Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research.

The specific properties of fluorocarbons, exceptional chemical and biological inertness, high gas-dissolving capacity, low surface tension, excellent spreading characteristics and high fluidity, have triggered numerous applications of these compounds in oxygen delivery. An injectable emulsion of fluorocarbon-in-water destined to deliver oxygen to tissues at risk of hypoxia has now completed Phase III clinical trials in Europe. A neat fluorocarbon is currently investigated in Phase II for treatment of acute respiratory failure by liquid ventilation. Fluorinated lipids and fluorinated surfactants can be used to elaborate and stabilize various colloidal systems, including different types of emulsions, vesicles and tubules, that also show promise for controlled release drug delivery.

[1]  A. Holzenburg,et al.  The potential of fluorinated surfactants in membrane biochemistry. , 1995, Analytical biochemistry.

[2]  A. Lattes,et al.  SYNTHESIS OF LONG CHAIN N-ALKYLLACTYLAHINES FROM UNPROTECTED LACTOSE A NEV SERIES OF NON-IONIC SURFACTANTS , 1991 .

[3]  F. Frézard,et al.  Novel liposome systems based on the incorporation of (perfluoroalkyl) alkenes (FmHnE) into the bilayer of phospholipid liposomes , 1994 .

[4]  S. Ristori,et al.  Magnetic Resonance Characterization of Betaine Micelles and Betaine−Perfluoropolyether Mixed Vesicles , 1997 .

[5]  S. Flaim.  Pharmacokinetics and side effects of perfluorocarbon-based blood substitutes. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[6]  P. Mukerjee.  Fluorocarbon—hydrocarbon interactions in micelles and other lipid assemblies, at interfaces, and in solutions , 1994 .

[7]  J. Greiner,et al.  Vesicles made of glycophospholipids with homogeneous (two fluorocarbon or two hydrocarbon) or heterogeneous (one fluorocarbon and one hydrocarbon) hydrophobic double chains. , 1996, Biochimica et biophysica acta.

[8]  P. Menasché,et al.  Fluorocarbons: a potential treatment of cerebral air embolism in open-heart surgery. , 1985, The Annals of thoracic surgery.

[9]  J. Riess,et al.  Stable Highly Concentrated Fluorocarbon Gels , 1994 .

[10]  J. Riess.  Fluorocarbon‐Based in vivo Oxygen Transport and Delivery Systems , 1991, Vox sanguinis.

[11]  H. Ringsdorf,et al.  Structural studies of polymers with hydrophilic spacer groups. 2. Infrared spectroscopy of Langmuir-Blodgett multilayers of polymers with fluorocarbon side chains at ambient and elevated temperatures , 1989 .

[12]  K. J. Mysels,et al.  Anomalies of Partially Fluorinated Surfactant Micelles , 1975 .

[13]  M. Volkenstein,et al.  Statistical mechanics of chain molecules , 1969 .

[14]  N. Hsia,et al.  The toxicities of native and modified hemoglobins. , 1997, Free radical biology & medicine.

[15]  B. Pucci,et al.  New perfluoroalkyl telomeric non-ionic surfactants : synthesis, physicochemical and biological properties , 1992 .

[16]  D. L. Parsons,et al.  Perfluorochemical erythrocyte substitutes: disposition and effects on drug distribution and elimination. , 1991, Drug metabolism reviews.

[17]  Thomas H. Shaffer,et al.  Partial Liquid Ventilation with Perflubron in Premature Infants with Severe Respiratory Distress Syndrome , 1996 .

[18]  P. Vierling,et al.  Permeability and stability in buffer and in human serum of fluorinated phospholipid-based liposomes. , 1994, Biochimica et biophysica acta.

[19]  Charles Tanford,et al.  The Hydrophobic Effect: formation of micelles and biological membranes''John Wiley & Sons , 1991 .

[20]  R. Twieg,et al.  Structural studies of semifluorinated n-alkanes. 1. Synthesis and characterization of F(CF2)n(CH2)mH in the solid state , 1984 .

