title: Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer.
abstract: BACKGROUND
  Polymeric micelles using amphiphilic macromolecules are promising vehicles for antitumor targeting. In this study, we prepared anticancer agent-incorporated polymeric micelles using novel block copolymer.
  
  
  METHODS
  We synthesized a block copolymer composed of dextran and poly (DL-lactide-co-glycolide) (DexbLG) for antitumor drug delivery. Doxorubicin was selected as the anticancer drug, and was incorporated into polymeric micelles by dialysis. Polymeric micelles were observed by transmission electron microscopy to be spherical and smaller than 100 nm, with a narrow size distribution. The particle size of doxorubicin-incorporated polymeric micelles increased with increasing drug content. Higher initial drug feeding also increased the drug content.
  
  
  RESULTS
  During the drug-release study, an initial burst release of doxorubicin was observed for 10 hours, and doxorubicin was continuously released over 4 days. To investigate the in vitro anticancer effects of the polymeric micelles, doxorubicin-resistant HuCC-T1 cells were treated with a very high concentration of doxorubicin. In an antiproliferation study, the polymeric micelles showed higher cytotoxicity to doxorubicin-resistant HuCC-T1 cells than free doxorubicin, indicating that the polymeric micelles were effectively engulfed by tumor cells, while free doxorubicin hardly penetrated the tumor cell membrane. On confocal laser scanning microscopy, free doxorubicin expressed very weak fluorescence intensity, while the polymeric micelles expressed strong red fluorescence. Furthermore, in flow cytometric analysis, fluorescence intensity of polymeric micelles was almost twice as high than with free doxorubicin.
  
  
  CONCLUSIONS
  DexbLG polymeric micelles incorporating doxorubicin are promising vehicles for antitumor drug targeting.
authors.affiliation: National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Do Hyung
authors.initials: DH
authors.lastname: Kim
authors.forename: Chung-Wook
authors.initials: CW
authors.lastname: Chung
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Yoo
authors.forename: Kyung Ha
authors.initials: KH
authors.lastname: Choi
authors.forename: Cy Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Ha
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D003956:Dialysis; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008823:Micelles; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D019906:Nuclear Magnetic Resonance, Biomolecular; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018709:Statistics, Nonparametric
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D003911:Dextrans; D008823:Micelles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin