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Nicolas Tsapis - One of the best experts on this subject based on the ideXlab platform.
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Comb-Like Fluorophilic-Lipophilic-Hydrophilic Polymers for Nanocapsules as Ultrasound Contrast Agents
Biomacromolecules, 2018Co-Authors: Sophie Houvenagel, Laurence Moine, Guilherme Picheth, Annie Brûlet, Alexis Chennevière, Vincent Faugeras, Camille Dejean, Olivier Couture, Nicolas Huang, Nicolas TsapisAbstract:Imaging the enhanced permeation and retention effect by ultrasound is hindered by the large size of commercial ultrasound contrast agents (UCAs). To obtain nanosized UCAs, triblock copolymers of poly(ethylene glycol)-polylactide-poly(1H,1H,2H,2H-heptadecafluorodecyl methacrylate) (PEG-PLA-PFMA) with distinct numbers of perfluorinated pendant chains (5, 10, or 20) are synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. Nanocapsules (NCs) containing Perfluorooctyl Bromide (PFOB) intended as UCAs are obtained with a 2-fold increase in PFOB encapsulation efficiency in fluorinated NCs as compared with plain PEG-PLA NCs thanks to fluorous interactions. NC morphology is strongly influenced by the number of perfluorinated chains and the amount of polymer used for formulation, leading to peculiar capsules with several PFOB cores at high PEG-PLA-PFMA 20 amount and single-cored NCs with a thinner shell at low fluorinated polymer amount, as confirmed by small-angle neutron scattering. Finally, fluorinated NCs yield higher in vitro ultrasound signal compared with PEG-PLA NCs, and no in vitro cytotoxicity is induced by fluorinated polymers and their degradation products. Our results highlight the benefit of adding comb-like fluorinated blocks in PEG-PLA polymers to modify the nanostructure and enhance the echogenicity of nanocapsules intended as UCAs.
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Comb-Like Fluorophilic-Lipophilic-Hydrophilic Polymers for Nanocapsules as Ultrasound Contrast Agents
Biomacromolecules, 2018Co-Authors: Sophie Houvenagel, Laurence Moine, Guilherme Picheth, Annie Brûlet, Alexis Chennevière, Vincent Faugeras, Camille Dejean, Olivier Couture, Nicolas Huang, Nicolas TsapisAbstract:© 2018 American Chemical Society. Imaging the enhanced permeation and retention effect by ultrasound is hindered by the large size of commercial ultrasound contrast agents (UCAs). To obtain nanosized UCAs, triblock copolymers of poly(ethylene glycol)-polylactide-poly(1H,1H,2H,2H-heptadecafluorodecyl methacrylate) (PEG-PLA-PFMA) with distinct numbers of perfluorinated pendant chains (5, 10, or 20) are synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. Nanocapsules (NCs) containing Perfluorooctyl Bromide (PFOB) intended as UCAs are obtained with a 2-fold increase in PFOB encapsulation efficiency in fluorinated NCs as compared with plain PEG-PLA NCs thanks to fluorous interactions. NC morphology is strongly influenced by the number of perfluorinated chains and the amount of polymer used for formulation, leading to peculiar capsules with several PFOB cores at high PEG-PLA-PFMA20amount and single-cored NCs with a thinner shell at low fluorinated polymer amount, as confirmed by small-angle neutron scattering. Finally, fluorinated NCs yield higher in vitro ultrasound signal compared with PEG-PLA NCs, and no in vitro cytotoxicity is induced by fluorinated polymers and their degradation products. Our results highlight the benefit of adding comb-like fluorinated blocks in PEG-PLA polymers to modify the nanostructure and enhance the echogenicity of nanocapsules intended as UCAs.
