| 1. |
- Afonso, Damien, et al.
(författare)
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Multivalent mesoporous silica nanoparticles photo-delivering nitric oxide with carbon dots as fluorescence reporters
- 2017
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Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 9:36, s. 13404-13408
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Afonso, Damien, et al.
(författare)
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Multivalent mesoporous silica nanoparticles photodelivering nitric oxide with carbon dots as fluorescent reporters
- 2017
-
Ingår i: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Angiolini, Lorenzo, et al.
(författare)
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Fluorescence imaging of antibiotic clofazimine encapsulated within mesoporous silica particle carriers : relevance to drug delivery and the effect on its release kinetics
- 2018
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 20:17, s. 11899-11911
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
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| 5. |
- Campos Pacheco, Jesús Enrique, et al.
(författare)
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Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis
- 2024
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Ingår i: Journal of Controlled Release. - : Elsevier B.V.. - 0168-3659 .- 1873-4995. ; 369, s. 231-250
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 6. |
- Corkery, Robert W., 1967-, et al.
(författare)
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Anti-caking agent for flavored products
- 2010
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Patent (populärvet., debatt m.m.)abstract
- The present invention generally relates to the use of porous particles to control the release of a liquid, such as the release of a flavor in a food product. Liquid components, such as flavorants, are loaded into porous particles to form a composition. The pore diameter, pore tortuosity and loading parameters determine the characteristics of the composition and the release profile of the liquid.
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| 7. |
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| 8. |
- Feiler, Adam A., et al.
(författare)
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Adsorption and viscoelastic properties of fractionated mucin (BSM) and bovine serum albumin (BSA) studied with quartz crystal microbalance (QCM-D)
- 2007
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 315:2, s. 475-481
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption profile and viscoelastic properties of bovine submaxillary gland mucin (BSM) and bovine serum albumin (BSA), extracted from a commercial mucin preparation, adsorbing to polystyrene surfaces has been studied using quartz crystal microbalance with dissipation monitoring (QCM-D). A significant difference in the adsorption properties of the different proteins was detected; with the BSA adsorbing in a flat rigid layer whilst the mucin adsorbed in a diffuse, highly viscoelastic layer. Subsequent addition of BSA to the preadsorbed mucin layer resulted in stiffening of the protein layer which was attributed to complexation of the mucin by BSA. In contrast, a preadsorbed layer of BSA prevented mucin adsorption altogether. Combined mixtures of mucin and BSA in well defined ratios revealed intermediate properties between the two separate protein species which varied systematically with the protein ratios. The results shed light on the synergistic effects of complexation of lower molecular weight biomolecular species with mucin. The possibility to selectively control protein uptake and tailor the physical properties of the adsorbed layer makes mucin an attractive option for application in biomaterial coatings.
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| 9. |
- Feiler, Adam A., et al.
(författare)
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Adsorption of anionic gold nanoparticles by a layer of cationic microgel particles deposited on a gold-coated, quartz surface : studied by quartz crystal microbalance and atomic force microscopy
- 2011
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 7:14, s. 6660-6670
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Tidskriftsartikel (refereegranskat)abstract
- The uptake of gold [Au-MES] nanoparticles by pH-responsive poly(2-vinylpyridine) [P2VP] microgel particles, deposited on a surface, has been studied using a quartz crystal microbalance with dissipation monitoring [QCM-D]. QCM-D, which has not previously been applied to such systems, has been shown to be a promising technique for their analysis, especially when combined with a complementary technique such as atomic force microscopy [AFM]. The QCM-D technique, which provides information on mass and viscosity changes of material adsorbed to a surface, has been used to follow the adsorption of microgel particles to a surface, their subsequent swelling and collapse due to changing the system pH, and the uptake of Au-MES nanoparticles by the P2VP particles. Microgel particles with differing cross-linker content have been compared, following uptake by microgel particles in both their collapsed and swollen states. Qualitative differences in the QCM-D response were observed between microgels with differing cross-linker content (and hence different swelling properties). It was shown that uptake of Au-MES nanoparticles acted to fully and irreversibly collapse the swollen P2VP microgels, inhibiting their pH response. The Sauerbrey relationship was used to equate frequency changes measured by QCM-D to mass allowing sorption amounts for the uptake of Au-MES nanoparticles by P2VP particles to be obtained for these surface-constrained systems.
