Fluorocarbons and Fluorosurfactants for In Vivo Oxygen Transport (Blood Substitutes), Imaging, and Drug Delivery

The development of biomaterials to treat, repair, or reconstruct the human body is an increasingly important component of materials research. Collaboration between materials researchers and their industrial and clinical partners is essential for the development of this complex field. To demonstrate the importance of these interactions, two articles in this issue focus on advances in biomaterials relating to the use of colloidal systems for transport, drug delivery, and other medical applications. These articles were coordinated by Dominique Muster (Universite Louis Pasteur, Strasbourg) and Franz Burny (Hopital Erasme, Brussels). The following is the first of these two articles . A large variety of colloidal Systems involving highly fluorinated components have been prepared and investigated in recent years. These fluorinated Systems comprise diverse ty pes of emulsions (e.g., direct, reverse, and multiple emulsions; microemulsions; gel emulsions; waterless emulsions) with a fluorocarbon phase (and often a fluorinated Surfactant), and a range of self-assemblies (vesicles, tubules, helices, ribbons, etc.) made from fluorinated amphiphiles. Fluorinated Langmuir films and fluorinated black lipid membranes (BLMs) also have been investigated. Research in this area was driven by the potential applications of such materials in medicine and biology. Fluorocarbon-based products are being developed as injectable oxygen carriers (“blood Substitutes”), media for liquid Ventilation, drug delivery Systems, and contrast agents for ultrasound imaging. One such agent has recently been approved for use in Europe and the United States. Several more products are in an advanced stage of clinical evaluation, and others are in various stages of preclinical development. From a more fundamental Standpoint, these materials are being investigated for assessing and understanding the impact that fluorinated components have on the formation, stability, structure, and properties of colloida l Systems in comparison with their hydrocarbon counterparts. The attention given to fluorinated colloids prompted the synthesis of numerous new families of fluorinated amphiphiles, which were to become components of such colloids.

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

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

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

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

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

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

[7]  J. Ries DU FLUOR DANS NOS ARTERES , 1995 .

[8]  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 .

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

[10]  P. Nassoy,et al.  Search for perfectly ordered dense monolayers , 1993 .

[11]  D S Segar,et al.  Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial. , 1998, Journal of the American College of Cardiology.

[12]  B. Smart,et al.  Organofluorine chemistry : principles and commercial applications , 1994 .

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

[14]  T. Zuck Difficulties in demonstrating efficacy of blood substitutes. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[15]  R. Twieg,et al.  Structural characterization of semifluorinated n-alkanes. 2. Solid-solid transition behavior , 1986 .

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

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

[18]  J. Wahr,et al.  PERFLUBRON EMULSION IS MORE EFFECTIVE THAN BLOOD FOR TRANSFUSION TRIGGER REVERSAL , 1998 .

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

[20]  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.

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

[22]  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.

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

[24]  S. Rice,et al.  Structural transitions in a monolayer of fluorinated amphiphile molecules , 1992 .

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

[26]  G. L. Gaines Surface activity of semifluorinated alkanes : F(CF2)m(Ch2)nH , 1991 .

[27]  K. Lowe,et al.  Strategies for promoting division of cultured plant protoplasts : beneficial effects of oxygenated perfluorocarbon , 1995 .

[28]  J. Weers,et al.  Room temperature stable perfluorocarbon emulsions with acceptable half-lives in the reticuloendothelial system. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

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

[30]  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.

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

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

[33]  M. Wolfson,et al.  Perfluorochemical liquid as a respiratory medium. , 1994, Artificial cells, blood substitutes, and immobilization biotechnology.

[34]  J. Riess Introducing a new Element - Fluorine -Into the Liposomal Membrane , 1995 .

[35]  J. Riess,et al.  Fluorinated materials for in vivo oxygen transport (blood substitutes), diagnosis and drug delivery. , 1998, Biomaterials.

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

[37]  T. Shaffer,et al.  Liquid-assisted ventilation: physiology and clinical application. , 1997, Annals of medicine.

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

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

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

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

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

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

[44]  P. Keipert,et al.  Supporting tissue oxygenation during acute surgical bleeding using a perfluorochemical-based oxygen carrier. , 1996, Advances in experimental medicine and biology.

[45]  T. Kunitake,et al.  Synthetic Bilayer Membranes: Molecular Design, Self‐Organization, and Application , 1992 .

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

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

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

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

[50]  Zuck Tf,et al.  Current status of injectable oxygen carriers. , 1994 .

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

[52]  J. Riess,et al.  Achieving Stable, Reverse Water‐in‐Fluorocarbon Emulsions , 1996 .

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

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