[21]  J. Riess,et al.  Fluorinated phosphocholine-based amphiphiles as components of fluorocarbon emulsions and fluorinated vesicles , 1995 .

[22]  T. Kunitake,et al.  Formation and Enhanced Stability of Fluoroalkyl Bilayer Membranes , 1982 .

[23]  F. A. Ubel,et al.  Health status of plant workers exposed to fluorochemicals--a preliminary report. , 1980, American Industrial Hygiene Association journal.

[24]  G. Mathis,et al.  A NOVEL CLASS OF NONIONIC MICROEMULSIONS: FLUOROCARBONS IN AQUEOUS SOLUTIONS OF FLUORINATED POLY(OXYETHYLENE) SURFACTANTS , 1984 .

[25]  H. Fraaije,et al.  Functionalized lipid tubules: A tool for helical crystallization of proteins , 1997 .

[26]  E. Beckman,et al.  Affinity Extraction into Carbon Dioxide. 1. Extraction of Avidin Using a Biotin-Functional Fluoroether Surfactant , 1997 .

[27]  P. Mukerjee,et al.  Adsorption of fluorocarbon and hydrocarbon surfactants to air-water, hexane-water and perfluorohexane-water interfaces. Relative affinities and fluorocarbon-hydrocarbon nonideality effects , 1981 .

[28]  J. Greiner,et al.  ANIONIC GLUCOPHOSPHOLIPIDS: A NEW FAMILY OF TUBULE-FORMING AMPHIPHILES , 1996 .

[29]  E. O’Rear,et al.  Unusual micellar properties of a new class of fluorinated nonionic surfactants , 1988 .

[30]  F. Frézard,et al.  Incorporation of a perfluoroalkylalkane (RFRH) into the phospholipid bilayer of dmpc liposomes results in greater encapsulation stability , 1994 .

[31]  M. Welte,et al.  Perflubron emulsion delays blood transfusions in orthopedic surgery. European Perflubron Emulsion Study Group. , 1999, Anesthesiology.

[32]  P. Keipert,et al.  Randomized Safety Studies of Intravenous Perflubron Emulsion. II. Effects on Immune Function in Healthy Volunteers , 2000 .

[33]  I. Rico-Lattes,et al.  Microemulsions of perfluorinated and semi-fluorinated compounds. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[34]  A. Fraire,et al.  Partial Liquid Ventilation with Perfluorocarbon in the Treatment of Rats with Lethal Pneumococcal Pneumonia , 1998, Anesthesiology.

[35]  A. Veyre,et al.  Disposition in rat of a new fluorinated, biocompatible, non-ionic telomeric carrier. , 1994, Xenobiotica; the fate of foreign compounds in biological systems.

[36]  J. Schnur,et al.  Lipid Tubules: A Paradigm for Molecularly Engineered Structures , 1993, Science.

[37]  A. Knoblich,et al.  The use of semifluorinated alkanes in blood-substitutes. , 1993, Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology.

[38]  W. Fox,et al.  Pulmonary administration of gentamicin during liquid ventilation in a newborn lamb lung injury model. , 1997, Pediatrics.

[39]  N. Brace.  Free-radical addition of iodoperfluoralkanes to terminal alkadienes. Relative reactivity as a function of chain length and reaction conditions , 1973 .

[40]  J. Riess,et al.  Hydrolysis of DMPC or DPPC by pancreatic phospholipase A2 is slowed down when (perfluoroalkyl) alkanes are incorporated into the liposomal membrane. , 1995, Biochimica et biophysica acta.

[41]  R. Twieg,et al.  Observations of a gel phase in binary mixtures of semifluorinated n-alkanes with hydrocarbon liquids , 1985 .

[42]  B. Teicher,et al.  An overview on oxygen carriers in cancer therapy. , 1995, Artificial cells, blood substitutes, and immobilization biotechnology.

[43]  P. Vierling,et al.  Phase behavior of fluorocarbon di-O-alkyl-glycerophosphocholines and glycerophosphoethanolamines and long-term shelf stability of fluorinated liposomes. , 1997, Biochimica et biophysica acta.

