title: Liver targeting and the delayed drug release of the nanoparticles of adriamycin polybutylcyanoacrylate in mice.
abstract: BACKGROUND
  Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver.
  
  
  METHODS
  One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.
  
  
  RESULTS
  Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups (P < 0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of (22.3 +/- 6.2) nm (P < 0.05). The ADM-PBCA-NP in (101.0 +/- 20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of (143.0 +/- 23.5) nm diameter (P < 0.05). Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3 +/- 6.2) nm diameter was not distributed in the tissue of the liver, kidney, heart, spleen, and lung.
  
  
  CONCLUSIONS
  ADM-PBCA-NP in 100 - 150 nm diameter range has the best liver targeting with a characteristic of slow medicine release. It also decreases the medicine distribution in the heart, kidney and lung. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticles system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.
authors.affiliation: Department of Tumor, Xiangya Hospital, Central South University of China, Changsha 410008, China.
authors.forename: Liang-fang
authors.initials: LF
authors.lastname: Shen
authors.forename: Yang-de
authors.initials: YD
authors.lastname: Zhang
authors.forename: Hai-ju
authors.initials: HJ
authors.lastname: Shen
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Le
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004659:Enbucrilate / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D049329:Nanostructures; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D004659:Enbucrilate