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Comb-Like Fluorophilic-Lipophilic-Hydrophilic Polymers for Nanocapsules as Ultrasound Contrast Agents
2018Co-Authors: Sophie Houvenagel, Laurence Moine, Guilherme Picheth, Vincent Faugeras, Camille Dejean, Olivier Couture, Nicolas Huang, Annie Brûlet, Alexis Chennevière, Nicolas TsapisAbstract:Imaging the enhanced permeation and retention effect by ultrasound is hindered by the large size of commercial ultrasound contrast agents (UCAs). To obtain nanosized UCAs, triblock copolymers of poly(ethylene glycol)-polylactide-poly(1H,1H,2H,2H-heptadecafluorodecyl methacrylate) (PEG-PLA-PFMA) with distinct numbers of perfluorinated pendant chains (5, 10, or 20) are synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. Nanocapsules (NCs) containing Perfluorooctyl Bromide (PFOB) intended as UCAs are obtained with a 2-fold increase in PFOB encapsulation efficiency in fluorinated NCs as compared with plain PEG-PLA NCs thanks to fluorous interactions. NC morphology is strongly influenced by the number of perfluorinated chains and the amount of polymer used for formulation, leading to peculiar capsules with several PFOB cores at high PEG-PLA-PFMA20 amount and single-cored NCs with a thinner shell at low fluorinated polymer amount, as confirmed by small-angle neutron scattering. Finally, fluorinated NCs yield higher in vitro ultrasound signal compared with PEG-PLA NCs, and no in vitro cytotoxicity is induced by fluorinated polymers and their degradation products. Our results highlight the benefit of adding comb-like fluorinated blocks in PEG-PLA polymers to modify the nanostructure and enhance the echogenicity of nanocapsules intended as UCAs
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the performance of pegylated nanocapsules of Perfluorooctyl Bromide as an ultrasound contrast agent
Biomaterials, 2010Co-Authors: Raquel Diazlopez, Nicolas Tsapis, S Lori Bridal, Danielle Jaillard, Mathieu Santin, Valérie Nicolas, Pierre Chaminade, Danielle Libong, Veronique Marsaud, Christine VauthierAbstract:The surface of polymeric nanocapsules used as ultrasound contrast agents (UCAs) was modified with PEGylated phospholipids in order to escape recognition and clearance by the mononuclear phagocyte system and achieve passive tumor targeting. Nanocapsules consisted of a shell of poly(lactide-co-glycolide) (PLGA) encapsulating a liquid core of Perfluorooctyl Bromide (PFOB). They were decorated with poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) incorporated in the organic phase before the solvent emulsification–evaporation process. The influence of DSPE-PEG concentration on nanocapsule size, surface charge, morphology, hydrophobicity and complement activation was evaluated. Zeta potential measurements, Hydrophobic interaction chromatography and complement activation provide evidence of DSPE-PEG presence at nanocapsule surface. Electronic microscopy reveals that the core/shell structure is preserved up to 2.64 mg of DSPE-PEG for 100 mg PLGA. In vivo ultrasound imaging was performed in mice bearing xenograft tumor with MIA PaCa-2 cells, either after an intra-tumoral or intravenous injection of nanocapsules. Tumor was observed only after the intra-tumoral injection. Despite the absence of echogenic signal in the tumor after intravenous injection of nanocapsules, histological analysis reveals their accumulation within the tumor tissue demonstrating that tissue distribution is not the unique property required for ultrasound contrast agents to be efficient.
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surfactant dependent morphology of polymeric capsules of Perfluorooctyl Bromide influence of polymer adsorption at the dichloromethane water interface
Journal of Colloid and Interface Science, 2008Co-Authors: Emilia Pisani, Elias Fattal, Juliane Paris, Catherine Ringard, Veronique Rosilio, Nicolas TsapisAbstract:In a strategy to develop more stable ultrasound contrast agents (UCAs), we have designed a process to obtain nano/microcapsules with a single core of liquid perfluorocarbon within a biodegradable polymeric shell of homogeneous thickness. During the optimization of Perfluorooctyl Bromide (PFOB) encapsulation by solvent emulsion-evaporation, a marked influence of surfactants has been observed. While sodium cholate leads to spherical capsules of homogeneous thickness, sodium taurocholate induces to the formation of "acorn"-particles with one hemisphere of PFOB and another one of PLGA, and polyvinyl alcohol is responsible for the coexistence of both morphologies. Whereas the theoretical model proposed by Torza and Mason [J. Colloid Interface Sci. 33 (1970) 67] fails to predict the observed morphologies, microscopic observations of the evaporation and interfacial tension measurements provide an insight into the mechanism of formation of these structures. Most probably, there is a competition between PLGA and the surfactant stabilizing the emulsion at the dichloromethane-water interface. If PLGA is able to adsorb at the interface, the core-shell morphology is obtained, otherwise the acorn morphology is preferentially formed. When the surfactant rearrangement at the interface is long (>30 min), a coexistence of morphologies can be obtained.
Frederic Gerber - One of the best experts on this subject based on the ideXlab platform.