[44]  C. Tondre,et al.  Solubilization of water in binary mixtures of fluorocarbons and nonionic fluorinated surfactants: existence domains of reverse microemulsions , 1984 .

[45]  J. Holmes,et al.  Bioconversions in a Water-in-CO2 Microemulsion , 1998 .

[46]  J. Greiner,et al.  Carbohydrate- and related polyol-derived fluorosurfactants: an update. , 2000, Carbohydrate research.

[47]  Shlomo Magdassi,et al.  Interactions between collagen and perfluorocarbon emulsions , 1992 .

[48]  M. J. Rosen.  Surfactants and Interfacial Phenomena , 1978 .

[49]  L. C. Clark,et al.  Response of the rabbit lung as a criterion of safety for fluorocarbon breathing and blood substitutes. , 1992, Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology.

[50]  F. Candau,et al.  Multicompartment Polymeric Micelles Based on Hydrocarbon and Fluorocarbon Polymerizable Surfactants , 1999 .

[51]  S. Benita.  Submicron Emulsions in Drug Targeting and Delivery , 2019 .

[52]  L. C. Clark,et al.  Some morphologic effects of "inert" particulate loading on hemopoietic elements in mice. , 1976, Journal of the Reticuloendothelial Society.

[53]  R. Mattrey.  The potential role of perfluorochemicals (PFCs) in diagnostic imaging. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[54]  H Permadi,et al.  Effects of perfluoro fatty acids on xenobiotic-metabolizing enzymes, enzymes which detoxify reactive forms of oxygen and lipid peroxidation in mouse liver. , 1992, Biochemical pharmacology.

[55]  Frank V. Bright,et al.  Water-in-Carbon Dioxide Microemulsions: An Environment for Hydrophiles Including Proteins , 1996, Science.

[56]  K. Shinoda,et al.  Physicochemical properties of aqueous solutions of fluorinated surfactants , 1972 .

[57]  R. Enick,et al.  The phase behavior and gel formation of binary mixtures of carbon dioxide and semifluorinated alkanes , 1991 .

[58]  J. Riess.  Chapter 23 – Fluorocarbon emulsions—Designing an efficient shuttle service for the respiratory gases—The so-called ‘Blood Substitutes’ , 2000 .

[59]  Y. Ishikawa,et al.  Self-Organization of Solvophobic, Double-Chained Fluorocarbon Derivatives in Organic Media , 1989 .

[60]  E. Beckman.  Carbon Dioxide Extraction of Biomolecules , 1996, Science.

[61]  N. S. Faithfull,et al.  The Role of Perfluorochemicals in Surgery and the ITU , 1994 .

[62]  J. Riess,et al.  Influence of the 100% w/v perfluorooctyl bromide (PFOB) emulsion dose on tumour radiosensitivity. , 1991, International journal of radiation biology.

[63]  T. Uchida,et al.  Treatment of Pulmonary Hypertension and Hypoxia Due to Oleic Acid Induced Lung Injury with Intratracheal Prostaglandin E1 during Partial Liquid Ventilation , 1998, Anesthesiology.

[64]  J. Riess,et al.  Reassessment of criteria for the selection of perfluorochemicals for second-generation blood substitutes: analysis of structure/property relationships. , 1984, Artificial organs.

[65]  P. Vierling,et al.  Highly Stable Liposomes Derived from Perfluoroalkylated Glycerophosphocholines , 1991 .

[66]  J. Riess,et al.  Chapter 7 – Update on Perfluorocarbon-Based Oxygen Delivery Systems , 1998 .

[67]  L. Zarif,et al.  Design, synthesis and evaluation of fluorocarbons and surfactants for in vivo applications. New perfluoroalkylated polyhydroxylated surfactants. , 1988, Biomaterials, artificial cells, and artificial organs.

[68]  J. Riess,et al.  Can Single‐Chain Perfluoroalkylated Amphiphiles Alone Form Vesicles and Other Organized Supramolecular Systems? , 1993 .

[69]  H. Ohyanagi,et al.  Fate of perfluorochemicals in animals after intravenous injection or hemodilution with their emulsions. , 1978, Chemical & pharmaceutical bulletin.