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| 10. |
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| 11. |
- Feiler, Adam, et al.
(författare)
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Effect of capillary condensation on friction force and adhesion
- 2007
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 23:2, s. 517-522
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Tidskriftsartikel (refereegranskat)abstract
- Friction force measurements have been conducted with a colloid probe on mica and silica (both hydrophilic and hydrophobised) after long (24 hour) exposure to high humidity air. Adhesion and friction measurements have also been performed on cellulose substrates. The long exposure to high humidity led to a large hysteresis between loading and unloading in the friction measurements with separation occurring at large negative applied loads. The large hysteresis in the friction-load relationship is attributed to a contact area hysteresis of the capillary condensate which built up during loading and did not evaporate during the unloading regime. The magnitude of the friction force varied dramatically between substrates and was lowest on the mica substrate and highest on the hydrophilic silica substrate with the hydrophobised silica and cellulose being intermediate. The adhesion due to capillary forces on cellulose was small compared to that on the other substrates, due to the greater roughness of these surfaces.
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| 12. |
- Feiler, Adam, et al.
(författare)
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Effect of relative humidity on adhesion and frictional properties of micro- and nano-scopic contacts
- 2005
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Ingår i: Journal of Adhesion Science and Technology. - : Informa UK Limited. - 0169-4243 .- 1568-5616. ; 19:05-mar, s. 165-179
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Tidskriftsartikel (refereegranskat)abstract
- The effect of relative humidity (RH) oil the interactions of AFM tips and colloidal probes with hydrophilic silica substrates is investigated. Both friction and adhesion are studied. For the case of a colloidal probe the interaction is characteristic of a multiasperity contact, the adhesion increased with increasing RH and above a certain threshold relative humidity a large increase in adhesion was measured. This behaviour is explained in terms of a recent model where the Kelvin radius of the condensate becomes larger than some characteristic roughness on the surface. The interaction between the tip and the substrate also exhibited an increase in adhesion above a threshold RH although the increase was much less marked than with the colloid probe. The friction decreased with increasing humidity for both tip and colloid probe although the friction force was much less sensitive than adhesion to changes in RH. Stick-slip behaviour was observed between tip and substrate for all humidities at high loads, but only at the lowest RH (about 5%) it was observed at all loads. At higher humidity the behaviour became increasingly continuum on the experimental timescale, presumably due to viscous contributions from the water. Stick-slip was not observed for the colloidal probe friction measurements.
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| 13. |
- Garcia-Bennett, Alfonso, et al.
(författare)
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Mesoporous ASD : Fundamentals
- 2014
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Ingår i: Amorphous Solid Dispersions. - New York : Springer. - 9781493915989 - 9781493915972 ; , s. 637-663
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Bokkapitel (refereegranskat)abstract
- Mesoporous silica materials are having an impact in traditional pharmaceutical applications and nanomedicine. As excipients, they are allowing the enhancement of poorly soluble drugs with significant improvements in solubility for a large variety of type II drug compounds. Synthetic and structural versatility allows to truly design both mesopore structure and mesopore size with great precision promising to allow for a library of standard materials that can deliver tailored pharmacokinetic release profiles. In this chapter, we highlight some of the important developments in the field of mesoporous materials focusing on early synthetic aspects as well as later functionalisation strategies. The characterisation methods that are employed commonly and may be used to facilitate production and quality assessment are also discussed. Finally, we update the reader with some brief examples of how these non-toxic and biocompatible vehicles are entering pharmaceutical applications.
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| 14. |
- Gidvall, Sanna, et al.
(författare)
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A novel versatile flow-donor chamber as biorelevant ex-vivo test assessing oral mucoadhesive formulations
- 2021
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 166
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 15. |
- Gross, Sean M., et al.
(författare)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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| 16. |
- Halthur, Tobias J, et al.