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fluidization of a dipalmitoyl phosphatidylcholine monolayer by fluorocarbon gases potential use in lung surfactant therapy
Biophysical Journal, 2006Co-Authors: Marie Pierre Krafft, Frederic Gerber, Thierry F Vandamme, Michel Goldmann, Philippe FontaineAbstract:Fluorocarbon gases (gFCs) were found to inhibit the liquid-expanded (LE)/liquid-condensed (LC) phase transition of dipalmitoyl phosphatidylcholine (DPPC) Langmuir monolayers. The formation of domains of an LC phase, which typically occurs in the LE/LC coexistence region upon compression of DPPC, is prevented when the atmosphere above the DPPC monolayer is saturated with a gFC. When contacted with gFC, the DPPC monolayer remains in the LE phase for surface pressures lower than 38 mN m−1, as assessed by compression isotherms and fluorescence microscopy (FM). Moreover, gFCs can induce the dissolution of preexisting LC phase domains and facilitate the respreading of the DPPC molecules on the water surface, as shown by FM and grazing incidence x-ray diffraction. gFCs have thus a highly effective fluidizing effect on the DPPC monolayer. This gFC-induced fluidizing effect was compared with the fluidizing effect brought about by a mixture of unsaturated lipids and proteins, namely the two commercially available lung surfactant substitutes, Curosurf and Survanta, which are derived from porcine and bovine lung extracts, respectively. The candidate FCs were chosen among those already investigated for biomedical applications, and in particular for intravascular oxygen transport, i.e., Perfluorooctyl Bromide, Perfluorooctylethane, bis(perfluorobutyl)ethene, perfluorodecalin, and perfluorooctane. The fluidizing effect is most effective with the linear FCs. This study suggests that FCs, whose biocompatibility is well documented, may be useful in lung surfactant substitute compositions.
Marie Pierre Krafft - One of the best experts on this subject based on the ideXlab platform.
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fluidization of a dipalmitoyl phosphatidylcholine monolayer by fluorocarbon gases potential use in lung surfactant therapy
Biophysical Journal, 2006Co-Authors: Marie Pierre Krafft, Frederic Gerber, Thierry F Vandamme, Michel Goldmann, Philippe FontaineAbstract:Fluorocarbon gases (gFCs) were found to inhibit the liquid-expanded (LE)/liquid-condensed (LC) phase transition of dipalmitoyl phosphatidylcholine (DPPC) Langmuir monolayers. The formation of domains of an LC phase, which typically occurs in the LE/LC coexistence region upon compression of DPPC, is prevented when the atmosphere above the DPPC monolayer is saturated with a gFC. When contacted with gFC, the DPPC monolayer remains in the LE phase for surface pressures lower than 38 mN m−1, as assessed by compression isotherms and fluorescence microscopy (FM). Moreover, gFCs can induce the dissolution of preexisting LC phase domains and facilitate the respreading of the DPPC molecules on the water surface, as shown by FM and grazing incidence x-ray diffraction. gFCs have thus a highly effective fluidizing effect on the DPPC monolayer. This gFC-induced fluidizing effect was compared with the fluidizing effect brought about by a mixture of unsaturated lipids and proteins, namely the two commercially available lung surfactant substitutes, Curosurf and Survanta, which are derived from porcine and bovine lung extracts, respectively. The candidate FCs were chosen among those already investigated for biomedical applications, and in particular for intravascular oxygen transport, i.e., Perfluorooctyl Bromide, Perfluorooctylethane, bis(perfluorobutyl)ethene, perfluorodecalin, and perfluorooctane. The fluidizing effect is most effective with the linear FCs. This study suggests that FCs, whose biocompatibility is well documented, may be useful in lung surfactant substitute compositions.
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cosurfactant effect of a semifluorinated alkane at a fluorocarbon water interface impact on the stabilization of fluorocarbon in water emulsions
Langmuir, 2004Co-Authors: Sabina Marie Bertilla, Jeanlouis Thomas, Pascal Marie, Marie Pierre KrafftAbstract:Previous work has demonstrated that semifluorinated alkanes C n F 2 n + 1 C m H 2 m + 1 (FnHm diblocks), when used in conjunction with phospholipids, strongly stabilize fluorocarbon (FC)-in-water emulsions destined to be used as oxygen carriers. Although the presence of FnHm diblocks in the emulsion's interfacial phospholipid film was suggested to account for the observed stabilization, no direct proof of the diblock's location has been provided so far. We now report definite experimental evidence of the diblock's presence at the interfacial film, both on a macroscopic level by investigating the FC/water interface using the pendant drop method and directly on emulsions by monitoring their stability for various phospholipid chain lengths. We first establish that F8H16 has a strong cosurfactant effect with phospholipids [dimyristoylphosphatidylcholine (DMPC), dilaurylphosphatidylcholine (DLPC), dioctanoylphosphatidylcholine (PCL8)] at a Perfluorooctyl Bromide (PFOB)/water interface, as evidenced by a dramatic F8H16-concentration-dependent decrease of the interfacial tension. Where FC emulsions are concerned, we show that the stabilization effect, which consists of a decrease of the rate of molecular diffusion of the FC, depends strongly on the length of the phospholipid's fatty chain as compared to the length of the hydrocarbon segment, Hm, of the diblock. Stabilization is maximized when the Hm length is similar to that of the phospholipid's fatty chains. A strong mismatch between Hm and the phospholipid chain length can actually destabilize the emulsion. A different destabilization mechanism is then at work: coalescence. The presence of F8H16 at the interfacial film is further supported by the fact that perfluorodecyl Bromide, a heavy analogue of PFOB that stabilizes PFOB emulsions by lowering the solubility and diffusibility ofthe emulsion's dispersed FC phase, exercises its stabilizing effect similarly for all the phospholipids investigated.
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assay method for the Perfluorooctyl Bromide perflubron in rat blood by gas chromatography mass spectrometry
Journal of Chromatography B: Biomedical Sciences and Applications, 1999Co-Authors: Michel Audran, Marie Pierre Krafft, Jacques De Ceaurriz, Jeancharles Mathurin, Marietherese Sicart, Benedicte Marion, Fabien Fabre, Francoise BressolleAbstract:Abstract This paper describes a GC–MS method (SIM mode) for the analysis of Perfluorooctyl Bromide (perflubron, I ) in rat blood. The chromatographic separation was performed by injection in the split mode using a CP-select 624 CB capillary column. Following destruction of the emulsion by addition of ethanol, the analytical procedure involves a liquid–liquid extraction with 1,1,2-trichlorotrifluoroethane. The bis( F -butyl)ethene ( II) was used as internal standard. Observed retention times were 3.22 min for I and 2.32 min for II . Two calibration curves were used; linear detection responses were obtained for concentrations ranging from 0.009 to 0.9 mg/ml and from 0.9 to 13.5 mg/ml. The extraction efficiency averaged 50% for I and 93% for II . Precision ranged from 0.7 to 14%, and accuracy was between 91 and 109%. The limit of quantification was 9 μg/ml. The method validation results indicate that the performance characteristics of the method fulfilled the requirements for assay method for use in pharmacokinetic studies.
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aerobic preservation of organs using a new perflubron lecithin emulsion stabilized by molecular dowels
Journal of Surgical Research, 1996Co-Authors: Eric J Voiglio, Linda Zarif, F Gorry, Marie Pierre Krafft, J Margonari, Jean G Riess, X Martin, Jean-michel DubernardAbstract:The purpose of the study reported here was to explore a new strategy for the aerobic preservation of transplants using stable concentrated fluorocarbon emulsions as an oxygen delivery system. Fluorocarbons (FCs) are synthetic molecules, chemically and biologically inert, with a high oxygen-dissolving capacity. As they do not mix with water, it is necessary to emulsify them for intra-vascular use. Perfluorooctyl Bromide (or perflubron) can be emulsified with egg-yolk phospholipid (EYP), a nontoxic emulsifiant. The recent adjunction of amphiphilic fluorocarbon–hydrocarbon diblock molecules allows the obtaining of stable emulsions. By contrast with hemoglobin, fluorocarbons release oxygen following Henry's linear law rather than Barcroft's sigmoid curve. Release of oxygen by the FCs is only slightly influenced by temperature, which is an advantage for the preservation of organs. We tested a new 90% w/v fluorocarbon stem emulsion (perflubron/EYL/F6H10) diluted to 36% w/v with a hydroelectrolytic solution containing albumin, on four multiple organ blocks (MOBs; heart–lungs, liver, pancreas, kidneys, small intestine) of rats (EMOBs). Five control MOBs were perfused with a 50% v/v mixture of rat-blood and Krebs solution (KBMOBs). The lungs were ventilated with a FiO2 = 100%. In all cases the survival of the MOBs was greater than 210 min, with stable hemodynamics and preserved hydroelectrolytic and acid–base balances. The levels of lactate, amylase, and CK of the EMOBs were inferior (P< 0.05) to those of the KBMOBs between the first and the second hour. The diuresis of the EMOBs was higher (P< 0.05) than that of the KBMOBs (5.65 ± 1.76 vs 1.21 ± 0.28 mg/min). The production of bile, and the AST and ALT levels, were not significantly different. The PaO2 of the EMOBs was higher (P< 0.01) than for the KBMOBs. In normothermy, the maintenance of an aerobic metabolism using the FC emulsion caused less damage to the organs. Aerobic preservation of organs using FC emulsions therefore appears to be an attractive alternative to the presently used cold ischemia.
