Small particles of fusinite and carbohydrate chars coated with aqueous soluble polymers: preparation and applications for in vivo EPR oximetry.
The development of oxygen-sensitive paramagnetic materials is being pursued actively because of their potential applications in in vivo EPR oximetry. Among these materials, several charcoals and carbohydrate chars are of special interest because of their desirable EPR properties: high sensitivity of the EPR linewidth to the partial pressure of oxygen, simple EPR spectra, and high spin density. Their potential use in humans, however, is limited by the need to demonstrate that they will not lead to deleterious effects. A strategy was used to optimize the biocompatibility of the oxygen-sensitive materials by decreasing the size of the particles and coating them with suspending or surfactive agents such as arabic gum, poloxamer (Pluriol 6800), and polyvinylpyrrolidone. The coated particles of a carbohydrate char and fusinite were characterized in vitro for their size, stability, and pO2 sensitivity. The feasibility of performing pO2 measurement was examined in vivo by inducing ischemia in the gastrocnemius muscle of mice. The use of arabic gum for coating the fusinite particles preserved the pO2 sensitivity in vivo, whereas the other surfactive agents led to a loss of the pO2 sensitivity in vivo. Small particles of fusinite coated by arabic gum and intravenously administered to mice accumulated in the liver, whereas the uncoated fusinite was toxic when injected intravenously due to the large size and aggregation of the particles. Histological studies performed up to 6 months after the injection in muscles of mice did not indicate any toxicity from the materials used in the present study.
Gallez
B
B
Laboratory of Medicinal Chemistry and Radiopharmacy, University of Louvain, Brussels, Belgium.
Debuyst
R
R
Dejehet
F
F
Liu
K J
KJ
Walczak
T
T
Goda
F
F
Demeure
R
R
Taper
H
H
Swartz
H M
HM
D000818:Animals; D001672:Biocompatible Materials / Q000032:analysis / Q000633:toxicity; D002138:Calibration; D002244:Carbon / Q000032:analysis / Q000633:toxicity; D002606:Charcoal; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D007089:Image Enhancement / Q000379:methods*; D007275:Injections, Intravenous; D007511:Ischemia / Q000175:diagnosis*; D008099:Liver / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis*; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D015335:Molecular Probes / Q000032:analysis / Q000633:toxicity; D009132:Muscles / Q000098:blood supply* / Q000473:pathology; D010092:Oximetry / Q000379:methods*; D010316:Particle Size; D012995:Solubility; D013501:Surface-Active Agents
D001672:Biocompatible Materials; D015335:Molecular Probes; D013501:Surface-Active Agents; C091644:fusinite; D002606:Charcoal; D002244:Carbon