Ändra sökning
Avgränsa sökresultatet
1 - 16 av 16
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Björn, Camilla
    et al.
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. Pergamum AB, Sweden; University of Gothenburg, Sweden.
    Mahlapuu, Margit
    Pergamum AB, Sweden; University of Gothenburg, Sweden.
    Mattsby-Baltzer, Inger
    University of Gothenburg, Sweden.
    Håkansson, Joakim
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. Pergamum AB, Sweden.
    Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r2016Ingår i: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 81, s. 21-28Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing ≥99% of microorganisms in vitro, was in the range of 3-50 μg/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-α) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400 μg/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections.

  • 2.
    Boge, Lukas
    et al.
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science. Chalmers University of Technology, Sweden.
    Bysell, Helena
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science.
    Ringstad, Lovisa
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science.
    Wennman, David
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Process Development, Analys och fastfas.
    Umerska, Anita
    University of Angers, France.
    Cassisa, Viviane
    CHU Angers, France.
    Eriksson, Jonny
    Uppsala University, Sweden.
    Joly-Guillou, Marie-Laure
    CHU Angers, France.
    Edwards, Katarina
    Uppsala University, Sweden.
    Andersson, Martin
    Chalmers University of Technology, Sweden.
    Lipid-based liquid crystals as carriers for antimicrobial peptides: Phase behavior and antimicrobial effect2016Ingår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 32, nr 17, s. 4217-4228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, ζ-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.

  • 3.
    Christensen, Gustav
    et al.
    University of Tübingen, Germany.
    Urimi, Dileep
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel. University of Iceland, Iceland.
    Lorenzo‐Soler, Laura
    University of Iceland, Iceland.
    Schipper, Nicolaas
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel.
    Paquet-Durand, François
    University of Tübingen, Germany.
    Ocular permeability, intraocular biodistribution of lipid nanocapsule formulation intended for retinal drug delivery2023Ingår i: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 187, s. 175-183Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recently, cGMP analogues have been investigated for the treatment of inherited retinal degenerations (IRD) using intravitreal injections. However, higher vitreous elimination rates limit the possibility to treat the retina with small molecule drugs. Here, we investigated the potential of lipid nanocapsules (LNCs) as vehicles to reduce clearance and prolong the delivery of cGMP analogue, CN03 to the retinal photoreceptors. Initially LNCs were investigated for both topical/periocular and intravitreal administration routes. While LNC-mediated drug permeation through the cornea proved to be too low for clinical applications, intravitreal application showed significant promise. Intravitreally administered LNCs containing fluorescent tracer in ex vivo porcine eyes showed complete intravitreal dispersal within 24 h. Ocular bio-distribution on histological sections showed that around 10 % of the LNCs had reached the retina, and 40 % accumulated in the ciliary body. For comparison, we used fluorescently labeled liposomes and these showed a different intraocular distribution with 48 % accumulated in the retina, and almost none were in the ciliary body. LNCs were then tested in retinal explants prepared from wild-type (WT) and rd1 mouse. In WT retina LNCs showed no significant toxic effects up to a concentration of 5 mg/mL. In rd1 retina, the LNC/CN03 formulation protected rd1 photoreceptors with similar efficacy to that of free CN03, demonstrating the usefulness of LNC/CN03 formulation in the treatment of IRD. Overall, our results indicate the suitability of LNCs for intraocular administration and drug delivery to both the retina and the ciliary body. © 2023 The Author(s)

