Browsing by Subject "COPOLYMER"

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  • Pakkasjarvi, Niklas; Taskinen, Seppo (2018)
    Introduction Sphincter insufficiency is mostly associated with neurogenic and some structural abnormalities in the pediatric population. As a mini-invasive treatment, urethral bulking agents have been used to treat this problem. Objective The aim was to evaluate if technical success, defined as intraoperative increase in abdominal leak point pressure (ALPP), predicts the outcome of the treatment of sphincter insufficiency with urethral bulking agent. Study design We reviewed all children treated first time with dextranomer/hyaluronicacid (Dx/HA) copolymer (Deflux) for urethral sphincter insufficiency and who intraoperatively had ALPPs measured during 2004-2014. Patient characteristics, change in urinary continence and the duration of the possible response were evaluated in neurogenic and non-neurogenic cases. Results The median age of the patients was 7.8 years (range 4.1-14.5) at initial treatment and median volume of Dx/HA instilled was 3.5 mL (IQR 2-5). Twelve patients had neurogenic disease and 15 had nonneurogenic disease. Median ALPPs before and after the injections were 19 cmH(2)O (IQR 14-28) and 70 cmH(2)O (IQR 48-80), p <0.001. Increases in ALPPs were similar in both patient groups (p = 0.661) and in 17 patients with any response and 10 patients with no response (p = 0.267). In patients with any response the median duration of the response was only 0.8 years (IQR 0.09-2.0). During a median follow-up of 4.9 years (range 1.7-11.8), 15 patients received one to three repeat injections and eight patients went through sling or bladder neck operation (Summary table). During repeat injections, the preoperative ALPPs had returned injections, the preoperative ALPPs had returned to the original levels. Currently, 20% are continent or almost continent with one or more Dx/HA injections. In half of the patients with neurogenic bladder, compliance or volume deteriorated slightly in follow-up. Five out of 15 patients who reached puberty become continent spontaneously after failed bladder neck injection. Discussion Intraoperative ALPPs increased significantly in most patients during the procedure. However, only 52% of the patients experienced more than 1 month of success after the procedure, and even in those the effect lasted mostly under a year. With one to four injections one-fifth seem to have had a good longterm result. Although the long-term success rate is limited, bulking agent injection allowed the patients with spontaneous voiding to continue it and the injection did not prevent future treatments. Conclusion Intraoperative increased ALPP does not predict a good long-term outcome after Dx/HA injection. At the end, only a fifth of our patients had good result with one or more Dx/HA injections. A change in bladder behavior is possible after treatment.
  • Moquin, Alexandre; Ji, Jeff; Neibert, Kevin; Winnik, Francoise M.; Maysinger, Dusica (2018)
    Polymersomes are attractive nanocarriers for hydrophilic and lipophilic drugs; they are more stable than liposomes, tunable, and relatively easy to prepare. The copolymer composition and molar mass are critical features that determine the physicochemical properties of the polymersomes including the rate of drug release. We used the triblockcopolymer, poly(2-methyl-2-oxazoline)-block-poly-(dimethysiloxane)-block-poly(2-methyl-2-oxazoline) (PIVIOXA-PDIVIS-PMOXA), to form amphipathic polymersomes capable of loading proteins and small hydrophobic agents. The selected agents were unstable neurotrophins (nerve growth factor and brain -derived neurotrophic factor), a large protein CD109, and the fluorescent drug curcumin. We prepared, characterized, and tested polymersomes loaded with selected agents in 2D and 3D biological models. Curcumin-loaded and rhodamine-bound PMOXA-PDMS-PMOXA polymersomes were used to visualize them inside cells. NMethyl-D-aspartate receptor (NNIDAR) agonists and antagonists were also covalently attached to the surface of polymersomes for targeting neurons. Labeled and unlabeled polymersomes with or without loaded agents were characterized using dynamic light scattering (DLS), UV-vis fluorescence spectroscopy, and asymmetrical flow field-flow fractionation (AF(4)). Polymersomes were imaged and tested for biological activity in human and murine fibroblasts, murine macrophages, primary murine dorsal root ganglia, and murine hippocampal cultures. Polymersomes were rapidly internalized and there was a clear intracellular co-localization of the fluorescent drug (curcumin) with the fluorescent rhodamine-labeled polymersomes. Polymersomes containing CD109, a glycosylphosphatidylinositol-anchored protein, promoted cell migration in the model of wound healing. Nerve growth factor-loaded polymersomes effectively enhanced neurite outgrowth in dissociated and explanted dorsal root ganglia. Brain -derived neurotrophic factor increased dendritic spine density in serum-deprived hippocampal slice cultures. NMDAR agonist-and antagomst-functionalized polymersomes targeted selectively neurons over filial cells in mixed cultures. Collectively, the study reveals the successful incorporation into polymersomes of biologically active trophic factors and small hydrophilic agents that retain their biological activity in vitro, as demonstrated in selected central and peripheral tissue models.
