title: Novel nanostructured lipid-dextran sulfate hybrid carriers overcome tumor multidrug resistance of mitoxantrone hydrochloride.
abstract: Novel nanostructured lipid-dextran sulfate hybrid carriers (NLDCs) were successfully developed for sustained delivery of water-soluble cationic mitoxantrone hydrochloride (MTO) and overcoming multidrug resistance. The introduction of negative polymer of dextran sulfate sodium significantly improved the encapsulation efficiency (97.4%) and sustained the release of MTO (86.9% at 72 hours). In vivo pharmacokinetics in rats after intravenous administration demonstrated that MTO-loaded NLDCs (MTO-NLDCs) had higher area under the curve and longer half-life than MTO solution (MTO-Sol). In the biodistribution study, NLDCs significantly improved the MTO levels in plasma, spleen, and brain, and decreased the distribution of MTO in heart and kidney. In comparison with MTO-Sol, MTO-NLDCs efficiently enhanced cytotoxicity through the higher accumulation of MTO in breast cancer resistance protein (BCRP)-overexpressing MCF-7/MX cells. MTO-NLDCs entered into the resistant cancer cells by the clathrin-mediated endocytosis pathway, which escaped the efflux induced by BCRP transporter and thereby overcame the multidrug resistance of MCF-7/MX cells.
  
  
  BACKGROUND
  In this study, novel nanostructured lipid-dextran sulfate hybrid carriers were synthesized and utilized for sustained delivery of mitoxantrone hydrochloride. The utilized methods successfully addressed multidrug resistance to this chemotherapy agent.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Guixia
authors.initials: G
authors.lastname: Ling
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Pan
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Pu
authors.forename: Shiliang
authors.initials: S
authors.lastname: Yin
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D016264:Dextran Sulfate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004705:Endocytosis; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008942:Mitoxantrone / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C489249:Abcg2 protein, rat; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D016264:Dextran Sulfate; D008942:Mitoxantrone