Jarno Salonen

Harvard University, Cambridge, Massachusetts, United States

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Publications (204)757.36 Total impact

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    ABSTRACT: The new frontier in the treatment of chronic non-healing wounds is the use of micro- and nanoparticles to deliver drugs or growth factors into the wound. Here, we used platelet lysate (PL), a hemoderivative of platelets, consisting of a multifactorial cocktail of growth factors, to modify porous silicon (PSi) microparticles and assessed both in vitro and ex vivo the properties of the developed microsystem. PL-modified PSi was assessed for its potential to induce proliferation of fibroblasts. The wound closure-promoting properties of the microsystem were then assessed in an in vitro wound healing assay. Finally, the PL-modified PSi microparticles were evaluated in an ex vivo experiment over human skin. It was shown that PL-modified PSi microparticles were cytocompatible and enhanced the cell proliferation in different experimental settings. In addition, this microsystem promoted the closure of the gap between the fibroblast cells in the wound healing assay, in periods of time comparable with the positive control, and induced a proliferation and regeneration process onto the human skin in an ex vivo experiment. Overall, our results show that PL-modified PSi microparticles are suitable microsystems for further development towards applications in the treatment of chronic non-healing wounds.
    No preview · Article · Jan 2016 · ACS Applied Materials & Interfaces
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    ABSTRACT: Interfacial polymerization of uniform template-free nanostructures is very challenging since many factors play determinant roles in the final structure of the resulting nanoassemblies. Here, we present a single oxidative coupling method for the synthesis of different nanoshapes by addition or substitution of a methyl group on aniline monomers to freely alter the mechanism of monomer-topolymer conversion. Well-defined nanotubes, nanohollows and solid nanospheres are obtained from aniline, N-methylaniline, and 2-methylaniline polymerizations, respectively. We found out that the extent of hydrophobicity and protonation in mild acidic conditions determines the monomers’ arrangement in micelle or droplet form, their reactivity, and nucleation mechanism. These can subsequently affect the final morphology through a fusion process to form tubular structures, external flux of monomers to form nanohollows, and intradroplet oxidation to form solid nanospheres. Altered biological responses, such as cytocompatibility, redox response, hemocompatibility, and cell proliferation are also found to be dependent on the position of the methyl group in the nanostructures.
    No preview · Article · Dec 2015 · Chemistry of Materials
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    ABSTRACT: Hydrothermal carbonization of cellulose in the presence of the globular protein ovalbumin leads to the formation of nitrogen doped carbon aerogel with a fibrillar continuous carbon network. The protein plays here a double role: i) a natural source of nitrogen functionalities (2.1 wt. %) and ii) structural directing agent (SBET = 38 m2/g). The applicability in wastewater treatment, namely for heavy metal removal, was examined through adsorption of Cr(VI) and Pb(II) ion solely and in a mixed bicomponent aqueous solutions. This cellulose-based carbogel shows an enhanced ability to remove both Cr(VI) (~68 mg/g) and Pb(II) (~240 mg/g) from the targeted solutions in comparison to other carbon materials reported in the literature. The presence of competing ions showed little effect on the adsorption efficiency towards Cr(VI) and Pb(II).
    No preview · Article · Nov 2015 · ACS Applied Materials & Interfaces
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    ABSTRACT: The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDM™)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS) and subcutaneous rods (SR). The goal was to select an EVA grade with the optimal properties, namely vinyl acetate content, melting index, flexural modulus, for 3D printing of implantable prototypes with the drug incorporated within the entire matrix of the medical devices. Indomethacin was used as a model drug in this study. Out of the twelve tested grades of the EVA five were printable. One of them showed superior print quality and was further investigated by printing drug-loaded filaments, containing 5% and 15% indomethacin. The feedstock filaments were fabricated by hot-melt extrusion (HME) below the melting point of the drug substance and the IUS and SRs were successfully printed at the temperature above the melting point of the drug. As a result, the drug substance in the printed prototypes showed to be at least partly amorphous, while the drug in the corresponding HME filaments was crystalline. This difference affected the drug release profiles from the filaments and printed prototype products: faster release from the prototypes over 30days in the in vitro tests. To conclude, this study indicates that certain grades of EVA were applicable feedstock material for 3D printing to produce drug-loaded implantable prototypes.