(författare)
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Sequential adsorption of bovine mucin and lactoperoxidase to various substrates studied with quartz crystal microbalance with dissipation
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:7, s. 4901-4908
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Tidskriftsartikel (refereegranskat)abstract
- Mucin and lactoperoxidase are both natively present in the human saliva. Mucin provides lubricating and antiadhesive function, while lactoperoxidase has antimicrobial activity. We propose that combined Films of the two proteins can be used as a strategy for surface modification in biomedical applications such as implants or biosensors. In order to design and ultilize mixed protein films, it is necessary to understand the variation in adsorption behavior of the proteins onto different surfaces and how it affects their interaction. The quartz crystal microbalance with dissipation (QCM-D) technique hats been used to extract information of the adsorption properties of bovine mucin (BSM) and lactoperoxidase (LPO) to gold, silica. and hydrophobized silica surfaces. The information has further been used to retrieve information of the viscoelastic properties of the adsorbed film. The adsorption and compaction of BSM were found to vary depending on the nature of the underlying bare surface, adsorbing as at thick highly hydrated film with loops and tails extending out in the bulk on gold and as a thinner film with much lower adsorbed amount on silica; and on hydrophobic surfaces, BSM adsorbs as a flat and much more compact layer. On gold and silica, the highly hydrated BSM film is cross-linked and compacted by the addition of LPO, whereas the compaction is not as pronounced on the already more compact film formed on hydrophobic surfaces. The adsorption of LPO to bare surfaces also varied depending on the type of surface. The adsorption profile of BSM onto LPO-coated surfaces mimicked the adsorption to the underlying surface, implying little interaction between the LPO and BSM. The interaction between the protein layers was interpreted as a combination of electrostatic and hydrophobic interactions, which was in turn influenced by the interaction of the proteins with the different substrates.
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| 17. |
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| 18. |
- Leyton-Jaimes, M. F., et al.
(författare)
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Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS
- 2020
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a devastating incurable neurological disorder characterized by motor neuron (MN) death and muscle dysfunction leading to mean survival time after diagnosis of only 2–5 years. A potential ALS treatment is to delay the loss of MNs and disease progression by the delivery of trophic factors. Previously, we demonstrated that implanted mesoporous silica nanoparticles (MSPs) loaded with trophic factor peptide mimetics support survival and induce differentiation of co-implanted embryonic stem cell (ESC)-derived MNs. Here, we investigate whether MSP loaded with peptide mimetics of ciliary neurotrophic factor (Cintrofin), glial-derived neurotrophic factor (Gliafin), and vascular endothelial growth factor (Vefin1) injected into the cervical spinal cord of mutant SOD1 mice affect disease progression and extend survival. We also transplanted boundary cap neural crest stem cells (bNCSCs) which have been shown previously to have a positive effect on MN survival in vitro and in vivo. We show that mimetic-loaded MSPs and bNCSCs significantly delay disease progression and increase survival of mutant SOD1 mice, and also that empty particles significantly improve the condition of ALS mice. Our results suggest that intraspinal delivery of MSPs is a potential therapeutic approach for the treatment of ALS.
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| 19. |
- Pettersson, Torbjörn, et al.
(författare)
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Comparison of different methods to calibrate torsional spring constant and photodetector for atomic force microscopy friction measurements in air and liquid
- 2007
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 78:9, s. 093702-
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Tidskriftsartikel (refereegranskat)abstract
- A number of atomic force microscopy cantilevers have been exhaustively calibrated by a number of techniques to obtain both normal and frictional force constants to evaluate the relative accuracy of the different methods. These were of either direct or indirect character-the latter relies on cantilever resonant frequencies. The so-called Sader [Rev. Sci. Instrum. 70, 3967 (1999)] and Cleveland [Rev. Sci. Instrum. 64, 403 (1993)] techniques are compared for the normal force constant calibration and while agreement was good, a systematic difference was observed. For the torsional force constants, all the techniques displayed a certain scatter but the agreement was highly encouraging. By far the simplest technique is that of Sader, and it is suggested in view of this validation that this method should be generally adopted. The issue of the photodetector calibration is also addressed since this is necessary to obtain the cantilever twist from which the torsional force is calculated. Here a technique of obtaining the torsional photodetector sensitivity by combining the direct and indirect methods is proposed. Direct calibration measurements were conducted in liquid as well as air, and a conversion factor was obtained showing that quantitative friction measurements in liquid are equally feasible provided the correct calibration is performed.