  • 4.
    Colombo, Stefan
    et al.
    Uppsala University, Sweden.
    Brisander, Magnus
    XSpray Microparticles AB, Sweden.
    Haglöf, Jakob
    Uppsala University, Sweden.
    Sjövall, Peter
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Andersson, Per
    XSpray Microparticles AB, Sweden.
    Østergaard, Jesper
    University of Copenhagen, Denmark.
    Malmsten, Martin
    Uppsala University, Sweden.
    Matrix effects in nilotinib formulations with pH-responsive polymer produced by carbon dioxide-mediated precipitation2015Ingår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 494, nr 1, s. 205-217, artikel-id 15114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Factors determining the pH-controlled dissolution kinetics of nilotinib formulations with the pH-titrable polymer hydroxypropyl methylcellulose phthalate, obtained by carbon dioxide-mediated precipitation, were mechanistically examined in acid and neutral environment. The matrix effect, modulating the drug dissolution, was characterized with a battery of physicochemical methodologies, including ToF-SIMS for surface composition, SAXS/WAXS and modulated DSC for crystallization characterization, and simultaneous UV-imaging and Raman spectroscopy for monitoring the dissolution process in detail. The hybrid particle formulations investigated consisted of amorphous nilotinib embedded in a polymer matrix in single continuous phase, displaying extended retained amorphicity also under wet conditions. It was demonstrated by Raman and FTIR spectroscopy that the efficient drug dispersion and amorphization in the polymer matrix were mediated by hydrogen bonding between the drug and the phthalate groups on the polymer. Simultaneous Raman and UV-imaging studies of the effect of drug load on the swelling and dissolution of the polymer matrix revealed that high nilotinib load prevented matrix swelling on passage from acid to neutral pH, thereby preventing re-precipitation and re-crystallization of incorporated nilotinib. These findings provide a mechanistic foundation of formulation development of nilotinib and other protein kinase inhibitors, which are now witnessing an intense therapeutic and industrial attention due to the difficulty in formulating these compounds so that efficient oral bioavailability is reached.

  • 5.
    Janosik, Tomasz
    et al.
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel.
    Berg, Robert
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel.
    Chemistry of Silepins and their Analogs Containing Group 14 Elements2021Ingår i: ARKIVOC, ISSN 1551-7004, E-ISSN 1551-7012, Vol. 2020, nr 7, s. 379-400Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The chemistry of silepins and related seven-membered heterocycles containing group 14 elements is reviewed. 

  • 6.
    Kuna, V K
    et al.
    University of Gothenburg, Sweden.
    Padma, A M
    University of Gothenburg, Sweden.
    Håkansson, Joakim
    RISE - Research Institutes of Sweden, Biovetenskap och material, Kemi och material.
    Nygren, J
    TATAA Biocenter, Sweden.
    Sjöback, R
    TATAA Biocenter, Sweden.
    Petronis, Sarunas
    RISE - Research Institutes of Sweden, Biovetenskap och material, Kemi och material.
    Sumitran-Holgersson, S
    University of Gothenburg, Sweden.
    Significantly accelerated wound healing of full-thickness skin using a novel composite gel of porcine acellular dermal matrix and human peripheral blood cells2017Ingår i: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 26, nr 2, s. 293-307Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Herein, we report the fabrication of a novel composite gel from decellularized gal-gal-knockout porcine skin and human peripheral blood mononuclear cells (hPBMC) for full-thickness skin wound healing. Decellularized skin extracellular matrix (ECM) powder was prepared via chemical treatment, freeze-drying and homogenization. The powder was mixed with culture medium containing hyaluronic acid to generate a pig skin gel (PSG). The effect of the gel in regeneration of full-thickness wound was studied in nude mice. We found significantly accelerated wound closure already on day 15 in animals treated with PSG only or PSG+hPBMC as compared to untreated and hyaluronic acid treated controls (p<0.05). Addition of the hPBMC to the gel resulted in marked increase of host blood vessels as well as the presence of human blood vessels. At day 25, histologically, the wounds in animals treated with PSG only or PSG+hPBMC were completely closed as compared to controls. Thus, the gel facilitated generation of new skin with well arranged epidermal cells and restored bilayer structure of the epidermis and dermis. These results suggest that porcine skin ECM gel together with human cells may be a novel and promising biomaterial for medical applications especially for patients with acute and chronic skin wounds.