  • Tiainen, Tony; Lobanova, Marina; Karjalainen, Erno; Tenhu, Heikki; Hietala, Sami (2020)
    Nanodiamonds (NDs) can considerably improve the mechanical and thermal properties of polymeric composites. However, the tendency of NDs to aggregate limits the potential of these non-toxic, mechanically- and chemically-robust nanofillers. In this work, tough, flexible, and stimuli-responsive polyelectrolyte films composed of cross-linked poly(butyl acrylate-co-dimethylaminoethyl methacrylate) (P(BA-co-DMAEMA)) were prepared by photopolymerization. The effects of the added carboxylate-functionalized NDs on their mechanical and stimuli-responsive properties were studied. When the negatively charged NDs were added to the polymerization media directly, the mechanical properties of the films changed only slightly, because of the uneven distribution of the aggregated NDs in the films. In order to disperse and distribute the NDs more evenly, a prepolymerized polycation block copolymer complexing agent was used during the photopolymerization process. This approach improved the mechanical properties of the films and enhanced their thermally-induced, reversible phase-transition behavior.
  • Fowler, Michael Andrew; Duhamel, Jean; Qiu, Xing Ping; Korchagina, Evgeniya; Winnik, Francoise M. (2018)
    The temperature-dependent behavior of aqueous solutions composed of a small amount of monodisperse poly(N-isopropylacrylamide) (PNIPAM) labeled at one or both ends with pyrene (Py-n-PNIPAM with n = 1 or 2) and a 10-fold excess of a nonfluorescent poly(N-isopropylacrylamide) (PNIPAM(22K), M-n = 22 000 g/mol) was characterized using steady-state (SSF) and time-resolved (TRF) fluorescence. Turbidimetry studies indicated that all solutions exhibited two temperature-induced transitions: one at T-upsilon the cloud point of the pyrene-labeled polymers, and one at T-c22, the cloud point of PNIPAM(22K). These two transitions were also inferred from a decrease in the excimer-to-monomer fluorescence intensity ratio, namely, the I-E/I-M ratio, obtained from SSF spectra. TRF decays of the pyrene monomer were acquired and fitted with a sum of exponentials to obtain the number-average lifetime (tau). Plots of (1) versus temperature also showed transitions at T-c and T-c22. The changes in behavior observed at T, for both I-E/I-M and (tau) were consistent with those observed for solutions of solely Py-n-PNIPAM samples. The transitions found at T-c22 for the Pyn-PNIPAM solutions with PNIPAM(22K) were not observed in aqueous solutions of Py-n-PNIPAM without PNIPAM(22K). They were explained by invoking substantial mixing of labeled and unlabeled chains as temperature exceeded Tc-22. This mixing could only occur if the mesoglobules composed of labeled chains were not "frozen" at temperatures above T-c22 despite forming stable entities in this temperature range. This phenomenon was rationalized by considering the difference in the characteristic reptation time of the chains found in a Py-n-PNIPAM and PNIPAM(22K) mesoglobule at temperatures larger than T-c22.
  • 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.