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| 20. |
- Sala-Jarque, Júlia, et al.
(författare)
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Mesoporous silica particles are phagocytosed by microglia and induce a mild inflammatory response in vitro
- 2022
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Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 17:15, s. 1077-1094
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Tidskriftsartikel (refereegranskat)abstract
- Aim:Mesoporous silica particles (MSPs) are broadly used drug delivery carriers. In this study, the authors analyzed the responses to MSPs of astrocytes and microglia, the two main cellular players in neuroinflammation.Materials & methods:Primary murine cortical mixed glial cultures were treated with rhodamine B-labeled MSPs.Results:MSPs are avidly internalized by microglial cells and remain inside the cells for at least 14 days. Despite this, MSPs do not affect glial cell viability or morphology, basal metabolic activity or oxidative stress. MSPs also do not affect mRNA levels of key proinflammatory genes; however, in combination with lipopolysaccharide, they significantly increase extracellular IL-1β levels.Conclusion:These results suggest that MSPs could be novel tools for specific drug delivery to microglial cells. Plain language summary Mesoporous silica particles (MSPs) are broadly used drug delivery carriers. In this study, the authors analyzed the responses of two types of brain cells, astrocytes and microglia, to MSPs. Mouse astrocytes and microglia were kept alive in cultures and were treated with MSPs that were labeled with a red fluorescent agent to facilitate visualization under the microscope. MSPs are avidly internalized by microglial cells and remain inside the cells for at least 14 days. Despite this, MSPs do not affect glial cell viability or morphology, basal metabolic activity or oxidative stress. When given alone, MSPs do not affect mRNA levels of key proinflammatory genes. However, MSPs given in combination with lipopolysaccharide, a strong proinflammatory agent, significantly increase extracellular levels of IL-1β, one of the proinflammatory mediators studied. These results suggest that MSPs could be novel tools for specific drug delivery to microglial cells.
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| 21. |
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| 22. |
- Sandberg, Tomas, et al.
(författare)
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Potential use of mucins as biomaterial coatings. II. Mucin coatings affect the conformation and neutrophil-activating properties of adsorbed host proteins – Towards a mucosal mimic
- 2009
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Ingår i: Journal of Biomedical Materials Research: Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 91A:3, s. 773-785
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Tidskriftsartikel (refereegranskat)abstract
- In continuation of our recent fractionation and characterization study on mucins of bovine salivary (BSM), porcine gastric (PGM), and human salivary (MG1) origin, this study evaluates the effect of mucin precoating on the conformation and neutrophil-activating properties of host proteins adsorbed to a polyethylene terephthalate-based model biomaterial. Microscopy combined with assays for the neutrophil releases of reactive oxygen species and human neutrophil lipocalin showed that mucin precoating greatly reduced the strong immune-response normally induced by adsorbed immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), respectively. A similar finding was made for the proinflammatory fibrinogen. Although the total uptakes of these proteins depended on the mucin surface concentration, a detailed composite analysis suggested the fraction Of surface-exposed protein to be a stronger determinant of coating performance. The unexpectedly low neutrophil activation showed by composites containing near-monolayer concentrations of exposed IgG and sIgA, respectively, suggested that these act synergistically with mucin on the surface. In support of this hypothesis, quartz crystal microbalance with dissipation monitoring measurements revealed that a preadsorbed BSM layer stabilizes IgG through complexation on a polymeric model surface. Our findings link well to the complex in vivo situation and suggest that functional mucosal mimics can be created in situ for improved biomaterials performance.
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| 23. |
- Stjern, Louise, et al.
(författare)
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Cyclodextrin-mesoporous silica particle composites for controlled antibiotic release. A proof of concept toward colon targeting
- 2017
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 531:2, s. 595-605
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 24. |
- Valetti, Sabrina, et al.