  • 7.
    Mahlapuu, Margit
    et al.
    Promore Pharma AB, Sweden; University of Gothenburg, Sweden.
    Håkansson, Joakim
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Ringstad, Lovisa
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science.
    Björn, Camilla
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. University of Gothenburg, Sweden.
    Antimicrobial peptides: An emerging category of therapeutic agents2016Ingår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 6, nr DEC, artikel-id 194Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

    Ladda ner fulltext (pdf)
    fulltext
  • 8.
    Martínez, Claudia
    et al.
    Uppsala University, Sweden; University of Barcelona, Spain.
    Amery, Leanne
    AstraZeneca, UK.
    De Paoli, Giorgia
    University of Dundee, uk.
    Elofsson, Ulla
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel.
    Millqvist-Fureby, Anna
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel.
    Kwok, Stanley
    AstraZeneca, USA.
    López-Cabezas, Carmen
    Hospital Clínic Barcelona, Spain.
    Rosenberger, Marika
    Sanofi-Aventis Deutschland GmbH, Germany.
    Schoenau, Christian
    Sanofi-Aventis Deutschland GmbH, Germany.
    Wahlgren, Marie
    Lund University,Sweden.
    Paulsson, Mattias
    Uppsala University, Sweden.
    Examination of the Protein Drug Supply Chain in a Swedish University Hospital: Focus on Handling Risks and Mitigation Measures2023Ingår i: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Protein drugs, such as monoclonal antibodies, have proved successful in treating cancer and immune system diseases. The structural complexity of these molecules requires careful handling to ensure integrity and stability of the drug. In this study, a failure mode and effects analysis was performed based on a Gemba Walk method in a Swedish University Hospital. The Gemba Walk is focused on pharmacists observing the actual supply process steps from distributor, pharmacy cleanroom to patient administration. Relevant protein drugs are chosen based on sales statistics within the hospital and the corresponding wards were observed. Further is the Double Diamond design method used to identify major risks and deliver mitigation strategies. The study identified potential stress factors such as temperature, shock by impact, shaking, vibration and light exposure. There were also risks associated with porters’ and healthcare professionals’ lack of awareness and access to information. These risk factors may cause loss of efficacy and quality of the protein drug, potentially leading to patient safety concerns. In this study, a simulation is also performed to list measures that theoretically should be in place to ensure the quality of the protein drug, for example validated and protocol-based compounding in cleanroom, training and validated transports. © 2023 The Authors

  • 9.
    Matougui, Nada
    et al.
    Inserm, France.
    Boge, Lukas
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science.
    Groo, Anne-Claire
    Inserm, France.
    Umerska, Anita
    Inserm, France.
    Ringstad, Lovisa
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science.
    Bysell, Helena
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science.
    Saulnier, Patrick
    Inserm, France; CHU Angers, France.
    Lipid-based nanoformulations for peptide delivery2016Ingår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 502, nr 1-2, s. 80-97Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Nanoformulations have attracted a lot of attention because of their size-dependent properties. Among the array of nanoformulations, lipid nanoformulations (LNFs) have evoked increasing interest because of the advantages of their high degree of biocompatibility and versatility. The performance of lipid nanoformulations is greatly influenced by their composition and structure. Therapeutic peptides represent a growing share of the pharmaceutical market. However, the main challenge for their development into commercial products is their inherent physicochemical and biological instability. Important peptides such as insulin, calcitonin and cyclosporin A have been incorporated into LNFs. The association or encapsulation of peptides within lipid-based carriers has shown to protect the labile molecules against enzymatic degradation. This review describes strategies used for the formulation of peptides and some methods used for the assessment of association efficiency. The advantages and drawbacks of such carriers are also described.

