title: Stability influences the biodistribution, toxicity, and anti-tumor activity of doxorubicin encapsulated in PEG-PE micelles in mice.
abstract: OBJECTIVE
  To investigate the influences of stability of doxorubicin (DOX) retained in PEG-PE/HSPC micelles on its biodistribution, toxicity and anti-tumor activity in mice.
  
  
  METHODS
  We incorporated HSPC into PEG-PE micelles at various molar ratios by a self-assembly procedure. Micelles were characterized by dynamic light scattering, transmission electron microscope, atomic force microscopy. Agarose gel electrophoresis assay was used to detect stable retention of DOX in micellar preparations. Biodistribution, toxicity and anti-tumor activity of doxorubicin encapsulated in PEG-PE/HSPC micelles in mice were investigated.
  
  
  RESULTS
  HSPC incorporation not only changed the size and shape of PEG-PE micelles, but also decreased the ability of DOX stable retained in PEG-PE micelles, resulting in a great discrepancy in biodistribution, toxicity and anti-tumor activity among micellar DOX preparations. DOX encapsulated in PEG-PE micelles (M₁-DOX), with narrower size distribution and greater stability, demonstrated better cytotoxicity in vitro and low systemic toxicity with superior anti-tumor metastasis activity in vivo.
  
  
  CONCLUSIONS
  Encapsulation of DOX into PEG-PE micelles showed the best therapeutic activity and lowest systemic toxicity compared to other HSPC-incorporated PEG-PE micellar preparations. Stable retention of drugs within micelles is important and is determined by compatibility between drugs and polymer blocks.
authors.affiliation: Protein & Peptide Pharmaceutical Laboratory National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wei
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Zeng
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D010714:Phosphatidylethanolamines; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin