Anti-cancer drug diffusion within living rat brain tissue: an experimental study using [3H](6)-5-fluorouracil-loaded PLGA microspheres.
This study was performed (i) to monitor the diffusion of the anti-cancer drug 5-fluorouracil (5-FU) and (ii) to elucidate the fate of poly(lactide-co-glycolide) (PLGA) based microspheres within living rat brain tissue upon intracranial implantation. Drug-loaded microparticles were prepared using a solvent emulsion/extraction process and administered into healthy and C6 glioma-bearing Sprague-Dawley rats. The same surgical procedure was carried out with magnetite-loaded microspheres. To monitor 5-FU diffusion from the implantation site, tissue combustion was performed on animals implanted with tritiated drug microspheres. T2-weighted nuclear magnetic resonance imaging was undertaken on animals implanted with magnetite-loaded microspheres to determine microsphere localization after deposit. Results show that an important microparticle backflow occurs in healthy rats, whereas the microspheres remain at the site of administration in C6 glioma-bearing rats. Drug diffusion is limited to the vicinity of the implantation site.
Roullin
Valérie Gaëlle
VG
INSERM ERIT-M 0104, Angers, France.
Deverre
Jean-Robert
JR
Lemaire
Laurent
L
Hindré
François
F
Venier-Julienne
Marie-Claire
MC
Vienet
Raymond
R
Benoit
Jean-Pierre
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism; D003287:Contrast Media / Q000493:pharmacokinetics; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D052203:Ferrosoferric Oxide; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005910:Glioma / Q000378:metabolism; D007267:Injections; D007501:Iron / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008863:Microspheres; D009368:Neoplasm Transplantation; D010087:Oxides / Q000493:pharmacokinetics; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003287:Contrast Media; D004337:Drug Carriers; D010087:Oxides; D011108:Polymers; D014316:Tritium; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007501:Iron; D005472:Fluorouracil; D052203:Ferrosoferric Oxide