    Full-text · Article · Nov 2015 · European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences
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    ABSTRACT: Nanotechnology based drug delivery systems are anticipated to overcome the persistent challenges in oral protein and peptide administration, and lead to the development of long awaited non-invasive therapies. Herein, an advanced single-step aerosol flow reactor based technology was used to develop a multifunctional site specific dual protein-drug delivery nanosystem. For this purpose, mucoadhesive porous silicon (PSi) nanoparticles encapsulated into a pH-responsive polymeric nanomatrix was developed for advanced oral type 2 diabetes mellitus therapy with an antidiabetic peptide, glucagon like peptide-1 (GLP-1), and the enzyme inhibitor, dipeptidyl peptidase-4 (DPP4). Chitosan surface modification inherited the mucoadhesiveness to the nanosystem which led to enhanced cellular interactions and increased cellular compatibility. An advanced aerosol flow reactor technology was used to encapsulate the chitosan modified nanoparticles into an enteric polymeric nanomatrix. The pH-sensitive polymeric matrix simultaneously prevented the gastric degradation of the encapsulated peptide and also preserved the mucoadhesive functionality of the chitosan-modified PSi nanoparticles in the harsh stomach environment. The multidrug loaded nanosystem showed augmented intestinal permeability of GLP-1, evaluated in an in vitro cell-based intestinal epithelium model, attributed to the permeation enhancer effect of chitosan and inhibition of GLP-1 degradation by the DPP4 inhibitor. The applied technology resulted in the development of a dual-drug delivery nanosystem that synergizes the antidiabetic effect of the loaded peptide and the enzyme inhibitor, thereby indicating high clinical potential of the system and preparation technique. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Nov 2015 · Biomaterials
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    ABSTRACT: Over the last decade, the potential of polymeric structures has been investigated to overcome many limitations related to nanosized drug carriers by modulating their toxicity, cellular interactions, stability and drug release kinetic. In this study, we have developed a successful nanocomposite consisting of undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with an anticancer drug, sorafenib, and surface conjugated with heptakis(6-amino-6-deoxy)-beta-cyclodextrin (HABCD) showed the impact of the surface polymeric functionalization on the physical and biological properties of the drug-loaded nanoparticles. Cytocompatibility studies showed that the UnTHCPSi-HABCD NPs were not toxic to breast cancer cells. HABCD also enhanced the suspensibility, and both the colloidal and plasma stability of the UnTHCPSi NPs. UnTHCPSi-HABCD NPs showed a significantly increased interaction with breast cancer cells compared to bare NPs and thereby sustained the drug release. Furthermore, the sorafenib-loaded UnTHCPSi-HABCD NPs efficiently inhibited the cell proliferation of the breast cancer cells.
    No preview · Article · Oct 2015 · ACS Applied Materials & Interfaces
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    ABSTRACT: The hydrothermal carbonization (HTC) technique has shown a great ability in the synthesis of carbon materials with special properties for a wide range of different applications. Here, a hypersaline salt mixture (LiCl–ZnCl2) combined with hydrothermal carbonization was applied in order to obtain sulfur containing micro- and mesoporous (0.3–40 nm) monolithic carbons with high surface areas (400–550 m2 g−1) and well developed porosity (0.4–1.2 cm3 g−1). Fructose was used as a carbon source and sulfur was introduced in an aromatic configuration as 2-thiophenecarboxaldehyde. The resulting carbon materials showed a promising removal capacity (qe = 0.3 mmol g−1) towards methylene blue and the adsorption followed the Sips isotherm independent of the pH. Intraparticle diffusion appeared to control the adsorption kinetics. Carbon materials could be easily regenerated with simple ethanol washing. The dye pollutant could be completely desorbed from the adsorbent's surface, while the adsorbent still maintained removal efficiency of above 90% during three cycles.
    No preview · Article · Oct 2015 · Green Chemistry

  • No preview · Article · Oct 2015 · ECS Transactions
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    ABSTRACT: Dissolution rates of two very pure limestone samples were measured experimentally by means of the pH-stat method under conditions where mechanical stirring did not affect the rates considerably. The experimental results were modeled mathematically by considering the surface areas of the particles changing dynamically through the reaction; moreover, a surface factor was introduced in order to account for the nonsphericity of the particles. The surface areas were measured by means of gas adsorption and by particle size distribution (laser diffraction). Liquid-phase concentrations were measured by inductively coupled plasma optical emission spectrometry, and surface compositions were measured by X-ray spectroscopy. Furthermore, scanning electron microscope images of the samples are presented. Subsequently, an optimization model of a scrubber was developed by using the intrinsic parameters of the samples, which were determined experimentally. The optimization results indicate that up to 34-50% of the power required for milling can be saved by milling to a coarser particle size than the commonly used size of 44 μm, depending on the sample type. The present model of the lab-scale experimental study and the optimization model can be employed to estimate the actual impact that using different types of raw material would have in the operation of a wet flue gas desulfurization scrubber.
