Peptide-vector strategy bypasses P-glycoprotein efflux, and enhances brain transport and solubility of paclitaxel.
We present the results obtained with paclitaxel coupled to a peptide-vector SynB3 (PAX-OSUC-SynB3), showing that this peptide-vector enhances the solubility of paclitaxel and its brain uptake in mice using the in situ brain perfusion model. We also show by the in situ brain perfusion in P-glycoprotein (P-gp)-deficient and wild-type mice that vectorized paclitaxel bypasses the P-gp present at the luminal side of the blood-brain barrier. The effect of the vectorized paclitaxel on various cancer cells was not significantly different from that of free paclitaxel. These results indicate that vectorization of paclitaxel may have significant potential for the treatment of brain tumors.
Blanc
Emmanuelle
E
Synt:em, Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, Montpellier, France.
Bonnafous
Cécile
C
Merida
Peggy
P
Cisternino
Salvatore
S
Clair
Philippe
P
Scherrmann
Jean-Michel
JM
Temsamani
Jamal
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004337:Drug Carriers; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D012995:Solubility; D019802:Succinic Acid / Q000737:chemistry
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D009842:Oligopeptides; C501559:SynB3 peptide; D019802:Succinic Acid; D017239:Paclitaxel