title: A simple way to enhance Doxil® therapy: drug release from liposomes at the tumor site by amphiphilic block copolymer.
abstract: The antitumor efficacy of Doxil® is hindered by the poor release of the active drug from the liposome at the tumor sites. This study investigates a possibility to enhance drug release from the liposomes and increase therapeutic efficacy of Doxil® by administering Pluronic block copolymers once the liposomal drug accumulates in the tumor sites. In our study, the fluorescence de-quenching experiments were designed to investigate the drug release from liposome by Pluronic P85. MTT cytotoxicity assay and confocal microscopy images were carried out to determine whether Pluronic P85 could facilitate release of Dox from Doxil®. Anti-tumor growth and distribution of drug were evaluated when Pluronic P85 was injected 1h, 48h, or 96h after the Doxil® administration in A2780 human ovarian cancer xenografts. Addition of Pluronic P85 resulted in release of Dox from the liposomes accompanied with significant increases of Dox delivery and cytotoxic effect in cancer cells. The greatest anti-tumor effect of single injection of Doxil® was achieved when Pluronic P85 was administered 48h after Doxil®. The confocal tile scanning images of tumor section showed that copolymer treatment induced the release of the drug in the tumors from the vessels regions to the bulk of the tumor. No release of the drug remaining in circulation was observed. Our study has demonstrated a simple approach for localized release of Dox from liposome by Pluronic P85 at the tumor site, which was therapeutically beneficial.
authors.affiliation: Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198-5830, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Daria Y
authors.initials: DY
authors.lastname: Alakhova
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Bronich
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011060:Poloxalene / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; C422648:pluronic block copolymer p85; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011060:Poloxalene