  • 10.
    Nyström, Lina
    et al.
    Uppsala University, Sweden.
    Nordström, Randi
    Uppsala University, Sweden.
    Bramhill, Jane
    University of Manchester, UK.
    Saunders, Brian R.
    University of Manchester, UK.
    Álvarez-Asencio, Rubén
    KTH Royal Institute of Technology, Sweden; IMDEA Nanoscience, Spain.
    Rutland, Mark W.
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science. KTH Royal Institute of Technology, Sweden.
    Malmsten, Martin
    Uppsala University, Sweden.
    Factors affecting peptide interactions with surface-bound microgels2016Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, nr 2, s. 669-678Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Effects of electrostatics and peptide size on peptide interactions with surface-bound microgels were investigated with ellipsometry, confocal microscopy, and atomic force microscopy (AFM). Results show that binding of cationic poly-l-lysine (pLys) to anionic, covalently immobilized, poly(ethyl acrylate-co-methacrylic acid) microgels increased with increasing peptide net charge and microgel charge density. Furthermore, peptide release was facilitated by decreasing either microgel or peptide charge density. Analogously, increasing ionic strength facilitated peptide release for short peptides. As a result of peptide binding, the surface-bound microgels displayed pronounced deswelling and increased mechanical rigidity, the latter quantified by quantitative nanomechanical mapping. While short pLys was found to penetrate the entire microgel network and to result in almost complete charge neutralization, larger peptides were partially excluded from the microgel network, forming an outer peptide layer on the microgels. As a result of this difference, microgel flattening was more influenced by the lower Mw peptide than the higher. Peptide-induced deswelling was found to be lower for higher Mw pLys, the latter effect not observed for the corresponding microgels in the dispersed state. While the effects of electrostatics on peptide loading and release were similar to those observed for dispersed microgels, there were thus considerable effects of the underlying surface on peptide-induced microgel deswelling, which need to be considered in the design of surface-bound microgels as carriers of peptide loads, for example, in drug delivery or in functionalized biomaterials.

  • 11.
    Sohlenius-Sternbeck, Anna-Karin
    et al.
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemisk och farmaceutisk toxikologi. Medivir AB, Sweden.
    Terelius, Ylva
    Medivir AB, Sweden; ADMEYT AB, Sweden.
    Evaluation of ADMET Predictor in Early Discovery Drug Metabolism and Pharmacokinetics Project Work2022Ingår i: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 50, nr 2, s. 95-104Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A dataset consisting of measured values for LogD, solubility, metabolic stability in human liver microsomes (HLMs), and Caco-2 permeability was used to evaluate the prediction models for lipophilicity (S+LogD), water solubility (S+Sw_pH), metabolic stability in HLM (CYP_HLM_Clint), intestinal permeability (S+Peff), and P-glycoprotein (P-gp) substrate identification (P-gp substrate) in the software ADMET Predictor (AP) from Simulations Plus. The dataset consisted of a total of 4, 794 compounds, with at least data from metabolic stability determinations in HLM, from multiple discovery projects at Medivir. Our evaluation shows that the global AP models can be used for categorization of high and low values based on predicted results for metabolic stability in HLM and intestinal permeability, and to give good predictions of LogD (R25 0.79), guiding the synthesis of new compounds and for prioritizing in vitro ADME experiments. The model seems to overpredict solubility for the Medivir compounds, however. We also used the in-house datasets to build local models for LogD, solubility, metabolic stability, and permeability by using artificial neural network (ANN) models in the optional Modeler module of AP. Predictions of the test sets were performed with both the global and the local models, and the R2 values for linear regression for predicted versus measured HLM in vitro intrinsic clearance (CLint) based on logarithmic data were 0.72 for the in-house model and 0.53 for the AP model. The improved predictions with the local models are likely explained both by the specific chemical space of the Medivir dataset and laboratory-specific assay conditions for parameters that require biologic assay systems. .