[70]  M. Winnik,et al.  Flowable networks as DNA sequencing media in capillary columns , 1996, Electrophoresis.

[71]  J. Riess,et al.  Micellization and Adsorption of Fluorinated Amphiphiles: Questioning the 1 CF2≈1.5 CH2 Rule , 1998 .

[72]  P. Vierling,et al.  Extended in vivo blood circulation time of fluorinated liposomes , 1993, FEBS letters.

[73]  J. Ravey,et al.  Structure of inverse micelles and emulsion-gels with fluorinated nonionic surfactants. A small-angle neutron scattering study , 1990 .

[74]  M. Infante,et al.  Nonionic amphiphilic compounds from aspartic and glutamic acids as structural mimics of lecithins , 1996 .

[75]  W. Richtering,et al.  Melting, crystallization, and solution behavior of chain molecules with hydrocarbon and fluorocarbon segments , 1988 .

[76]  J. Riess,et al.  Highly fluorinated amphiphiles and colloidal systems, and their applications in the biomedical field. A contribution. , 1998, Biochimie.

[77]  W. Reilly.  Novel Cosmetic Delivery Systems , 2000 .

[78]  R. Filler,et al.  Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications , 1993 .

[79]  Y. Ishikawa,et al.  Self-assembly of bilayers from double-chain fluorocarbon amphiphiles in aprotic organic solvents: thermodynamic origin and generalization of the bilayer assembly , 1994 .

[80]  P. Keipert,et al.  Proposed mechanism of pulmonary gas trapping (PGT) following intravenous perfluorocarbon emulsion administration. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[81]  D. Liggitt,et al.  Perflubron enhances adenovirus-mediated gene expression in lungs of transgenic mice with chronic alveolar filling. , 1999, Human gene therapy.

[82]  F. Lederer,et al.  Perfluoroalkylphosphocholines are poor protein-solubilizing surfactants, as tested with neutrophil plasma membranes. , 1998, Biochimie.

[83]  H. Hoffmann,et al.  Small angle neutron scattering measurements on micellar solutions of perfluor detergents , 1983 .

[84]  C. Sirlin,et al.  Gene transfer with a series of lipophilic DNA-binding molecules. , 1994, Bioconjugate chemistry.

[85]  J. G. Riess,et al.  Solubility and transport phenomena in perfluorochemicals relevant to blood substitution and other biomedical applications , 1982 .

[86]  R. Dechert,et al.  Liquid ventilation in adults, children, and full-term neonates , 1995, The Lancet.

[87]  G. Mathis,et al.  Synthesis of homogeneous polyoxyethylene perfluorcalkyl surfactants , 1983 .

[88]  P. Vierling,et al.  Polymorphic phase behavior of perfluoroalkylated phosphatidylcholines. , 1994, Biochimica et biophysica acta.

[89]  土田 英俊.  Blood substitutes : present and future perspectives , 1998 .

[90]  C. Jaffe,et al.  Reduction of myocardial ischemia during percutaneous transluminal coronary angioplasty with oxygenated Fluosol. , 1990, The American journal of cardiology.

[91]  J. Riess.  Highly fluorinated systems for oxygen transport, diagnosis and drug delivery , 1994 .

[92]  H. Ohyanagi,et al.  Discussion and considerations for the excretion mechanism of perfluorochemical emulsion. , 1988, Biomaterials Artificial Cells and Artificial Organs.

[93]  L. Zarif,et al.  Novel fluorocarbon-based injectable oxygen-carrying formulations with long-term room-temperature storage stability. , 1994, Advances in experimental medicine and biology.

[94]  B. Pucci,et al.  Vesicles and other supramolecular systems from biocompatible synthetic glycolipids with hydrocarbon and/or fluorocarbon chains. , 1994, Chemistry and physics of lipids.

[95]  Dorian A. Canelas,et al.  Design of Nonionic Surfactants for Supercritical Carbon Dioxide , 1996, Science.

[96]  J. Riess,et al.  Stable Flexible Fibers and Rigid Tubules Made from Single‐Chain Perfluoroalkylated Amphiphiles , 1994 .

[97]  C. Bunn,et al.  A Room-Temperature Transition in Polytetrafluoroethylene , 1949, Nature.

[98]  J. Riess,et al.  Perfluoroalkylated amphiphiles with a morpholinophosphate or a dimorpholinophosphate polar head group , 1998 .

[99]  B. Ninham,et al.  Theory of self-assembly of lipid bilayers and vesicles. , 1977, Biochimica et biophysica acta.

[100]  H. Eicke.  Modern Trends of Colloid Science in Chemistry and Biology , 1985 .

[101]  K. Shinoda,et al.  Krafft points, critical micelle concentrations, surface tension, and solubilizing power of aqueous solutions of fluorinated surfactants , 1976 .

[102]  A. Chittofrati,et al.  Perfluoropolyether microemulsions: Conductivity behavior of three-component W/O systems , 1992 .

[103]  J. Ravey,et al.  Phase and structure behaviour of fluorinated nonionic surfactant systems , 1987 .

[104]  A. Rotta,et al.  Partial liquid ventilation: A multifaceted approach to acute respiratory distress syndrome , 1999 .

[105]  B. Pucci,et al.  Alkyl and perfluoroalkyl glycolipid-based supramolecular assemblies , 1994 .

[106]  Tada,et al.  Small-Angle Scattering and Electron Microscopy Investigation of Nanotubules Made from a Perfluoroalkylated Glucophospholipid. , 1999, Journal of colloid and interface science.

[107]  P. Vierling,et al.  Fluorinated phosphatidylcholine-based liposomes: H+/Na+ permeability, active doxorubicin encapsulation and stability, in human serum. , 1994, Biochimica et biophysica acta.

[108]  J. Riess,et al.  Highly effective surfactants with low hemolytic activity , 1991 .

[109]  E. Kaler,et al.  Microemulsifying fluorinated oils with mixtures of fluorinated and hydrogenated surfactants , 1994 .

[110]  H. Ringsdorf,et al.  Saturated and polymerizable amphiphiles with fluorocarbon chains. Investigation in monolayers and liposomes , 1984 .

[111]  M. Stébé,et al.  Release of a model molecule from highly concentrated fluorinated reverse emulsions. Influence of composition variables and temperature. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[112]  J. Ravey,et al.  Water in fluorocarbon gel emulsions : structures and rheology , 1994 .

[113]  E. Kissa.  Fluorinated surfactants : synthesis, properties, applications , 1994 .

[114]  W. Helfrich,et al.  Fluid and Solid Fibers Made of Lipid Molecular Bilayers , 1993 .

[115]  J. Brady,et al.  Semifluorinated hydrocarbons: primitive surfactant molecules , 1988 .

[116]  Self-organization of single-chain fluorinated amphiphiles with fluorinated alcohols , 1996 .

[117]  T. Reed.  CHAPTER 2 – Physical Chemistry of Fluorocarbons , 1964 .

[118]  C. Lowe,et al.  Novel affinity separations based on perfluorocarbon emulsions: Use of a perfluorocarbon affinity emulsion for the direct extraction of glucose-6-phosphate dehydrogenase from homogenised bakers' yeast , 1994 .

[119]  T. A. Brown,et al.  Micelles and aggregates of fluorinated surfactants , 1991 .

[120]  J. V. Vanden Heuvel,et al.  Tissue distribution, metabolism, and elimination of perfluorooctanoic acid in male and female rats. , 1991, Journal of biochemical toxicology.

[121]  J. Ravey,et al.  Comparative study of fluorinated and hydrogenated nonionic surfactants. I. Surface activity properties and critical concentrations , 1988 .

[122]  A. Knoblich,et al.  On the perfluorocarbon emulsions of second generation. , 1992, Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology.

[123]  A. Lattes,et al.  Synthesis of new fluorinated non-ionic surfactants derived from lactose: the N-[2-(F-alkyl)ethyl]-lactosylamines and -lactobionamides , 1992 .

