Design and Synthesis of Phagocytosis-Resistant Polymeric Surfactants for the Development of Perfluorocarbon Emulsions

University Of Southern California, Los Angeles CA

Investigators

Abstract

0003006 Peng The synthesis is proposed of fluorine-containing polymeric (PPF) surfactants for the emulsification of perfluorocarbon chemicals (PFCs) that are useful as intravenous transfusion agents. Such emulsions are of interest as bioacceptable oxygen and carbon dioxide carriers that are less immunologic than is presently the case with the currently used Pluronic F-68 (polyoxyethylene polyoxypropylene block polymer) and egg yolk phospholipids (EYP). The PIs present evidence indicating that phagocytosis of PFC emulsion microparticles in the present of PPF surfactants is reduced compared to that by emulsions mediated by low molecular weight perfluorocarbon surfactants. The synthesis is proposed of two types of biocompatible hydrophilic polymers that have perfluorocarbon (RF) groups at the chain end or as pendent groups. The PIs outline procedures allowing the synthesis of such PPF surfactants with RF groups having between 4 and 12 carbons and hydrocarbon segment that allows varying degreds of hydrophobic/ lipophilic character. The hydrophlic polymers include polyethylene glycol (PEG), hydroxyethylcellulose (HEC), polyvinylpyrrolidone (PVP), and similar polymers. The polymers are synthesized either by chemical derivatization of the polymer end- or pendent group or by copolymerization of the water-soluble vinyl monomer(s) with RF-acrylates, -acrylamides or similar monomers. The polymers may also contain negatively charged groups that are anticipated to affect phagocytosis and/or PFC recognition by the immune system. The effect(s) of these PPF surfactants on the phagocytosis process will be investigated by a number of techniques that include optical and electron microscopy as well as fluorine-19 NMR. The PIs will also examine the rate of cytokine (e.g., IL-1b and TNF-a) secretion associated with the PFC emulsion droplets phagocytosed by J774A.1 macrophage cells. The efficiency of oxygen diffusion through the cell-PPF surfactant will be studied by oxygen microsensors.