    No preview · Article · Sep 2015 · Industrial & Engineering Chemistry Research
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    ABSTRACT: In this study, thermally hydrocarbonised porous silicon nanoparticles (THCpSiNPs) capped with polyethylenimine (PEI) were fabricated, and their potential for small interfering RNA (siRNA) delivery was investigated in an in vitro glioblastoma model. PEI coating following siRNA loading enhanced the sustained release of siRNA, and suppressed burst release effects. The positively-charged surface improved the internalisation of the nanoparticles across the cell membrane. THCpSiNP-mediated siRNA delivery reduced mRNA expression of the MRP1 gene, linked to the resistence of glioblastoma to chemotherapy, by 63% and reduced MRP1-protein levels by 70%. MRP1 siRNA loaded nanoparticles did not induce cytotoxicity in glioblastoma cells, but markedly reduced cell proliferation. In summary, the results demonstrated that non-cytotoxic cationic THCpSiNPs are promising vehicles for therapeutic siRNA delivery.
    No preview · Article · Sep 2015
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    ABSTRACT: Multifunctional tailorable composite systems, specifically designed for orally dual-deliver of a peptide (glucagon-like peptide-1) and an enzymatic inhibitor (dipeptidyl peptidase 4 (DPP4)), were assembled through the microfluidics technique. Both drugs were co-loaded into these systems for a synergistic therapeutic effect. The systems were composed of chitosan and cell-penetrating peptide modified poly(lactide-co-glycolide) and porous silicon nanoparticles as nanomatrices, further encapsulated in an enteric hydroxypropylmethylcellulose acetylsuccinate polymer. The developed multifunctional systems were pH-sensitive, inherited by the enteric polymer, enabling the release of the nanoparticles only in the simulated intestinal conditions. Moreover, the encapsulation into this polymer prevented the degradation of the nanoparticles’ modifications. These nanoparticles showed strong and higher interactions with the intestinal cells in comparison with the non-modified ones. The presence of DPP4 inhibitor enhanced the peptide permeability across intestinal cell monolayers. Overall, this is a promising platform for simultaneously deliver two drugs from a single formulation. Through this approach peptides are expected to increase their bioavailability and efficiency in vivo both by their specific release at the intestinal level and also by the reduced enzyme activity. The use of this platform, specifically in combination of the two antidiabetic drugs, has clinical potential for the therapy of type 2 diabetes mellitus.
    No preview · Article · Aug 2015 · ACS Nano
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    ABSTRACT: Limestones and their modifications from Nordkalk Corporation (Finland) flotation fines (FF) and filter sand (FS) as potential adsorbents for AMD treatment and wastewater purification from Cu, Fe, Zn and Ni ions were studied. Limestones were capable of binding significant amounts of Cu and Fe from synthetic AMD solutions and wastewater, while unmodified limestones were not good for Zn and Ni removal. Two methods of surface area modification were suggested. The first one with 2 M solution of NaCl and the second one with wastewater from Norilsk Nickel Harjavalta. The structure of materials and their surface area were characterized by SEM, EDX, MIR spectroscopy and nitrogen adsorption methods. Optimal amount of adsorbents for different model and real solutions was found. Adsorption kinetics showed that the adsorption equilibrium was reached within approximately 8 h. The kinetic data fits to a pseudo second order model with correlation coefficients greater than 0.999. The adsorption capacity was the highest at solution pH range of 6–7. Langmuir, Toth and Sips models were used to fit the adsorption isotherms. Based on the parameters calculated from models, the adsorption capacity decreased in the order of Cu > Fe > Zn > Ni for FF and Fe > Cu > Zn > Ni for FS. The research showed that the proposed modified limestones can be successfully used for AMD neutralization and removal of Cu(II), Fe(III), Zn(II) and Ni(II).
