Jarno Salonen

University of Turku, Turku, Province of Western Finland, Finland

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Publications (163)600.82 Total impact

  • Biomaterials 01/2015; · 8.31 Impact Factor
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    ABSTRACT: A hybrid nanocomposite comprised by porous silicon nanoparticles and a stimuli responsive polymeric material, polyethylene glycol-block-poly(L-histidine), is spontaneously formed by nanoprecipitation in a flow-focusing microfluidic chip. The nanocomposite presents a novel hybrid compound micelle structure with a great robustness for therapeutic applications. Therefore, the nanocomposite is developed and tested as a “smart” multistage drug delivery system (MDDS) in response to some of the current problems that cancer treatment presents. Based on the stimuli-responsive behavior of the nanocomposite, a chemotherapeutic agent is successfully loaded into the nanosystem and released upon changes in the pH-values. The nanocomposite demonstrates enhanced stability in plasma, narrow size distribution, improved surface smoothness, and high cytocompatibility. Furthermore, the nanocomposite presents reduced nanoparticle internalization by phagocytic macrophage cells and pH-dependent cell growth inhibition capacity. Overall, the developed hybrid nanocomposite shows very promising features for its further development as a “smart” pH-responsive MDDS.
    Advanced Functional Materials 01/2015; · 10.44 Impact Factor
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    ABSTRACT: An advanced nanocomposite consisting of an encapsulated porous silicon (PSi) nanoparticle and an acid-degradable acetalated dextran (AcDX) matrix (nano-in-nano), was efficiently fabricated by a one-step microfluidic self-assembly approach. The obtained nano-in-nano PSi@AcDX composites showed improved surface smoothness, homogeneous size distribution, and considerably enhanced cytocompatibility. Furthermore, multiple drugs with different physicochemical properties have been simultaneously loaded into the nanocomposites with a ratiometric control. The release kinetics of all the payloads was predominantly controlled by the decomposition rate of the outer AcDX matrix. To facilitate the intracellular drug delivery, a nona-arginine cell-penetrating peptide (CPP) was chemically conjugated onto the surface of the nanocomposites by oxime click chemistry. Taking advantage of the significantly improved cell uptake, the proliferation of two breast cancer cell lines was markedly inhibited by the CPP-functionalized multidrug-loaded nanocomposites. Overall, this nano-in-nano PSi@polymer composite prepared by the microfluidic self-assembly approach is a universal platform for nanoparticles encapsulation and precisely controlled combination chemotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Biomaterials 01/2015; 39(42):249–259. · 8.31 Impact Factor
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    ABSTRACT: The aim of the research was to verify that electrospraying of piroxicam yielded a new polymorphic form of this drug. In the experiments, piroxicam was dissolved in chloroform and the solution was atomised electrostatically. Subsequently, the charged droplets were neutralised and dried. The solid drug particles were collected and analysed by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, high performance liquid chromatography, and infrared and Raman spectroscopy. The X-ray diffractogram measured for the electrosprayed piroxicam particles did not match with any of the known piroxicam crystal structures (Cambridge Crystallographic Data Centre). The variable temperature X-ray diffraction showed that the structure recrystallised completely into piroxicam polymorphic formI during heating. No degradation products or solvate removal were detected by high performance liquid chromatography and thermal analysis. The infrared and Raman spectra of the electrosprayed piroxicam were compared to those of formI, and some notable differences in the peak positions, shapes and intensities were detected. The results indicate that electrospraying leads to piroxicam crystallisation in a currently unknown polymorphic form. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmaceutics and Biopharmaceutics 01/2015; 81(1):182–189. · 4.25 Impact Factor
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    ABSTRACT: Abstract Context: Electrospraying was used in drug particle production. Objective: The aim of the research was to evaluate the possibilities to produce drug particles with desired pharmaceutical properties by electrospraying. In particular, the effect of drying pressure on particle properties was studied. Materials and methods: A poorly water soluble model drug (budesonide) was dissolved in chloroform, and the solution was atomized by electrospraying. Following this, the charged droplets were neutralized and dried in a drying chamber. The pressure in the drying chamber was varied. The dried particles were collected and analyzed. Results: The pressure reduction had a slight impact on particle size distribution. The particles produced in reduced pressure turned out to be notably more porous than the particles produced in atmospheric pressure. The pressure reduction also affects the degree of crystallinity of the product. The dissolution of the particles produced in reduced pressures was faster to a certain extent than that of the particles produced in atmospheric pressure. Discussion and conclusions: A setup for electrospraying materials in a reduced pressure was presented. The pressure reduction had a notable impact on particle morphology. The possibilities to tailor the particle properties during electrospraying were studied.