(författare)
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Bare and Effective Charge of Mesoporous Silica Particles
- 2017
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Ingår i: Langmuir. - : AMER CHEMICAL SOC. - 0743-7463 .- 1520-5827. ; 33:29, s. 7343-7351
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 25. |
- Valetti, Sabrina, et al.
(författare)
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Can mesoporous nanoparticles promote bioavailability of topical pharmaceutics?
- 2021
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 602
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Tidskriftsartikel (refereegranskat)abstract
- 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 mu m. 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 mu m, respectively), and the potential of which as vehicles for topical delivery of the broad-spectrum antibiotic metronidazole. We detected smaller particles (400-600 nm) in furrows at depths of about 25 mu m, also after rinsing, while larger particles (7 mu m) 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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| 26. |
- Valetti, Sabrina, et al.
(författare)
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Clofazimine encapsulation in nanoporous silica particles for the oral treatment of antibiotic resistant M. tuberculosis infections
- 2017
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Ingår i: Nanomedicine. - : Future Medicine. - 1743-5889 .- 1748-6963. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 27. |
- Valetti, S., et al.
(författare)
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Mesoporous silica particles as a lipophilic drug vehicle investigated by fluorescence lifetime imaging
- 2017
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Ingår i: Journal of Materials Chemistry B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 5:17, s. 3201-3211
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 28. |
- Valetti, Sabrina, et al.
(författare)
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Mesoporous silica particles as lipophilic drug vehicle investigated by fluorescence lifetime imaging
- 2017
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; :17
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 29. |
- Valetti, Sabrina, et al.
(författare)
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Oral transmucosal delivery of eletriptan for neurological diseases
- 2022
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 627, s. 122222-
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Tidskriftsartikel (refereegranskat)abstract
- 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 physio-logically 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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| 30. |
- Valle-Delgado, J. J., et al.
(författare)
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Hydration forces between silica surfaces : Experimental data and predictions from different theories
- 2005
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 123, s. 034708-
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Tidskriftsartikel (refereegranskat)abstract
- Silica is a very interesting system that has been thoroughly studied in the last decades. One of the most outstanding characteristics of silica suspensions is their stability in solutions at high salt concentrations. In addition to that, measurements of direct-interaction forces between silica surfaces, obtained by different authors by means of surface force apparatus or atomic force microscope (AFM), reveal the existence of a strong repulsive interaction at short distances (below 2 nm) that decays exponentially. These results cannot be explained in terms of the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory, which only considers two types of forces: the electrical double-layer repulsion and the London-van der Waals attraction. Although there is a controversy about the origin of the short-range repulsive force, the existence of a structured layer of water molecules at the silica surface is the most accepted explanation for it. The overlap of structured water layers of different surfaces leads to repulsive forces, which are known as hydration forces. This assumption is based on the very hydrophilic nature of silica. Different theories have been developed in order to reproduce the exponentially decaying behavior (as a function of the separation distance) of the hydration forces. Different mechanisms for the formation of the structured water layer around the silica surfaces are considered by each theory. By the aid of an AFM and the colloid probe technique, the interaction forces between silica surfaces have been measured directly at different pH values and salt concentrations. The results confirm the presence of the short-range repulsion at any experimental condition (even at high salt concentration). A comparison between the experimental data and theoretical fits obtained from different theories has been performed in order to elucidate the nature of this non-DLVO repulsive force.
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| 31. |
- Valle-Delgado, J. J., et al.
(författare)
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Interaction forces between BSA layers adsorbed on silica surfaces measured with an atomic force microscope
- 2004
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 108:17, s. 5365-5371
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Tidskriftsartikel (refereegranskat)abstract
- The interaction forces between bovine serum albumin (BSA) layers adsorbed on silica surfaces have been measured using an atomic force microscope (AFM) in Conjunction with the colloid probe technique. Measurements of force-distance curves were made at different pH values and electrolyte concentrations (NaCl and CaCl2). The interaction at long range is dominated by electrical double-layer forces, while at short surface separations an additional repulsion due to the compression of the adsorbed protein layers appears. However, prior to this steric interaction, when the pH is above the isoelectric point of the protein and at high salt concentration, a non-DLVO repulsive interaction is observed. This behavior is explained if the presence of hydration forces in the system is assumed. Theoretical predictions including a hydration term in the DLVO theory fit the experimental results satisfactorily. The results presented in this article provide a direct confirmation that the AFM colloid probe technique can provide a useful way of directly quantifying the interaction of biological macromolecules.
