also after 24 h of incubation, making the films attractive as longer-term reservoirs for drugs on e.g. medical implants.
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| 2. |
- Braun, Katharina, et al.
(författare)
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Membrane interactions of mesoporous silica nanoparticles as carriers of antimicrobial peptides
- 2016
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 475, s. 161-170
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Tidskriftsartikel (refereegranskat)abstract
- Membrane interactions are critical for the successful use of mesoporous silica nanoparticles as delivery systems for antimicrobial peptides (AMPs). In order to elucidate these, we here investigate effects of nanoparticle charge and porosity on AMP loading and release, as well as consequences of this for membrane interactions and antimicrobial effects. Anionic mesoporous silica particles were found to incorporate considerable amounts of the cationic AMP LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (LL-37), whereas loading is much lower for non-porous or positively charged silica nanoparticles. Due to preferential pore localization, anionic mesoporous particles, but not the other particles, protect LL-37 from degradation by infection-related proteases. For anionic mesoporous nanoparticles, membrane disruption is mediated almost exclusively by peptide release. In contrast, non-porous silica particles build up a resilient LL-37 surface coating due to their higher negative surface charge, and display largely particle-mediated membrane interactions and antimicrobial effects. For positively charged mesoporous silica nanoparticles, LL-37 incorporation promotes the membrane binding and disruption displayed by the particles in the absence of peptide, but also causes toxicity against human erythrocytes. Thus, the use of mesoporous silica nanoparticles as AMP delivery systems requires consideration of membrane interactions and selectivity of both free peptide and the peptide-loaded nanoparticles, the latter critically dependent on nanoparticle properties.
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| 3. |
- Frykstrand Ångström, Sara, 1987-
(författare)
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Mesoporous magnesium carbonate : Synthesis, characterization and biocompatibility
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mesoporous materials constitute a promising class of nanomaterials for a number of applications due to their tunable pore structure. The synthesis of most mesoporous materials involves a surfactant liquid crystal structure to form the pores. As well as the many advantages associated with this method of synthesis, there are disadvantages such as high production costs and a substantial environmental impact which limit the possibilities for large scale production. Therefore there is a need for other synthesis routes.The aim of the work described herein was to contribute to this field by developing a synthesis route that does not rely on surfactants for pore formation. A mesoporous magnesium carbonate material was therefore formed by self-assemblage of the particles around carbon dioxide gas bubbles, which functioned as pore templates. It was also possible to vary the pore diameter between 3 and 20 nm.The biocompatibility of the formed magnesium carbonate material was evaluated in terms of in vitro cytotoxicity and hemocompatibility, in vivo skin irritation and acute systemic toxicity. The results from the in vitro cytotoxicity, in vivo skin irritation and acute systemic toxicity test using a polar extraction vehicle showed that the material was non-toxic. While signs of toxicity were observed in the acute systemic toxicity test using a non-polar solvent, this was attributed to injection of particles rather than toxic leachables. In the in vitro hemocompatibility test, no hemolytic activity was found with material concentrations of up to 1 mg/ml. It was further shown that the material had anticoagulant properties and induced moderate activation of the complement system. The anticoagulant properties were ascribed to uptake of Ca2+.Finally, the ability of the material to increase the dissolution rate of the poorly soluble drug itraconazole was analyzed. Itraconazole was dissolved up to 23 times faster from the magnesium carbonate pores than when the free drug was used. The release rate from the delivery vehicle was dependent on the pore diameter.The work presented herein is expected to be useful for the development of alternative synthesis routes for mesoporous materials and also for encouraging the development of biomedical applications for these materials.
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| 4. |
- Mutschler, Anna, et al.
