title: Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay.
abstract: BACKGROUND
  Doxorubicin (DOX)-loaded folate-targeted poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) [P(HB-HO)] nanoparticles [DOX/FA-PEG-P(HB-HO) NPs] were prepared by the W1/O/W2 solvent extraction/evaporation method for applications in cancer treatment. However, the biodistribution, pharmacokinetics, and targeting of the nanoparticles (NPs) have not yet been studied.
  
  
  OBJECTIVE
  The biodistribution, pharmacokinetics, and targeting of DOX/FA-PEG-P(HB-HO) NPs were evaluated in female BALB/c nude mice bearing HeLa tumors.
  
  
  METHODS
  Three DOX formulations were injected into the tail vein of the mice at a dosage of 5 mg/kg. At each time point, blood and various tissues were collected. All samples were then processed and analyzed by a validated high performance liquid chromatographic (HPLC) method.
  
  
  RESULTS
  The t1/2 values of DOX/P(HB-HO) NPs and DOX/FA-PEG-P(HB-HO) NPs were 2.7- and 3.5-times higher than that of free DOX. No significant difference (p > 0.05) was found in Cmax between the NPs and free DOX. The Tmax values of the two NPs were prolonged from 0.25 to 1 h. The AUC0-t values were 1.55- and 3.05-folds higher than that of free DOX, and MRT increased to 15.99 h for DOX/P(HB-HO) NPs and 25.14 h for DOX/FA-PEG-P(HB-HO) NPs. For DOX/FA-PEG-P(HB-HO) NPs, the DOX content in the tumors were 10.81- and 3.33-times higher than those for free DOX and DOX/P(HB-HO) NPs at 48 h, respectively.
  
  
  CONCLUSIONS
  DOX/FA-PEG-P(HB-HO) NPs displayed reduced cardiac toxicity and improved bioavailability. Moreover, the NPs exhibited a significant extent of DOX accumulation in the tumors, thus suggesting that folate-targeted NPs could effectively transport into HeLa tumors with satisfying targeting.
authors.affiliation: a School of Environment and Safety, Taiyuan University of Science and Technology , Taiyuan , China .
authors.forename: Chan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: b College of Life Science, Shanxi University , Taiyuan , China , and.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: c Shanxi Institute of Medicine and Life Science , Taiyuan , China.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Dong
authors.affiliation: a School of Environment and Safety, Taiyuan University of Science and Technology , Taiyuan , China .
authors.forename: Hongying
authors.initials: H
authors.lastname: Xu
authors.affiliation: b College of Life Science, Shanxi University , Taiyuan , China , and.
authors.forename: Liangqi
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D019540:Area Under Curve; D001682:Biological Availability; D066126:Cardiotoxicity; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D004337:Drug Carriers; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D006207:Half-Life; D006367:HeLa Cells; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D018570:Risk Assessment; D014018:Tissue Distribution; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000094122:Polyhydroxybutyrates
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D004337:Drug Carriers; D005492:Folic Acid; D011091:Polyesters; C476611:poly(3-hydroxybutyrate-co-3-hydroxyoctanoate); D000094122:Polyhydroxybutyrates
keywords: Biodistribution; folate-targeted nanoparticles; high performance liquid chromatographic method; pharmacokinetics; poly(3-hydroxybutyrate-co-3-hydroxyoctanoate)