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| 32. |
- Valle-Delgado, J. J., et al.
(författare)
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Interactions between bovine serum albumin layers adsorbed on different substrates measured with an atomic force microscope
- 2004
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 6:7, s. 1482-1486
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Tidskriftsartikel (refereegranskat)abstract
- By the aid of an atomic force microscope (AFM) and the colloid probe technique, the interaction forces between bovine serum albumin (BSA) layers adsorbed on different substrates (silica and polystyrene) have been measured directly as a function of pH and salt concentration. Electrostatic and steric forces dominate the interactions at low salt concentrations. At high salt concentrations, when electrostatic interactions are screened, a very strange behaviour is found as a function of pH. The behaviour around the i.e.p. of the protein is also very striking: the interaction is attractive at low salt concentration, but it is repulsive at high salt concentration. These results could be explained if the presence of hydration forces is assumed. Theoretical predictions including a hydration term in the DLVO theory fit the experimental results satisfactorily.
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| 33. |
- Valle-Delgado, J. J., et al.
(författare)
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Measurement of interactions between protein layers adsorbed on silica by atomic force microscopy
- 2004
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 16:26, s. 2383-2392
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Tidskriftsartikel (refereegranskat)abstract
- The present work, using an atomic force microscope and the colloid probe technique, investigates the interaction forces between bovine serum albumin (BSA) layers and between apoferritin layers adsorbed on silica surfaces. The measurements have been carried out in an aqueous medium at different pH values and NaCl concentrations. Similar behaviours have been found with both proteins. Electrostatic and steric forces dominate the interactions between the protein layers at low NaCl concentrations. However, a very strange behaviour is found as a function of pH at high NaCl concentrations. The results obtained under these conditions could be explained if the presence of hydration forces in these systems is assumed.
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| 34. |
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| 35. |
- van der Zwaan, Irès, et al.
(författare)
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Influence of particle diameter on aerosolization performance and release of budesonide loaded mesoporous silica particles
- 2024
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 200
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Tidskriftsartikel (refereegranskat)abstract
- The potential of micron-sized amorphous mesoporous silica particles as a novel controlled release drug delivery system for pulmonary administration has been investigated. Mesoporous silica formulations were demonstrated to provide a narrower particle size distribution and (spherical) shape uniformity compared to commercial micronized formulations, which is critical for repeatable and targeted aerosol delivery to the lungs. The release profiles of a well-known pulmonary drug loaded into mesoporous particles of different mean particle diameters (2.4, 3.9 and 6.3 µm) were analysed after aerosolization in a modified Andersen Cascade Impactor. Systematic control of the release rate of drug loaded into the particles was demonstrated in simulated lung fluid by variation of the mean particle diameter, as well as an enhanced release compared to a commercial micronized formulation. The mesoporous silica formulations all demonstrated an increased release rate of the loaded drug and moreover, under aerosolization from a commercial, low-cost dry powder inhaler (DPI) device, the formulations showed excellent performance, with low retainment and commercially viable fine particle fractions (FPFs). In addition, the measured median mass aerodynamic diameter (MMAD) of the different formulations (2.8, 4.1 and 6.2 µm) was shown to be tuneable with particle size, which can be helpful for targeting different regions in the lung. Together these results demonstrate that mesoporous silica formulations offer a promising novel alternative to current dry powder formulations for pulmonary drug delivery.
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| 36. |
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| 37. |
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| 38. |
- Zhou, Chunfang, et al.
(författare)
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Targeted Photodynamic Therapy with a Folate/Sensitizer Assembly Produced from Mesoporous Silica
- 2017
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Ingår i: Chemistry - A European Journal. - : Wiley-VCH Verlagsgesellschaft. - 0947-6539 .- 1521-3765. ; 23:32, s. 7672-7676
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Tidskriftsartikel (refereegranskat)abstract
- 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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