Browsing by Subject "PEG"

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  • Shakirova, Julia R.; Sadeghi, Amir; Koblova, Alla A.; Chelushkin, Pavel S.; Toropainen, Elisa; Tavakoli, Shirin; Kontturi, Leena-Stiina; Lajunen, Tatu; Tunik, Sergey P.; Urtti, Arto (2020)
    Two iridium [Ir(NC)(2)(NN)](+) complexes with the diimine NN ligand containing a long polymethylene hydrophobic chain were synthesized and characterized by using NMR and ESI mass-spectrometry: NN - 2-(1-hexadecyl-1H-imidazol-2-yl)pyridine, NC - methyl-2-phenylquinoline-4-carboxylate (Ir1) and 2-phenylquinoline-4-carboxylic acid (Ir2). These complexes were used to prepare the luminescent PEGylated DPPC liposomes (DPPC/DSPE-PEG2000/Ir-complex = 95/4.5/1 mol%) using a thin film hydration method. The narrowly dispersed liposomes had diameters of about 110 nm. The photophysics of the complexes and labeled liposomes were carefully studied. Ir1 and Ir2 give red emission (lambda(em) = 667 and 605 nm) with a lifetime in the microsecond domain and quantum yields of 4.8% and 10.0% in degassed solution. Incorporation of the complexes into the liposome lipid bilayer results in shielding of the emitters from interaction with molecular oxygen and partial suppression of excited state nonradiative relaxation due to the effect of the relatively rigid bilayer matrix. Delivery of labeled liposomes to the cultured ARPE-19 cells demonstrated the usefulness of Ir1 and Ir2 in cellular imaging. Labeled liposomes were then injected intravitreally into rat eyes and imaged successfully with optical coherence tomography and funduscopy. In conclusion, iridium complexes enabled the successful labeling and imaging of liposomes in cells and animals.
  • Berg, Staffan (Helsingfors universitet, 2013)
    The usage of polymer conjugation to modulate the biopharmaceutical behavior of both protein drugs as well as small molecule drugs is discussed. Emphasis has been given to polyethylene glycol (PEG) and poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) but also other polymers are looked into. Drug products on the market as well as drug candidates in clinical trials are used as examples when reviewing different polymers. The material is looked upon from a biopharmaceutical point of view. In the experimental part a polymer-drug conjugate for the treatment of ovarian cancer is synthesized and characterized. The conjugate has a HPMA polymer backbone with the anticancer drug gemcitabine attached through enzymatically labile Gly-Phe-Leu-Gly linkers. The conjugate is expected to target passively and actively to cancer tissue. The enhanced permeation and retention effect is responsible for the passive targeting, while Fab' fragments of OV-TL16 monoclonal antibodies provide the active targeting of the copolymer conjugate. In vitro cytotoxicity studies of a PHPMA-gemcitabine conjugate (without active targeting) was carried out on two ovarian cancer cell lines, A2780S and A2780AD. The IC50 values of the conjugate was shown to be 50.6 nM and 14.3 nM for A2780S and A2780AD, respectively. The corresponding IC50 values for free gemcitabine were 7.0 nM for the A2780S cell line and 3.9 nM for A2780AD cells. A preliminary in vivo efficacy study in mice with subcutaneous A2780AD tumor xenografts showed that a PHMA-gemcitabine conjugate given at a dose of 15 mg/kg (gemcitabine equivalence) was able to shrink the tumor volume by 50 % while only inducing minor body weight loss.
  • Ruohoalho, Johanna; Aro, Katri; Makitie, Antti A.; Atula, Timo; Haapaniemi, Aaro; Keski-Santti, Harri; Kylanpaa, Leena; Takala, Annika; Back, Leif J. (2017)
    Percutaneous endoscopic gastrostomy (PEG) is often the treatment of choice in head and neck cancer (HNC) patients needing long-term nutritional support. Prospective studies on PEG tube placement in an otorhinolaryngologist service are lacking. At our hospital, otolaryngologist-head and neck (ORL-HN) surgeons-have performed PEG insertions for HNC patients since 2008. We prospectively analyzed 127 consecutive HNC patients who received their PEG tubes at the Department of Otorhinolaryngology-head and neck surgery, and evaluated the outcome of PEG tube insertions performed by ORL-HN surgeons. To compare time delays before and after, PEG placement service was transferred from gastrointestinal surgeons to ORL-HN surgeons, and we retrospectively analyzed a separate group of 110 HNC patients who had earlier received PEG tubes at the Department of Gastrointestinal Surgery. ORL-HN surgeons' success rate in PEG insertion was 97.6%, leading to a final prospective study group of 124 patients. Major complications occurred in four (3.2%): two buried bumper syndromes, one subcutaneous hemorrhage leading to an abscess in the abdominal wall, and one metastasis at the PEG site. The most common minor complication was peristomal granulomatous tissue affecting 23 (18.5%) patients. After the change in practice, median time delay before PEG insertion decreased from 13 to 10 days (P <0.005). The proportion of early PEG placements within 0-3 days increased from 3.6 to 14.6% (P <0.005). PEG tube insertion seems to be a safe procedure in the hands of an ORL-HN surgeon. Independence from gastrointestinal surgeons' services reduced the time delay and improved the availability of urgent PEG insertions.
  • Haider, Malik Salman; Luebtow, Michael M.; Endres, Sebastian; Forster, Stefan; Flegler, Vanessa J.; Boettcher, Bettina; Aseyev, Vladimir; Pöppler, Ann-Christin; Luxenhofer, Robert (2020)
    Polymeric micelles are typically characterized as core-shell structures. The hydrophobic core is considered as a depot for hydrophobic molecules, and the corona-forming block acts as a stabilizing and solubilizing interface between the core and aqueous milieu. Tremendous efforts have been made to tune the hydrophobic block to increase the drug loading and stability of micelles, whereas the role of hydrophilic blocks is rarely investigated in this context, with poly(ethylene glycol) (PEG) being the gold standard of hydrophilic polymers. To better understand the role of the hydrophilic corona, a small library of structurally similar A-B-A-type amphiphiles based on poly(2-oxazoline)s and poly(2-oxazine)s is investigated by varying the hydrophilic block A utilizing poly(2-methyl-2-oxazoline) (pMeOx; A) or poly(2-ethyl-2-oxazoline) (pEtOx; A*). In terms of hydrophilicity, both polymers closely resemble PEG. The more hydrophobic block B bears either a poly(2-oxazoline) and poly(2-oxazine) backbone with C3 (propyl) and C4 (butyl) side chains. Surprisingly, major differences in loading capacities from A-B-A > A*-B-A > A*-B-A* is observed for the formulation with two poorly water-soluble compounds, curcumin and paclitaxel, highlighting the importance of the hydrophilic corona of polymer micelles used for drug formulation. The formulations are also characterized by various nuclear magnetic resonance spectroscopy methods, dynamic light scattering, cryogenic transmission electron microscopy, and (micro) differential scanning calorimetry. Our findings suggest that the interaction between the hydrophilic block and the guest molecule should be considered an important, but previously largely ignored, factor for the rational design of polymeric micelles.