    Full-text · Article · Aug 2015 · Ecological Engineering
  • Janne Peltonen · Matti Murtomaa · Jarno Salonen
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    ABSTRACT: A coaxial induction probe for measuring the charge, size and distance of a passing object is presented. Two different current signals were induced as an object passed the probes. The signals were integrated and Gaussian curves were fitted to the data. According to simulations done with Comsol Multiphysics, the charge, size and distance could be calculated from the amplitudes and widths of the curves. The system was simulated, built and calibrated. It was tested in powder measurements in a fluidized bed device.
    No preview · Article · Aug 2015 · Journal of Electrostatics
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    ABSTRACT: The oral bioavailability of a poorly water-soluble drug is often inadequate for the desired therapeutic effect. The bioavailability can be improved by enhancing the physicochemical properties of the drug (e.g. dissolution rate, permeation across the gastrointestinal tract). Another approach is drug shielding from the gastric metabolism, and targeted drug release to obtain optimal drug absorption. In this study, a poorly water-soluble model drug griseofulvin was encapsulated as disordered solid dispersions into Eudragit® L 100-55 enteric polymer micromatrix particles, which were produced by electrospraying. Similar micromatrix particles were also produced, with griseofulvin-loaded thermally oxidized mesoporous silicon (TOPSi) nanoparticles dispersed to the polymer micromatrices. The in vitro drug dissolution at pH 1.2 and 6.8, and permeation at pH 7.4 across Caco-2/HT29 cell monolayers from the micromatrix particles were investigated. The micromatrix particles were found to be gastro-resistant, while at pH 6.8 the griseofulvin was released very rapidly in a fast dissolving form. Compared to free griseofulvin, the griseofulvin permeability across the intestinal cell monolayers was greatly improved, particularly for the TOPSi doped micromatrix particles. The griseofulvin solid dispersions were stable during a storage for 6 months at accelerated conditions. Overall, the method developed here could prove as a useful oral drug delivery solution for improving the bioavailability of poorly water-soluble or otherwise problematic drugs.
    No preview · Article · Jul 2015 · Molecular Pharmaceutics
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    ABSTRACT: Peptides have long been recognized as a promising group of therapeutic substances to treat various diseases. Delivery systems for peptides have been under development since the discovery of insulin for the treatment of diabetes. The challenge of using peptides as drugs arises from their poor bioavailability resulting from the low permeability of biological membranes and their instability. Currently, subcutaneous injection is clinically the most common administration route for peptides. This route is cost-effective and suitable for self-administration, and the development of appropriate dosing equipment has made performing the repeated injections relatively easy; however, only few clinical subcutaneous peptide delivery systems provide sustained peptide release. As a result, frequent injections are needed, which may cause discomfort and additional risks resulting from a poor administration technique. Controlled peptide delivery systems, able to provide required therapeutic plasma concentrations over an extended period, are needed to increase peptide safety and patient compliancy. In this review, we summarize the current peptidergic drugs, future developments, and parenteral peptide delivery systems. Special emphasis is given to porous silicon, a novel material in peptide delivery. Biodegradable and biocompatible porous silicon possesses some unique properties, such as the ability to carry exceptional high peptide payloads and to modify peptide release extensively. We have successfully developed porous silicon as a carrier material for improved parenteral peptide delivery. Nanotechnology, with its different delivery systems, will enable better use of peptides in several therapeutic applications in the near future. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
    Full-text · Article · Jul 2015 · Pharmacological reviews
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    Janne Peltonen · Matti Murtomaa · Jarno Salonen
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    ABSTRACT: A new kind of probe for measuring the charge, size and distance of a passing object has been simulated, built and calibrated previously [1]. The probe consisted of a circular inner sensor, surrounded by an insulator, and an outer ring. In this geometry, two different current signals were induced to the sensors as a charged object passed by. By integrating the signals over time, the induced charge could be obtained. The charge, size and distance of the object were calculated from the amplitudes and widths of Gaussian curves fitted to the data. However, calibrating the new probe with charged spheres pointed out some weaknesses. Unlike in the simulations made with Comsol Multiphysics, the speed of the object could not be calculated since the Gaussian peak width data proved to be poor. Moreover, all the simulations and testing were done with objects passing the axis of the probe. If the object passed the probe asymmetrically, the calculations gave false results. According to the new simulations, the poor Gaussian width ratio, which is required for more reliable calculation, can be improved by using a larger outer ring. The displacement problem can be solved if the outer ring is split vertically into two adjacent parts. This way the outer probe tells how much the object is aside from the center. We present simulation results obtained by varying the probe geometry.