  • 12.
    Stensen, Wenche
    et al.
    UiT The Arctic University of Norway, Norway; Lytix Biopharma AS, Norway.
    Turner, Rob
    MedPharm Ltd, UK.
    Brown, Marc
    MedPharm Ltd, UK; University of Hertfordshire, UK.
    Kondori, Nahid
    University of Gothenburg, Sweden.
    Svendsen, John Sigurd
    UiT The Arctic University of Norway, Norway; Lytix Biopharma AS, Norway.
    Svenson, Johan
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Short cationic antimicrobial peptides display superior antifungal activities toward Candidiasis and Onychomycosis in comparison with Terbinafine and Amorolfine2016Ingår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 13, nr 10, s. 3595-3600Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Novel antifungals are in high demand due to the challenges associated with resistant, persistent, and systemic fungal infections. Synthetic mimics of antimicrobial peptides are emerging as a promising class of compounds for antifungal treatment. In the current study, five synthetic cationic antimicrobial tripeptides were evaluated as antifungal therapeutics against 24 pathogenic strains of fungi. Three of the peptides displayed strong general antifungal properties at low micromolar inhibitory concentrations. The most promising peptide, compound 5, was selected and evaluated as an antifungal remedy for Candida albicans candidiasis in a human skin model and for the treatment of Trichophyton rubrum induced onychomycosis in an infected human nail model. Compound 5 was shown to display antifungal properties and a rapid mode of action superior to those of both the commercial comparators Loceryl and Lamisil. Compound 5 was also active against a clinical isolate of Candida albicans with acquired fluconazole resistance.

  • 13.
    Svagan, Anna J.
    et al.
    KTH Royal Institute of Technology, Sweden; University of Copenhagen, Denmark.
    Benjamins, Jan-Willem
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Life Science.
    Al-Ansari, Zeinab
    University of Copenhagen, Denmark.
    Shalom, Daniel Bar
    University of Copenhagen, Denmark.
    Müllertz, Anette
    University of Copenhagen, Denmark.
    Wågberg, Lars
    KTH Royal Institute of Technology, Sweden.
    Löbmann, Korbinian
    University of Copenhagen, Denmark.
    Solid cellulose nanofiber based foams – Towards facile design of sustained drug delivery systems2016Ingår i: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 244, s. 74-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Control of drug action through formulation is a vital and very challenging topic within pharmaceutical sciences. Cellulose nanofibers (CNF) are an excipient candidate in pharmaceutical formulations that could be used to easily optimize drug delivery rates. CNF has interesting physico-chemical properties that, when combined with surfactants, can be used to create very stable air bubbles and dry foams. Utilizing this inherent property, it is possible to modify the release kinetics of the model drug riboflavin in a facile way. Wet foams were prepared using cationic CNF and a pharmaceutically acceptable surfactant (lauric acid sodium salt). The drug was suspended in the wet-stable foams followed by a drying step to obtain dry foams. Flexible cellular solid materials of different thicknesses, shapes and drug loadings (up to 50 wt%) could successfully be prepared. The drug was released from the solid foams in a diffusion-controlled, sustained manner due to the presence of intact air bubbles which imparted a tortuous diffusion path. The diffusion coefficient was assessed using Franz cells and shown to be more than one order of magnitude smaller for the cellular solids compared to the bubble-free films in the wet state. By changing the dimensions of dry foams while keeping drug load and total weight constant, the drug release kinetics could be modified, e.g. a rectangular box-shaped foam of 8 mm thickness released only 59% of the drug after 24 h whereas a thinner foam sample (0.6 mm) released 78% of its drug content within 8 h. In comparison, the drug release from films (0.009 mm, with the same total mass and an outer surface area comparable to the thinner foam) was much faster, amounting to 72% of the drug within 1 h. The entrapped air bubbles in the foam also induced positive buoyancy, which is interesting from the perspective of gastroretentive drug-delivery.

  • 14.
    Svenson, Johan
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    På jakt efter nya läkemedel i Ishavet2016Ingår i: Naturvetare, ISSN 2000-2424, Vol. 6, s. 24-28Artikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
    Abstract [sv]

    Ungefär en tredjedel av alla läkemedel har sin källa i naturen. Forskaren Johan Svenson skriver själv om sin expedition i Arktis, där forskarna samlar in alger och andra organismer i sökandet efter nya molekyler, som till exempel kan bli ny antibiotika.