[124]  M E Andersen,et al.  The acute toxicity of perfluorooctanoic and perfluorodecanoic acids in male rats and effects on tissue fatty acids. , 1983, Toxicology and applied pharmacology.

[125]  J. Popot,et al.  Stabilization of integral membrane proteins in aqueous solution using fluorinated surfactants. , 1998, Biochimie.

[126]  C. Mioskowski,et al.  Synthesis and preliminary evaluation of a new class of fluorinated amphiphiles designed for in-plane immobilisation of biological macromolecules , 1997 .

[127]  D. Gruen.  A model for the chains in amphiphilic aggregates. 2. Thermodynamic and experimental comparisons for aggregates of different shape and size , 1985 .

[128]  T. Shaffer,et al.  Enhanced distribution of adenovirus-mediated gene transfer to lung parenchyma by perfluorochemical liquid. , 1997, Human gene therapy.

[129]  B. Smart,et al.  Are fluorocarbon chains stiffer than hydrocarbon chains? Dynamics of end-to-end cyclization in a C8F16 segment monitored by fluorescence , 1990 .

[130]  M R Wolfson,et al.  Comparison of gas and liquid ventilation: clinical, physiological, and histological correlates. , 1992, Journal of applied physiology.

[131]  S. Rockwell.  Perfluorochemical emulsions and radiation therapy. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[132]  J. Vincent,et al.  Yearbook of Intensive Care and Emergency Medicine , 1995, Yearbook of Intensive Care and Emergency Medicine.

[133]  M. Verani,et al.  Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction. , 1991, Journal of the American College of Cardiology.

[134]  W. Holman,et al.  Tissue oxygenation with graded dissolved oxygen delivery during cardiopulmonary bypass. , 1995, The Journal of thoracic and cardiovascular surgery.

[135]  Jean G. Riess,et al.  Fluorocarbons and Fluorosurfactants for In Vivo Oxygen Transport (Blood Substitutes), Imaging, and Drug Delivery , 1999 .

[136]  Y. Ishikawa,et al.  Self-Organization of Bilayer Assemblies in a Fluorocarbon Medium , 1993 .

[137]  L. Zarif,et al.  Novel injectable fluorinated contrast agents with enhanced radiopacity. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[138]  D. Klein,et al.  Recent developments in pharmacokinetic modeling of perfluorocarbon emulsions. , 1996, Artificial cells, blood substitutes, and immobilization biotechnology.

[139]  M. Wolfson,et al.  Pulmonary administration of vasoactive substances by perfluorochemical ventilation. , 1996, Pediatrics.

[140]  H. Watzke,et al.  New Synthetic Strategy to Vesicle‐Forming Perfluoroalkylated Amphiphiles. , 1995 .

[141]  A. Bondi.  van der Waals Volumes and Radii , 1964 .

[142]  P. Menasché,et al.  1985: Fluorocarbons: a potential treatment of cerebral air embolism in open-heart surgery. 1992 update. , 1992, The Annals of thoracic surgery.

[143]  C. Haisch,et al.  The feasibility of organ preservation at warmer temperatures. , 1996, Transplantation Proceedings.

[144]  G. Tiddy.  Concentrated Surfactant Systems , 1985 .

[145]  Luis Solé-Violan,et al.  A NEW CONCEPT IN THE STABILIZATION OF INJECTABLE FLUOROCARBON EMULSIONS: THE USE OF MIXED FLUOROCARBON-HYDROCARBON DOWELS. , 1992 .

[146]  J. Riess,et al.  Improved control over particle sizes and stability of concentrated fluorocarbon emulsions by using mixed fluorocarbon/hydrocarbon molecular dowels. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[147]  Takayoshi Matsumoto,et al.  Fibril-vesicle transition and their structures — investigation by microscopy and small-angle scattering , 1997 .

[148]  P. Luisi,et al.  Lecithin organogel as matrix for transdermal transport of drugs. , 1992, Journal of pharmaceutical sciences.

[149]  Armand Lattes,et al.  Synthesis of new sugar-based surfactants having biological applications: key role of their self-association , 1997 .