Sophie Houvenagel - One of the best experts on this subject based on the ideXlab platform.
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Comb-Like Fluorophilic-Lipophilic-Hydrophilic Polymers for Nanocapsules as Ultrasound Contrast Agents
Biomacromolecules, 2018Co-Authors: Sophie Houvenagel, Laurence Moine, Guilherme Picheth, Annie Brûlet, Alexis Chennevière, Vincent Faugeras, Camille Dejean, Olivier Couture, Nicolas Huang, Nicolas TsapisAbstract:Imaging the enhanced permeation and retention effect by ultrasound is hindered by the large size of commercial ultrasound contrast agents (UCAs). To obtain nanosized UCAs, triblock copolymers of poly(ethylene glycol)-polylactide-poly(1H,1H,2H,2H-heptadecafluorodecyl methacrylate) (PEG-PLA-PFMA) with distinct numbers of perfluorinated pendant chains (5, 10, or 20) are synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. Nanocapsules (NCs) containing Perfluorooctyl Bromide (PFOB) intended as UCAs are obtained with a 2-fold increase in PFOB encapsulation efficiency in fluorinated NCs as compared with plain PEG-PLA NCs thanks to fluorous interactions. NC morphology is strongly influenced by the number of perfluorinated chains and the amount of polymer used for formulation, leading to peculiar capsules with several PFOB cores at high PEG-PLA-PFMA 20 amount and single-cored NCs with a thinner shell at low fluorinated polymer amount, as confirmed by small-angle neutron scattering. Finally, fluorinated NCs yield higher in vitro ultrasound signal compared with PEG-PLA NCs, and no in vitro cytotoxicity is induced by fluorinated polymers and their degradation products. Our results highlight the benefit of adding comb-like fluorinated blocks in PEG-PLA polymers to modify the nanostructure and enhance the echogenicity of nanocapsules intended as UCAs.
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Comb-Like Fluorophilic-Lipophilic-Hydrophilic Polymers for Nanocapsules as Ultrasound Contrast Agents
Biomacromolecules, 2018Co-Authors: Sophie Houvenagel, Laurence Moine, Guilherme Picheth, Annie Brûlet, Alexis Chennevière, Vincent Faugeras, Camille Dejean, Olivier Couture, Nicolas Huang, Nicolas TsapisAbstract:© 2018 American Chemical Society. Imaging the enhanced permeation and retention effect by ultrasound is hindered by the large size of commercial ultrasound contrast agents (UCAs). To obtain nanosized UCAs, triblock copolymers of poly(ethylene glycol)-polylactide-poly(1H,1H,2H,2H-heptadecafluorodecyl methacrylate) (PEG-PLA-PFMA) with distinct numbers of perfluorinated pendant chains (5, 10, or 20) are synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. Nanocapsules (NCs) containing Perfluorooctyl Bromide (PFOB) intended as UCAs are obtained with a 2-fold increase in PFOB encapsulation efficiency in fluorinated NCs as compared with plain PEG-PLA NCs thanks to fluorous interactions. NC morphology is strongly influenced by the number of perfluorinated chains and the amount of polymer used for formulation, leading to peculiar capsules with several PFOB cores at high PEG-PLA-PFMA20amount and single-cored NCs with a thinner shell at low fluorinated polymer amount, as confirmed by small-angle neutron scattering. Finally, fluorinated NCs yield higher in vitro ultrasound signal compared with PEG-PLA NCs, and no in vitro cytotoxicity is induced by fluorinated polymers and their degradation products. Our results highlight the benefit of adding comb-like fluorinated blocks in PEG-PLA polymers to modify the nanostructure and enhance the echogenicity of nanocapsules intended as UCAs.
