title: Gemcitabine-loaded PEGylated unilamellar liposomes vs GEMZAR: biodistribution, pharmacokinetic features and in vivo antitumor activity.
abstract: The systemic efficacy of the chemotherapeutic agents presently used to treat solid tumors is limited by their low therapeutic index. Previously, our research group improved the in vitro antitumoral activity of gemcitabine, an anticancer agent rapidly deaminated to the inactive metabolite 2',2'-difluorodeoxyuridine, entrapping it into unilamellar pegylated liposomes made up of 1,2-dipalmitoyl-snglycero-3-phosphocholine monohydrate/cholesterol/N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (6:3:1 molar ratio). In this work, we investigated the in vivo efficiency of the gemcitabine liposomal formulation (5mg/kg) with respect to the antitumoral commercial product GEMZAR (50mg/kg) on an anaplastic thyroid carcinoma xenograft model obtaining similar effects in terms of inhibition of tumor mass proliferation after 4weeks of treatment. The investigation of the carrier biodistribution and the drug pharmacokinetic profile furnished the rationalization of the efficacy of the vesicular system containing the active compound 10-fold less concentrated; in fact, liposomes promoted the concentration of the drug inside the tumor and they increased its plasmatic half-life. In addition, no signs of blood toxicity were observed when vesicular devices of effective doses of the drug were used.
authors.affiliation: Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Campus Universitario S. Venuta - Building of BioSciences, Viale Europa, I-88100 Germaneto (CZ), Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Paolino
authors.forename: Donato
authors.initials: D
authors.lastname: Cosco
authors.forename: Leda
authors.initials: L
authors.lastname: Racanicchi
authors.forename: Elena
authors.initials: E
authors.lastname: Trapasso
authors.forename: Christian
authors.initials: C
authors.lastname: Celia
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Iannone
authors.forename: Efisio
authors.initials: E
authors.lastname: Puxeddu
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Costante
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.forename: Massimo
authors.initials: M
authors.lastname: Fresta
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D005467:Floxuridine / Q000031:analogs & derivatives; D006207:Half-Life; D008081:Liposomes / Q000493:pharmacokinetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011092:Polyethylene Glycols; D020849:Raloxifene Hydrochloride; D014018:Tissue Distribution; D053835:Unilamellar Liposomes; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D053835:Unilamellar Liposomes; D005467:Floxuridine; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D020849:Raloxifene Hydrochloride; C028210:monomethoxypolyethylene glycol; C084565:2',2'-difluoro-2'-deoxyuridine; D000093542:Gemcitabine