  • 15.
    Urimi, Dileep
    et al.
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel. University of Iceland, Iceland.
    Widenbring, Ronja
    RISE Research Institutes of Sweden.
    Perez, Oswaldo
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel. University of Iceland, Iceland.
    Gedda, Lars
    Uppsala University, Uppsala.
    Edwards, Katarina
    Uppsala University, Uppsala.
    Loftsson, Thorsteinn
    University of Iceland, Iceland.
    Schipper, Nicolaas
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel.
    Formulation development and upscaling of lipid nanocapsules as a drug delivery system for a novel cyclic GMP analogue intended for retinal drug delivery2021Ingår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 602, artikel-id 120640Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lipid nanocapsules (LNCs) were prepared with a novel cyclic GMP analogue, DF003, intended for the treatment of neurodegenerative retinal degenerations. LNCs loaded with DF003 were prepared by a phase inversion method and characterized for particle size, polydispersity index, drug loading, entrapment efficiency, stability, and in vitro drug release. Particle size, PdI and zeta potential of selected optimized formulation were 76 ± 1.2 nm, 0.16 ± 0.02, and −11.6 ± 0.4 mV, respectively, with an entrapment efficiency of 69 ± 0.5%. The selected formulation showed a sustained drug release for up to 6 days in phosphate buffer as well as in vitreous components. Stability evaluation of LNCs in presence of vitreous components demonstrated structural stability and compatibility. Further, the nanoparticle preparation process was upscaled to 1000 times (10 L) of the typical lab scale (0.01 L). Product parameters were observed to be unaffected by the upscaling, demonstrating that the LNCs were of the same quality as those prepared at lab scale. Additionally, the manufacturing process was adapted and assessed for a continuous production of LNCs to leverage it for industrial viability. Overall, these findings reveal the remarkable potential of LNCs as drug delivery vehicles and their possibility for clinical translation.

    Ladda ner fulltext (pdf)
    fulltext
  • 16.
    Zhao, Chenyan
    et al.
    Uppsala University, Sweden.
    Chirkova, Anna
    Juvabis AG, Switzerland.
    Rosenborg, Staffan
    Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Villar, Rodrigo Palma
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel.
    Lindberg, Johan
    RISE Research Institutes of Sweden, Bioekonomi och hälsa, Kemiska processer och läkemedel.
    Hobbie, Sven N
    University of Zurich, Switzerland.
    Friberg, Lena E
    Uppsala University, Sweden.
    Population pharmacokinetics of apramycin from first-in-human plasma and urine data to support prediction of efficacious dose2022Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 77, nr 10, s. 2718-2728Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Apramycin is under development for human use as EBL-1003, a crystalline free base of apramycin, in face of increasing incidence of multidrug-resistant bacteria. Both toxicity and cross-resistance, commonly seen for other aminoglycosides, appear relatively low owing to its distinct chemical structure. OBJECTIVES: To perform a population pharmacokinetic (PPK) analysis and predict an efficacious dose based on data from a first-in-human Phase I trial. METHODS: The drug was administered intravenously over 30 min in five ascending-dose groups ranging from 0.3 to 30 mg/kg. Plasma and urine samples were collected from 30 healthy volunteers. PPK model development was performed stepwise and the final model was used for PTA analysis. RESULTS: A mammillary four-compartment PPK model, with linear elimination and a renal fractional excretion of 90%, described the data. Apramycin clearance was proportional to the absolute estimated glomerular filtration rate (eGFR). All fixed effect parameters were allometrically scaled to total body weight (TBW). Clearance and steady-state volume of distribution were estimated to 5.5 L/h and 16 L, respectively, for a typical individual with absolute eGFR of 124 mL/min and TBW of 70 kg. PTA analyses demonstrated that the anticipated efficacious dose (30 mg/kg daily, 30 min intravenous infusion) reaches a probability of 96.4% for a free AUC/MIC target of 40, given an MIC of 8 mg/L, in a virtual Phase II patient population with an absolute eGFR extrapolated to 80 mL/min. CONCLUSIONS: The results support further Phase II clinical trials with apramycin at an anticipated efficacious dose of 30 mg/kg once daily.

1 - 16 av 16
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf