Synthesis, characterization and in vitro cytotoxicity studies of a macromolecular conjugate of paclitaxel bearing oxytocin as targeting moiety.
The present study describes the experimental synthetic procedure and the characterization of a new polyaspartamide macromolecular prodrug of paclitaxel, bearing oxytocin residues as targeting moieties. In vitro stability studies of bioconjugate, performed in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma, evidenced the high stability of the targeting portion (oxytocin)-polymer linkage and the ability of this conjugate to release linked paclitaxel in a prolonged way in plasma. Moreover, preliminary in vitro antiproliferative studies, carried out on MCF-7 cells, that are oxytocin receptor positive cells, showed that the polymeric conjugate has the same cell growing inhibition ability of free drug.
Cavallaro
Gennara
G
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Palermo, Italy. gennacav@unipa.it
Maniscalco
Laura
L
Campisi
Monica
M
Schillaci
Domenico
D
Giammona
Gaetano
G
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D015394:Molecular Structure; D010121:Oxytocin / Q000031:analogs & derivatives / Q000097:blood / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000097:blood / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018045:Receptors, Oxytocin / Q000378:metabolism; D012995:Solubility; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010455:Peptides; D011355:Prodrugs; D018045:Receptors, Oxytocin; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); D011092:Polyethylene Glycols; D010121:Oxytocin; D017239:Paclitaxel