(författare)
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Mesoporous Silica-gold Films for Straightforward, Highly Reproducible Monitoring of Mercury Traces in Water
- 2019
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Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Trace-level detection of mercury in waters is connected with several complications including complex multistep analysis routines, applying additional, harmful reagents increasing the risk of contamination, and the need for expensive analysis equipment. Here, we present a straightforward reagent-free approach for mercury trace determination using a novel thin film sampling stick for passive sampling based on gold nanoparticles. The nanoparticles supported on a silicon wafer and further covered with a thin layer of mesoporous silica. The mesoporous silica layer is acting as a protection layer preventing gold desorption upon exposure to water. The gold nanoparticles are created by thermal treatment of a homogenous gold layer on silicon wafer prepared by vacuum evaporation. This gold-covered substrate is subsequently covered by a layer of mesoporous silica through dip-coating. Dissolved mercury ions are extracted from a water sample, e.g., river water, by incorporation into the gold matrix in a diffusion-controlled manner. Thus, the amount of mercury accumulated during sampling depends on the mercury concentration of the water sample, the accumulation time, as well as the size of the substrate. Therefore, the experimental conditions can be chosen to fit any given mercury concentration level without loss of sensitivity. Determination of the mercury amount collected on the stick is performed after thermal desorption of mercury in the gas phase using atomic fluorescence spectrometry. Furthermore, the substrates can be re-used several tens of times without any loss of performance, and the batch-to-batch variations are minimal. Therefore, the nanogold-mesoporous silica sampling substrates allow for highly sensitive, simple, and reagent-free determination of mercury trace concentrations in waters, which should also be applicable for on-site analysis. Successful validation of the method was shown by measurement of mercury concentration in the certified reference material ORMS-5, a river water.
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| 5. |
- Tenland, Erik, et al.
(författare)
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Effective delivery of the anti-mycobacterial peptide NZX in mesoporous silica nanoparticles
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy. Methods and findings We have previously identified a peptide, called NZX, capable of inhibiting both clinical and multi-drug resistant strains of M. tuberculosis at therapeutic concentrations. In this study we analysed the potential of MSPs containing NZX for the treatment of tuberculosis. The MSPs released functional NZX gradually into simulated lung fluid and the peptide filled MSPs were easily taken up by primary macrophages. In an intracellular infection model, the peptide containing particles showed increased mycobacterial killing compared to free peptide. The therapeutic potential of peptide containing MSPs was investigated in a murine infection model, showing that MSPs preserved the effect to eliminate M. tuberculosis in vivo. Conclusions In this study we found that loading the antimicrobial peptide NZX into MSPs increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M. tuberculosis in vivo in a murine model. Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis.
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| 6. |
- Yang, Jiaojiao
(författare)
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Amorphous magnesium carbonate nanomaterials : Synthesis, characterization and applications
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- High surface-to-volume ratio materials, including nanoparticles and mesoporous materials, have a number of applications due to their large surface area and special structures. Traditional approaches for synthesizing high surface-to-volume ratio nanomaterials are often complicated, expensive or environmentally unfriendly. Considering aspects such as availability and safety in terms of environmental or biological contact, magnesium carbonate-based nanomaterials are an interesting and potentially valuable candidate for novel applications. The overall aim of this thesis was to develop novel high surface-to-volume ratio amorphous magnesium carbonate nanomaterials and investigating their possible applications.Amorphous magnesium carbonate nanoparticles (AMN) were successfully synthesized via a simple and low-temperature pathway. The structure and resulting properties of the material can be tailored by changing the final steps in the synthesis process.The ability of AMN to stabilize ibuprofen (IBU) in the amorphous state was investigated. Nanocomposites with IBU:AMN mass ratios as high as to 5:1 were shown to enhance the release rate of IBU in vitro by as much as 83 times compared to IBU in crystalline form. A related nanostructured material, mesoporous magnesium carbonate (MMC), was evaluated as a drug carrier for stabilizing amorphous drugs through the incorporation of the drug within its pores. In this study, MMC was used to release and sustain two poorly soluble drugs (tolfenamic acid and rimonabant) in the supersaturated state with the assistance of hydroxypropyl methylcellulose.AMN was also used to synthesize a novel adhesive together with IBU without the addition of a polymer. This adhesive was transparent, self-healing, shapeable, stretchable and reusable. In addition, the adhesive was able to glue a variety of materials, including metals, glass, paper and plastics (even Teflon).Finally, AMN was used to prepare flexible, transparent and UV-shielding films when incorporated into a PMMA matrix. These films exhibited both UV-shielding properties and moisture absorbance and retention abilities. In addition, the UV- and thermo-stability of these films were enhanced by the addition of AMN.The work presented in this thesis show that the nanomaterials AMN and MMC possess great potential for an extremely broad range of applications, from pharmaceutical applications dealing with poorly soluble drugs to structural applications such as adhesives to applications in optics or electronics such as UV-shielding or moisture barrier films.
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