| 1. |
- D. Holmkvist, Alexander, et al.
(författare)
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Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.
- 2016
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 499:1-2, s. 351-357
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Tidskriftsartikel (refereegranskat)abstract
- Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS.
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| 2. |
- Etemadi, Leila, et al.
(författare)
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Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Neural interfaces which allow long-term recordings in deep brain structures in awake freely moving animals have the potential of becoming highly valuable tools in neuroscience. However, the recording quality usually deteriorates over time, probably at least partly due to tissue reactions caused by injuries during implantation, and subsequently micro-forces due to a lack of mechanical compliance between the tissue and neural interface. To address this challenge, we developed a gelatin embedded neural interface comprising highly flexible electrodes and evaluated its long term recording properties. Bundles of ultrathin parylene C coated platinum electrodes (N = 29) were embedded in a hard gelatin based matrix shaped like a needle, and coated with Kollicoat™ to retard dissolution of gelatin during the implantation. The implantation parameters were established in an in vitro model of the brain (0.5% agarose). Following a craniotomy in the anesthetized rat, the gelatin embedded electrodes were stereotactically inserted to a pre-target position, and after gelatin dissolution the electrodes were further advanced and spread out in the area of the subthalamic nucleus (STN). The performance of the implanted electrodes was evaluated under anesthesia, during 8 weeks. Apart from an increase in the median-noise level during the first 4 weeks, the electrode impedance and signal-to-noise ratio of single-units remained stable throughout the experiment. Histological postmortem analysis confirmed implantation in the area of STN in most animals. In conclusion, by combining novel biocompatible implantation techniques and ultra-flexible electrodes, long-term neuronal recordings from deep brain structures with no significant deterioration of electrode function were achieved.
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| 3. |
- Fridén-Saxin, Maria, 1979, et al.
(författare)
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Chroman-4-one and chromone based somatostatin beta-turn mimetics
- 2016
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234. ; 114, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- A scaffold approach has been used to develop somatostatin beta-turn mimetics based on chroman-4-one and chromone ring systems. Such derivatives could adopt conformations resembling type II or type II' beta-turns. Side chain equivalents of the crucial Trp8 and Lys9 in somatostatin were introduced in the 2- and 8-positions of the scaffolds using efficient reactions. Interestingly, this proof-of-concept study shows that 4 and 9 have K-i-values in the low mu M range when evaluated for their affinity for the sst2 and sst4 receptors. (C) 2016 Elsevier Masson SAS. All rights reserved.
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| 4. |
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| 5. |
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| 6. |
- Dyrager, Christine, 1975, et al.
(författare)
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Inhibitors and promoters of tubulin polymerization : Synthesis and biological evaluation of chalcones and related dienones as potential anticancer agents
- 2011
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 19:8, s. 2659-2665
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Tidskriftsartikel (refereegranskat)abstract
- A series of dihalogenated chalcones and structurally related dienones were synthesized and evaluated for their antiproliferative activity in 10 different cancer cell lines and for their effect on microtubule assembly. All compounds showed cytotoxic activity, with IC50 values in the 5-280 mu M range depending on the chalcone structure and the cell line. Five of the compounds were found to be tubulin polymerization inhibitors. In contrast, one of the compounds was found to stabilize tubulin to the same extent as the anticancer drug docetaxel. Molecular modeling suggested that the tubulin inhibitors bind to the colchicine binding site of beta-tubulin while the novel tubulin stabilization agent seems to interact with the paclitaxel binding site.
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| 7. |
- Dyrager, Christine, 1975, et al.
(författare)
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2,6,8-Trisubstituted 3-hydroxychromone derivatives as fluorophores for live-cell imaging.
- 2009
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Ingår i: Chemistry (Weinheim an der Bergstrasse, Germany). - : Wiley. - 1521-3765 .- 0947-6539. ; 15:37, s. 9417-23
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Tidskriftsartikel (refereegranskat)abstract
- We present the synthesis and photophysical characterisation of a series of structurally diverse, fluorescent 2,6,8-trisubstituted 3-hydroxychromone derivatives with high fluorescence quantum yields and molar extinction coefficients. Two of these derivatives (9 and 10 a) have been studied as fluorophores for cellular imaging in HeLa cells and show excellent permeability and promising fluorescence properties in a cellular environment. In addition, we have demonstrated by photophysical characterisation of 3-isobutyroxychromone derivatives that esterification of the 3-hydroxyl group results in acceptable and useful fluorescence properties.
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| 8. |
- Fridén-Saxin, Maria, 1979, et al.
(författare)
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Synthesis of 2-alkyl-substituted chromone derivatives using microwave irradiation.
- 2009
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Ingår i: The Journal of organic chemistry. - : American Chemical Society (ACS). - 1520-6904 .- 0022-3263. ; 74:7, s. 2755-9
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Tidskriftsartikel (refereegranskat)abstract
- A base-promoted condensation between 2-hydroxyacetophenones and aliphatic aldehydes has been studied. The reaction has been optimized to afford 2-alkyl-substituted 4-chromanones in an efficient manner using microwave heating. Performing the reaction using diisopropylamine in EtOH at 170 degrees C for 1 h gave moderate to high yields (43-88%). The 4-chromanones could be further converted into highly functionalized 2,3,6,8-tetrasubstituted chromones in which a 3-substituent (acetate, amine, or bromine) was introduced via straightforward chemical transformations.
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| 9. |
- Friberg, Annika, et al.
(författare)
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Bicyclo[2.2.2]octane-derived chiral ligands-synthesis and application of BODOLs in the asymmetric reduction of acetophenone with catecholborane
- 2008
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Ingår i: Tetrahedron: Asymmetry. - : Elsevier BV. - 0957-4166. ; 19:15, s. 1765-1777
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Tidskriftsartikel (refereegranskat)abstract
- An improved synthetic route to the bicyclo[2.2.2]octane-2,6-diol ligands (2,6-BODOLS) allowed an increased structural variation of the ligand side-arm. The addition of aromatic or vinylic Grignard reagents to hydroxyketone 1 was highly selective and ligands 3f-3I were isolated in 84-97% yield. The addition of alkyl Grignard reagents containing beta-hydrogens resulted in lower yields (13-71%) due to competing ketone reduction. A number of 2,5-BODOLs were synthesized using a similar methodology. The ligands, together with Ti(OiPr)(4), were tested in the asymmetric reduction of acetophenone with catecholborane (up to 98% ee). 1-Naphthyl-BODOL 3i was employed as an allylboration reagent to benzaldehyde together with Sc(OTf)(3), resulting in (1S)-1-phenyl-3-buten-1-ol in 80% ee. (C) 2008 Elsevier Ltd. All rights reserved.
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| 10. |
- Olsson, Cecilia, et al.
(författare)
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Bicyclic diols and related derivatives as catalysts for the asymmetric diethylzinc addition to benzaldehyde
- 2008
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Ingår i: Tetrahedron: Asymmetry. - : Elsevier BV. - 0957-4166. ; 19:12, s. 1476-1483
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Tidskriftsartikel (refereegranskat)abstract
- Chiral bicyclic diols based on bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane have been synthesized and their catalytic capacity in the asymmetric diethylzinc addition to benzaldehyde compared with those described for previously synthesized 2,6-bicyclo[2.2.2]octane-diols (BODOLs). The influence of the number of coordinating sites and the distance between them were studied. (C) 2008 Elsevier Ltd. All rights reserved.
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