| 1. |
- Albèr, Cathrine, et al.
(author)
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Effects of water gradients and use of urea on skin ultrastructure evaluated by confocal Raman microspectroscopy
- 2013
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In: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier. - 0005-2736 .- 1879-2642 .- 0006-3002. ; 1828:11, s. 2470-2478
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Journal article (peer-reviewed)abstract
- The rather thin outermost layer of the mammalian skin, stratum corneum (SC), is a complex biomembrane which separates the water rich inside of the body from the dry outside. The skin surface can be exposed to rather extreme variations in ambient conditions (e.g. water activity, temperature and pH), with potential effects on the barrier function. Increased understanding of how the barrier is affected by such changes is highly relevant for regulation of transdermal uptake of exogenous chemicals. In the present study we investigate the effect of hydration and the use of a well-known humectant, urea, on skin barrier ultrastructure by means of confocal Raman microspectroscopy. We also perform dynamic vapor sorption (DVS) microbalance measurements to examine the water uptake capacity of SC pretreated with urea. Based on novel Raman images, constructed from 2D spectral maps, we can distinguish large water inclusions within the skin membrane exceeding the size of fully hydrated corneocytes. We show that these inclusions contain water with spectral properties similar to that of bulk water. The results furthermore show that the ambient water activity has an important impact on the formation of these water inclusions as well as on the hydration profile across the membrane. Urea significantly increases the water uptake when present in skin, as compared to skin without urea, and it promotes formation of larger water inclusions in the tissue. The results confirm that urea can be used as a humectant to increase skin hydration.
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| 2. |
- Björklund, Sebastian, et al.
(author)
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A calorimetric method to determine water activity
- 2011
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In: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 82:11
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Journal article (peer-reviewed)abstract
- A calorimetric method to determine water activity covering the full range of the water activity scale is presented. A dry stream of nitrogen gas is passed either over the solution whose activity should be determined or left dry before it is saturated by bubbling through water in an isothermal calorimeter. The unknown activity is in principle determined by comparing the thermal power of vaporization related to the gas stream with unknown activity to that with zero activity. Except for three minor corrections (for pressure drop, non-perfect humidification, and evaporative cooling) the unknown water activity is calculated solely based on the water activity end-points zero and unity. Thus, there is no need for calibration with references with known water activities. The method has been evaluated at 30 °C by measuring the water activity of seven aqueous sodium chloride solutions ranging from 0.1 mol kg−1 to 3 mol kg−1 and seven saturated aqueous salt solutions (LiCl, MgCl2, NaBr, NaCl, KCl, KNO3, and K2SO4) with known water activities. The performance of the method was adequate over the complete water activity scale. At high water activities the performance was excellent, which is encouraging as many other methods used for water activity determination have limited performance at high water activities.
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| 3. |
- Björklund, Sebastian, et al.
(author)
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A water gradient can be used to regulate drug transport across skin
- 2010
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In: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 143:2, s. 191-200
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Journal article (peer-reviewed)abstract
- At normal conditions there is a substantial water gradient over the skin as it separates the water-rich inside of the body from the dry outside. This leads to a variation in the degree of hydration from the inside to the outside of skin and changes in this gradient may affect its structure and function. In this study we raise the question: How do changes in the water gradient across skin affect its permeability? We approach this problem in novel diffusion experiments that permit strict control of the gradient in the chemical potential of water and hence well-defined boundary conditions. The results demonstrate that a water gradient can be used to regulate transport of drugs with different lipophilic characteristics across the skin barrier. It is shown that the transport of metronidazole (log Po/w=0.0) and methyl salicylate (log Po/w=2.5) across skin increases abruptly at low water gradients, corresponding to high degrees of skin hydration, and that this effect is reversible. This phenomenon is highly relevant to drug delivery applications due to its potential of temporarily open the skin barrier for transdermal drug delivery and subsequently close the barrier after treatment. Further, the results contribute to the understanding of the occlusion effect and indicate the boundary conditions of the water gradient needed to make use of this effect
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| 4. |
- Björklund, Sebastian, et al.
(author)
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Alcohols react with MCM-41 at room temperature and chemically modify mesoporous silica
- 2017
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Journal article (peer-reviewed)abstract
- Mesoporous silica has received much attention due to its well-defined structural order, high surface area, and tunable pore diameter. To successfully employ mesoporous silica for nanotechnology applications it is important to consider how it is influenced by solvent molecules due to the fact that most preparation procedures involve treatment in various solvents. In the present work we contribute to this important topic with new results on how MCM-41 is affected by a simple treatment in alcohol at room temperature. The effects of alcohol treatment are characterized by TGA, FTIR, and sorption calorimetry. The results are clear and show that treatment of MCM-41 in methanol, ethanol, propanol, butanol, pentanol, or octanol at room temperature introduces alkoxy groups that are covalently bound to the silica surface. It is shown that alcohol treated MCM-41 becomes more hydrophobic and that this effect is sequentially more prominent going from methanol to octanol. Chemical formation of alkoxy groups onto MCM-41 occurs both for calcined and hydroxylated MCM-41 and the alkoxy groups are hydrolytically unstable and can be replaced by silanol groups after exposure to water. The results are highly relevant for mesoporous silica applications that involve contact or treatment in protic solvents, which is very common.
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| 5. |
- Björklund, Sebastian, et al.
(author)
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Characterization of stratum corneum molecular dynamics by natural-abundance (13)c solid-state NMR.
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
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Journal article (peer-reviewed)abstract
- Despite the enormous potential for pharmaceutical applications, there is still a lack of understanding of the molecular details that can contribute to increased permeability of the stratum corneum (SC). To investigate the influence of hydration and heating on the SC, we record the natural-abundance (13)C signal of SC using polarization transfer solid-state NMR methods. Resonance lines from all major SC components are assigned. Comparison of the signal intensities obtained with the INEPT and CP pulse sequences gives information on the molecular dynamics of SC components. The majority of the lipids are rigid at 32°C, and those lipids co-exist with a small pool of mobile lipids. The ratio between mobile and rigid lipids increases with hydration. An abrupt change of keratin filament dynamics occurs at RH = 80-85%, from completely rigid to a structure with rigid backbone and mobile protruding terminals. Heating has a strong effect on the lipid mobility, but only a weak influence on the keratin filaments. The results provide novel molecular insight into how the SC constituents are affected by hydration and heating, and improve the understanding of enhanced SC permeability, which is associated with elevated temperatures and SC hydration.
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| 6. |
- Björklund, Sebastian, et al.
(author)
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Glycerol and urea can be used to increase skin permeability in reduced hydration conditions
- 2013
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In: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 5:50, s. 638-645
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Journal article (peer-reviewed)abstract
- The natural moisturizing factor (NMF) is a group of hygroscopic molecules that is naturally present in skin and protects from severe drying. Glycerol and urea are two examples of NMF components that are also used in skin care applications. In the present study, we investigate the influence of glycerol and urea on the permeability of a model drug (metronidazole, Mz) across excised pig skin membranes at different hydrating conditions. The degree of skin hydration is regulated by the gradient in water activity across the membrane, which in turn depends on the water activity of the formulation in contact with the skin membrane. Here, we determine the water activity of all formulations employed using an isothermal calorimetric method. Thus, the gradient in water activity is controlled by a novel experimental set-up with well-defined boundary conditions on both sides of the skin membrane. The results demonstrate that glycerol and urea can retain high steady state flux of Mz across skin membranes at dehydrating conditions, which otherwise would decrease the permeability due to dehydration. X-ray diffraction measurements are performed to give insight into the effects of glycerol and urea on SC molecular organization. The novel steady state flux results can be related to the observation that water, glycerol, and urea all affect the structural features of the SC molecular components in a similar manner.
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| 7. |
- Björklund, Sebastian, et al.
(author)
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Humidity scanning quartz crystal microbalance with dissipation monitoring setup for determination of sorption-desorption isotherms and rheological changes
- 2015
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In: Review of Scientific Instruments. - : American Institute of Physics (AIP). - 0034-6748 .- 1089-7623. ; 86:5
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Journal article (peer-reviewed)abstract
- A new method to determine water sorption-desorption isotherms with high resolution in the complete range of water activities (relative humidities) is presented. The method is based on quartz crystal microbalance with dissipation monitoring (QCM-D). The QCM-D is equipped with a humidity module in which the sample film is kept in air with controlled humidity. The experimental setup allows for continuous scanning of the relative humidity from either dry to humid conditions or vice versa. The amount of water sorbed or desorbed from the sample is determined from the resonance frequencies of the coated quartz sensor, via analysis of the overtone dependence. In addition, the method allows for characterization of hydration induced changes of the rheological properties from the dissipation data, which is closely connected to the viscoelasticity of the film. The accuracy of the humidity scanning setup is confirmed in control experiments. Sorption-desorption isotherms of pig gastric mucin and lysozyme, obtained by the new method, show good agreement with previous results. Finally, we show that the deposition technique used to coat the quartz sensor influences the QCM-D data and how this issue can be used to obtain further information on the effect of hydration. In particular, we demonstrate that spin-coating represents an attractive alternative to obtain sorption-desorption isotherms, while drop-coating provides additional information on changes of the rheological properties during hydration.
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| 8. |
- Björklund, Sebastian, et al.
(author)
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Hydration-Induced Phase Transitions in Surfactant and Lipid Films
- 2016
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In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:21, s. 5223-5232
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Journal article (peer-reviewed)abstract
- For several surfactant and lipid systems, it is crucial to understand how hydration influences the physical and chemical properties. When humidity changes, it affects the degree of hydration by adding or removing water molecules. In many cases, this process induces transitions between liquid crystalline phases. This phenomenon is of general interest for numerous applications simply because of the fact that humidity variations are ubiquitous. Of particular interest are hydration-induced phase transitions in amphiphilic films, which in many cases appear as the frontier toward a vapor phase with changing humidity. Considering this, it is important to characterize the film thickness needed for the formation of 3D liquid crystalline phases and the lyotropic phase behavior of this kind of film. In this work, we study this issue by employing a recently developed method based on the humidity scanning quartz crystal microbalance with dissipation monitoring (HS QCM-D), which enables continuous scanning of the film hydration. We investigate five surfactants films (DDAO, DTAC, CTAC, SDS, and n-octyl beta-D-glucoside) and one lipid film (monoolein) and show that HS QCM-D enables the fast characterization of hydration-induced phase transitions with small samples. Film thicknesses range from tens to hundreds of nanometers, and clear phase transitions are observed in all cases. It is shown that phase transitions in films occur at the same water activities as for corresponding bulk samples. This allows us to conclude that surfactant and lipid films, with a thickness of as low as 50 nm, are in fact assembled as 3D-structured liquid crystalline phases. Furthermore, liquid crystalline phases of surfactant films show liquidlike behavior, which decreases the accuracy of the absorbed water mass measurement. On the other hand, the monoolein lipid forms more rigid liquid crystalline films, allowing for an accurate determination of the water sorption isotherm, which is also true for the sorption isotherms corresponding to the solid surfactant phases.
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| 9. |
- Björklund, Sebastian
(author)
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Skin hydration - How water and osmolytes influence biophysical properties of stratum corneum
- 2013
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Doctoral thesis (other academic/artistic)abstract
- The outermost layer of skin (i.e., the stratum corneum, SC) is the interface that separates the water-rich inside of the body from the relatively dry external environment. SC forms an effective permeability barrier, which has to be overcome in transdermal drug delivery. Its function as a barrier for molecular diffusion depends on the SC molecular structure and phase behavior. Both structure and phase behavior may be altered, for example, by hydration or addition of other solutes, which affects the barrier properties. This thesis explores the interplay between molecular properties of SC components and the macroscopic properties of the SC membrane. We investigate the influence of hydration on SC permeability at steady state by using an in vitro set-up where the boundary conditions are controlled by the water activity in the solutions in contact with the skin membrane. Changes of macroscopic properties are rationalized by employing techniques that provide information on SC molecular organization and molecular dynamics. We show that SC hydration leads to increased SC permeability, which is attributed to a higher fraction of fluid SC molecular components with lower diffusional resistance. This can have implications, for example, in transdermal delivery applications where it is desirable to increase the amount of drug delivered across the skin barrier to reach therapeutic effect. We show that common so-called moisturizers, like glycerol and urea, can be used to retain high SC permeability under dehydrating conditions. This effect is ascribed to the capability of these small polar molecules to maintain the SC molecular properties in a state that is similar to a more hydrated SC membrane at reduced hydration conditions. This result provides a deeper understanding of the beneficial effect of moisturizers in treatment of dry skin conditions and challenges the view that moisturizers, like glycerol and urea, are beneficial for skin health by merely increasing the SC hydration.
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| 10. |
- Björklund, Sebastian, et al.
(author)
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Skin membrane electrical impedance properties under the influence of a varying water gradient
- 2013
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In: Biophysical Journal. - : Elsevier. - 0006-3495 .- 1542-0086. ; 104:12, s. 2639-2650
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Journal article (peer-reviewed)abstract
- The stratum corneum (SC) is an effective permeability barrier. One strategy to increase drug delivery across skin is to increase the hydration. A detailed description of how hydration affects skin permeability requires characterization of both macroscopic and molecular properties and how they respond to hydration. We explore this issue by performing impedance experiments on excised skin membranes in the frequency range 1 Hz to 0.2 MHz under the influence of a varying gradient in water activity (aw). Hydration/dehydration induces reversible changes of membrane resistance and effective capacitance. On average, the membrane resistance is 14 times lower and the effective capacitance is 1.5 times higher when the outermost SC membrane is exposed to hydrating conditions (aw ¼ 0.992), as compared to the case of more dehydrating conditions (aw ¼ 0.826). Molecular insight into the hydration effects on the SC components is provided by natural-abundance 13C polarization transfer solidstate NMR and x-ray diffraction under similar hydration conditions. Hydration has a significant effect on the dynamics of the keratin filament terminals and increases the interchain spacing of the filaments. The SC lipids are organized into lamellar structures with ~ 12.6 nm spacing and hexagonal hydrocarbon chain packing with mainly all-trans configuration of the acyl chains, irrespective of hydration state. Subtle changes in the dynamics of the lipids due to mobilization and incorporation of cholesterol and long-chain lipid species into the fluid lipid fraction is suggested to occur upon hydration, which can explain the changes of the impedance response. The results presented here provide information that is useful in explaining the effect of hydration on skin permeability.
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