    Drug Development and Industrial Pharmacy 01/2015; 41(1):116-123. · 2.01 Impact Factor
  • Nano Research 01/2015; · 6.96 Impact Factor
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    ABSTRACT: Two limestones and two solid wastes were tested as adsorbents for chloride and sulphate ion removal from synthetic and real alkaline process mining water. The composition and surface structure of the adsorbents were analysed by ED-XRF, XRD, SEM and MIR spectroscopy and the nitrogen adsorption method. The optimal adsorption time and amount of adsorbent were determined by batch analysis with an anion concentration of 20 mg/L. In synthetic solution adsorbents removed 99% of SO42− and 96% of Cl− and in real process water the removal rate was 85% and 74% for SO42− and Cl−, respectively. It was found that equilibrium could successfully be fitted to the Langmuir, Toth and BiLangmuir adsorption isotherms.
    Chemical Engineering Journal 01/2015; 259:364–371. · 4.06 Impact Factor
  • ACS Applied Materials & Interfaces 01/2015; · 5.90 Impact Factor
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    ABSTRACT: Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism. Here, we report on effects of isoflavones against C. pneumoniae and C. trachomatis and describe buccal permeability and initial formulation development for biochanin A. Biochanin A was the most potent Chlamydia growth inhibitor among the studied isoflavones, with an IC50 = 12 µM on C. pneumoniae inclusion counts and 6.5 µM on infectious progeny production, both determined by immunofluorescent staining of infected epithelial cell cultures. Encouraged by the permeation of biochanin A across porcine buccal mucosa without detectable metabolism, oromucosal film formulations were designed and prepared by a solvent casting method. The film formulations showed improved dissolution rate of biochanin A compared to powder or a physical mixture, presumably due to the solubilizing effect of hydrophilic additives and presence of biochanin A in amorphous state. In summary, biochanin A is a potent inhibitor of Chlamydia spp., and the in vitro dissolution results support the use of a buccal formulation to potentially improve its bioavailability in antichlamydial or other pharmaceutical applications.
    PLoS ONE 12/2014; 9(12):e115115. · 3.53 Impact Factor
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    ABSTRACT: This study reports the use of variants of coherent anti-Stokes Raman scattering (CARS) microscopy as a novel method for improved physicochemical characterization of drug loaded silica particles. Ordered mesoporous silica is a biomaterial that can be loaded to carry a number of biochemicals including poorly water-soluble drugs by allowing the incorporation of drug into nanometer-sized pores. In this work, we qualitatively characterized the loading of two poorly water-soluble model drugs, itraconazole and griseofulvin, in MCM-41 silica microparticles using the novel approach of CARS microscopy, which has advantages over other analytical approaches used to date and is nondestructive, rapid, label-free, confocal and has chemical and physical specificity. We investigated the effect of two solvent-based loading methods, namely immersion and rotary evaporation, as well as microparticle size, on the three dimensional (3D) distribution of the two loaded drugs. Additionally, we used hyperspectral CARS microscopy to confirm the amorphous nature of the loaded drugs. Z-stacked CARS microscopy suggested the drug, but not loading method or particle size range, affected the 3D drug distribution. Hyperspectral CARS confirmed that the drug loaded in the MCM-41 silica microparticles was in an amorphous form. Our results show that CARS microscopy and hyperspectral CARS microscopy can be used to provide further insights into the structural nature of loaded mesoporous silica microparticles as biomaterials.
    Acta Biomaterialia 11/2014; 10(11):4870–4877. · 5.68 Impact Factor
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    ABSTRACT: The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is the emerging need for developing biopolymer-based composites capable of actively promote cellular proliferation and reconstitute the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan (CHI) and a mixture of chondroitin sulfate/hyaluronic acid (CS/HA), and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behaviour of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications.
    European Journal of Pharmaceutics and Biopharmaceutics 10/2014; 88(3):635–642. · 4.25 Impact Factor
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    ABSTRACT: Abstract Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases.
    Biomaterials 09/2014; 35(29):8394–8405. · 8.31 Impact Factor
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    ABSTRACT: Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1.
    Biomaterials 08/2014; · 8.31 Impact Factor
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    ABSTRACT: Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA(+)) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA(+) nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi-HA(+) relies on the capability of the conjugated HA(+) to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA(+)-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery.
    Nanoscale 07/2014; 6(11):10377–10387. · 6.74 Impact Factor
