title: [VCR-loaded nanoparticles as targeted delivery system for the treatment of orbital adenoid cystic carcinoma].
abstract: OBJECTIVE
  To prepare and observe the properties of Folate Receptor-mediated VCR-loaded nanoparticles, which is abbreviated as FA-PLGA (VCR)-NP and to study the inhibitory effect of FA-PLGA (VCR)-NP in ACC-2 cells in vitro and in ACC in BALB/c-nu mice.
  
  
  METHODS
  The mAified W/O/W extraction-evaporation technique was chosen to prepare FA-PLGA (VCR)-NP. Tumor cells were divided into three groups: VCR, PLGA (VCR)-NP and FA-PLGA (VCR)-NP. Seven doses (0.05, 0.25, 0.50, 1.00, 5.00, 10.00, and 30.00 mg/L) of VCR were tested in the cell culture mAel. After 1, 2, 3, 4 and 5 days, the cell growth inhibition ratio was evaluated by MTT colorimetry. Nude mice mAel of orbital ACC was built by injecting ACC cell suspension and divided into four groups: VCR, PLGA (VCR)-NP, FA-PLGA (VCR)-NP, and control group. After 1 day, 7 days and 14 days, the inhibition ratio of gross tumor volume was observed. Residual concentrations of VCR in tumors were evaluated by HPLC. The feature of histopathology was observed by electron microscopy. The effect of empty nanoparticles on ACC-2 cells was compared with normal control group using t-test to analyze. On account of different drugs, concentration, time and the interaction of them, multivariate analysis of variance was used to analyze their relationship. Inhibition rate and residual volume of drug concentrations were compared using one-factor analysis of variance and LSD method.
  
  
  RESULTS
  FA-PLGA (VCR)-NP were smooth and spherical with a mean particle size of 249.2 nm. The drug loading efficiency was 4.53%. The release of VCR from PLGA nanoparticles can persist for 14 d. After blank particles PLGA-NP and ACC-2 cells were co-cultured for 5 days, cell viability had remained at more than 80 percent (t = 1.952 ∼ 3.285, P = 0.081 ∼ 0.190). The inhibitory effect of FA-PLGA (VCR)-NP was more effective than VCR alone after a period of time (F = 4.798 ∼ 563.479, P = 0.000 ∼ 0.006). The effects of the treatment were both in dose-dependent and time-dependent manner. Targeting particles could attach to tumor surface, via folate receptor. FA was competitive inhibitor of this recolonization. The volume inhibition ratios of FA-PLGA (VCR)-NP and PLGA (VCR)-NP were significant higher than VCR (P = 0.016, P = 0.029). The inhibition ratio of FA-PLGA (VCR)-NP was higher than that of PLGA (VCR)-NP, but there was no statistical difference (P = 0.376). There was significant different between residual concentrations of VCR on the 1(st), 7(th) and 14(th) days. TEM pictures showed a mass of electron-dense microspheres in tumor cells on the 14(th) day. Tumor necrosis was obvious, while surrounding tissues were normal.
  
  
  CONCLUSIONS
  FA-PLGA (VCR)-NP are stable and have high drug entrapment efficiency and high effect of growth inhibition in vitro. It can be proposed as a potentially controlled and targeted delivery system for the treatment of ACC.
authors.affiliation: Tianjin Medical University Eye Center, Tianjin 300070, China. hyj222002@yahoo.com.cn
authors.forename: Yan-jin
authors.initials: YJ
authors.lastname: He
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Lin
authors.forename: Li-min
authors.initials: LM
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.forename: Jin
authors.initials: J
authors.lastname: Chang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Hong-mei
authors.initials: HM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D009918:Orbital Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000008:administration & dosage* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D014750:Vincristine; D005492:Folic Acid