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Comb-Like Fluorophilic-Lipophilic-Hydrophilic Polymers for Nanocapsules as Ultrasound Contrast Agents
2018Co-Authors: Sophie Houvenagel, Laurence Moine, Guilherme Picheth, Vincent Faugeras, Camille Dejean, Olivier Couture, Nicolas Huang, Annie Brûlet, Alexis Chennevière, Nicolas TsapisAbstract:Imaging the enhanced permeation and retention effect by ultrasound is hindered by the large size of commercial ultrasound contrast agents (UCAs). To obtain nanosized UCAs, triblock copolymers of poly(ethylene glycol)-polylactide-poly(1H,1H,2H,2H-heptadecafluorodecyl methacrylate) (PEG-PLA-PFMA) with distinct numbers of perfluorinated pendant chains (5, 10, or 20) are synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. Nanocapsules (NCs) containing Perfluorooctyl Bromide (PFOB) intended as UCAs are obtained with a 2-fold increase in PFOB encapsulation efficiency in fluorinated NCs as compared with plain PEG-PLA NCs thanks to fluorous interactions. NC morphology is strongly influenced by the number of perfluorinated chains and the amount of polymer used for formulation, leading to peculiar capsules with several PFOB cores at high PEG-PLA-PFMA20 amount and single-cored NCs with a thinner shell at low fluorinated polymer amount, as confirmed by small-angle neutron scattering. Finally, fluorinated NCs yield higher in vitro ultrasound signal compared with PEG-PLA NCs, and no in vitro cytotoxicity is induced by fluorinated polymers and their degradation products. Our results highlight the benefit of adding comb-like fluorinated blocks in PEG-PLA polymers to modify the nanostructure and enhance the echogenicity of nanocapsules intended as UCAs
Bruce K. Rubin - One of the best experts on this subject based on the ideXlab platform.
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Effect of meconium on the surface properties of perflubron.
Pediatric Critical Care Medicine, 2004Co-Authors: Mamta Fuloria, Mary L. Brandt, Bruce K. RubinAbstract:OBJECTIVE Meconium passage with pulmonary aspiration in utero is associated with surfactant inactivation and is a major cause of neonatal morbidity and mortality. Ventilation with low surface tension perfluorocarbon in animal models of meconium aspiration has been shown to improve both oxygenation and lung compliance. Exogenously administered surfactant is inactivated by meconium. We wished to determine whether meconium would alter the surface properties of Perfluorooctyl Bromide (perflubron). DESIGN Biophysical analysis using novel methods. SETTING University research laboratory. SUBJECTS Healthy newborns. INTERVENTIONS First pass meconium was obtained from healthy newborns. MEASUREMENTS AND MAIN RESULTS We evaluated the surface-active properties of perflubron after exposure to meconium-saline dilutions using the de Nouy ring distraction technique to measure interfacial tension and the sessile contact angle of meconium-saline suspensions. Both were assessed in the absence and presence of perflubron. Meconium-saline suspensions inhibited surfactant activity. In contrast, the surface properties of perflubron were unaffected by the presence of meconium-saline suspensions. CONCLUSIONS These data are consistent with reported observations of increased lung compliance in perfluorocarbon-treated animals with meconium aspiration. In addition to these clinical implications, the novel interfacial tension technique described here could prove useful for assessing the interfacial properties of other poorly miscible biological fluids.
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Perfluorooctyl Bromide perflubron stimulates mucin secretion in the ferret trachea
Chest, 1999Co-Authors: Chikako Kishioka, Matthew P Dorighi, Bruce K. RubinAbstract:Objectives: Partial liquid ventilation with Perfluorooctyl Bromide (perflubron) has been shown to be safe and effective in animal models with respiratory failure. However, airway mucus accumulation has been reported to be a problem in human trials. We hypothesized that this might be because perflubron directly affects mucociliary clearance or stimulates mucus secretion. Methods and results: We first measured the mucociliary transportability of secretions on the mucus-depleted frog palate exposed to perflubron and demonstrated that the ciliated epithelium remained intact with preservation of mucociliary transport. We then measured mucin and lysozyme secretion from isolated ferret tracheal segments to evaluate the secretagogue potential of perflubron. There was an 86% increase in mucin secretion with perflubron incubation at 40 min (n 5 19; p < 0.01) and a 52% increase afte r4ho fexposure followed by evaporation of perflubron (n 5 19; p < 0.01). There was no significant difference in lysozyme secretion at any time between perflubronexposed or buffer-exposed tissue (n 5 4). The secretagogue effect was completely blocked by nordihydroguaiaretic acid, an inhibitor of arachidonic acid (AA) metabolism. Conclusion: These data suggest that although perflubron does not seem to be harmful to the airway, it induces mucus secretion in a noninflamed airway, and that this can be modulated by inhibitors of AA metabolism. (CHEST 1999; 115:823‐828)