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    ABSTRACT: Nanoparticles (NPs) have been suggested for immunotherapy applications in order to optimize the delivery of immuno-stimulative or -suppressive molecules. However, low attention towards the impact of the NPs' physicochemical properties has presented a major hurdle for developing efficient immunotherapeutic agents. Here, the effects of porous silicon (PSi) NPs with different surface chemistries were evaluated on human monocyte-derived dendritic cells (MDDCs) and lymphocytes in order to highlight the importance of the NPs selection in immuno-stimulative or -suppressive treatment. Although all the PSi NPs showed high biocompatibility, only thermally oxidized PSi (TOPSi) and thermally hydrocarbonized PSi (THCPSi) NPs were able to induce very high rate of immunoactivation by enhancing the expression of surface co-stimulatory markers of the MDDCs (CD80, CD83, CD86, and HLA-DR), inducing T-cell proliferation, and also the secretion of interleukins (IL-1β, IL-4, IL-6, IL-10, IL-12, IFN-γ, and TNF-α). These results indicated a balanced increase in the secretion of Th1, Th2, and Treg cytokines. Moreover, undecylenic acid functionalized THCPSi, as well as poly(methyl vinyl ether-alt-maleic acid) conjugated to (3-aminopropyl)triethoxysilane functionalized thermally carbonized PSi and polyethyleneimine conjugated undecylenic acid functionalized THCPSi NPs showed moderate immunoactivation due to the mild increase in the above-mentioned markers. By contrast, thermally carbonized PSi (TCPSi) and (3-aminopropyl)triethoxysilane functionalized TCPSi NPs did not induce any immunological responses, suggesting that their application could be in the delivery of immunosuppressive molecules. Overall, our findings suggest all the NPs containing more nitrogen or oxygen on the outermost backbone layer have lower immunostimulatory effect than NPs with higher C-H structures on the surface.
    Biomaterials 07/2014; 35(33):9224–9235. · 8.31 Impact Factor
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    ABSTRACT: Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi–HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi–HA+ relies on the capability of the conjugated HA+ to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA+-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery.
    Nanoscale 07/2014; · 6.74 Impact Factor
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    ABSTRACT: The use of nanoparticle carriers for sustained release of cytotoxic drugs in cancer therapy can result in fewer adverse effects and can thus be of great benefit for the patient. Recently, a novel nanocomposite, prepared by the encapsulation of THCPSi nanoparticles within solid lipids (SLN), was developed and characterized as a promising drug delivery carrier in vitro. The present study describes the in vivo evaluation of unmodified THCPSi-nanoparticles and THCPSi-solid lipid nanocomposites (THCPSi-SLNCs) as potential drug delivery carriers for cancer therapy by using 18F-radiolabeling for the detection of the particle biodistribution in mice. Passive tumor targeting of 18F-THCPSis and 18F-THCPSi-SLNCs by the enhanced permeation and retention (EPR) effect was investigated in a murine breast cancer model. Encapsulation of THCPSi nanoparticles with solid lipids improved their accumulation into tumors at 7-week time-point (tumour-to-liver ratio 0.10 ± 0.08 and 0.24 ± 0.09% for 18F-THCPSis and 18F-THCPSi-SLNCs, respectively).
    Molecular Pharmaceutics 06/2014; 11(8):2876–2886. · 4.57 Impact Factor
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    ABSTRACT: Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 06/2014; · 2.61 Impact Factor
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    ABSTRACT: The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the bilayer polymer-conjugated NPs, the cellular trafficking and endosomal escape were significantly increased in both MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P) NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the system and preserves the endosomal escape properties via proton sponge mechanism of the free available amine groups located inside the hyper-branched PEI layer. Moreover, the double layer protection not only controlled the aggregation of the NPs and reduced the toxicity, but also sustained the drug release of an anticancer drug, methotrexate, with further improved cytotoxicity profile of the drug-loaded particles. These results provide a proof-of-concept evidence that such zwitterionic polymer-based PSi nanocomposites can be extensively used as a promising candidate for cytosolic drug delivery.
    Biomaterials 06/2014; 35(26):7488–7500. · 8.31 Impact Factor
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    ABSTRACT: Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (Papp) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane.
    Biomaterials 05/2014; 35(25):7172–7179. · 8.31 Impact Factor

Publication Stats

2k Citations
600.82 Total Impact Points

Institutions

  • 1996–2015
    • University of Turku
      • • Department of Physics and Astronomy
      • • Department of Physiatrics
      Turku, Province of Western Finland, Finland
  • 2014
    • Hospital Regional Universitario de Málaga
      Málaga, Andalusia, Spain
  • 2007–2014
    • University of Helsinki
      • • Division of Pharmaceutical Technology
      • • Department of Chemistry
      Helsinki, Southern Finland Province, Finland
  • 2013
    • Åbo Akademi University
      Turku, Province of Western Finland, Finland
  • 2012
    • University of Porto
      • Departamento de Química e Bioquímica
      Porto, Distrito do Porto, Portugal
  • 2010–2012
    • University of Eastern Finland
      • • School of Pharmacy
      • • Department of Physics and Mathematics
      Kuopio, Province of Eastern Finland, Finland
  • 2008
    • Japan Fine Ceramics Center
      Nagoya, Aichi, Japan