    Full-text · Conference Paper · Jun 2015
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    ABSTRACT: Biocompatible, multifunctional, stimuli-responsive and high drug loading capacity are key factors for the new generation of drug delivery platforms. However, it is extremely challenging to create such a platform that inherits all these advanced properties in a single carrier. Herein, porous silicon nanoparticles (PSi NPs) and giant liposomes were assembled on a microfluidic chip as an advanced nano-in-micro platform (PSi NPs@giant liposomes), which can co-load and co-deliver hydrophilic and hydrophobic drugs combined with synthesized DNA nanostructures, short gold nanorods and magnetic nanoparticles. The PSi NPs@giant liposomes with photothermal and magnetic responsiveness showed good biocompatibility, high loading capacity and controllable release. The hydrophilic thermal oxidized PSi NPs encapsulate hydrophobic therapeutics within the hydrophilic core of the giant liposomes, endowing high therapeutics loading capacity with tuneable ratio and controllable release. We demonstrate that the DAO-E A DNA nanostructures have synergism with drugs and importantly they contribute to the significant enhancement of cell death to doxorubicin-resistant MCF-7/DOX cells, overcoming the multidrug resistance in the cancer cells. Therefore, the PSi NPs@giant liposomes nano-in-micro platform hold great potential for a cocktail delivery of drugs and DNA nanostructures for effective cancer therapy, controllable drug release with tuneable therapeutics ratio, and both photothermal and magnetic dual-responsiveness.
    No preview · Article · Jun 2015 · Advanced Functional Materials
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    ABSTRACT: Background Stricter SO2 emission regulations for power plants and maritime transport encourage for a better understanding of the phenomena involved in wet flue gas desulfurization (WFGD) where limestone dissolution is regarded as one of the rate determining steps.ResultsThe dissolution kinetics of two limestone samples was studied in the industrially most relevant pH range 2.4-6. Dissolution experiments were performed under a regime where mechanical stirring did not affect the dissolution rate significantly. Furthermore, a mathematical model was developed by coupling mass transfer and chemical reaction on the surface along the whole range of pH, an analogy of the well-known Langmuir isotherm was applied. The results show that it is possible to accurately model the whole pH range, between 99.1-99.5% degree of explanation and low relative standard errors ≤2%.Conclusion Limestone dissolution was successfully modeled by implementing surface areas measured by physisorption which were also compared to particle size distribution (PSD) measurements. Selected liquid-phase concentrations were measured by means of inductively coupled plasma optical emission spectrometry (ICP-OES) in order to support the proposed mechanism. The samples were characterized by X-ray fluorescence (XRF), X-ray spectroscopy (EDX) and scanning electron microscopy (SEM). A wide range of studies presented in the literature are also described.
    No preview · Article · Jun 2015 · Journal of Chemical Technology & Biotechnology
  • Matti Murtomaa · Janne Peltonen · Jarno Salonen
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    ABSTRACT: A new one-step technique to measure the effect of ambient humidity on powder resistivity has been previously presented. In this article, we provide more experimental data obtained with five different powders. One-step measurements and traditional multi-step measurements were performed. Also, additional measurements were performed using standard resistivity cell. Results were compared and it could be concluded that the new technique provided meaningful results although significant hysteresis was observed during humidification and drying cycles. Finally, charging of the powder was also measured and it was noticed that it decreases with decreasing resistivity and increasing humidity.
    No preview · Article · May 2015 · Journal of Electrostatics
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    ABSTRACT: Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody (Ab) were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi (Un-Ab) NPs at concentrations lower than 200 μg·mL−1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.
    Full-text · Article · May 2015 · Nano Research

Publication Stats

4k Citations
757.36 Total Impact Points

Institutions

  • 2015
    • Harvard University
      • Department of Physics
      Cambridge, Massachusetts, United States
  • 1996-2015
    • University of Turku
      • • Department of Physics and Astronomy
      • • Department of Physiatrics
      Turku, Varsinais-Suomi, Finland
  • 2014
    • Hospital Regional Universitario de Málaga
      Málaga, Andalusia, Spain
  • 2011
    • University of Helsinki
      • Division of Pharmaceutical Technology
      Helsinki, Province of Southern Finland, Finland