title: Albumin nanoparticles increase the anticancer efficacy of albendazole in ovarian cancer xenograft model.
abstract: BACKGROUND
  The poor prognosis of patients with drug resistant ovarian cancer and the lack of targeted therapy have raised the need for alternative treatments. Albendazole (ABZ) is an anti-parasite compound capable of impairing microtubule formation. We hypothesized that ABZ could be repurposed as a potential anti-angiogenic drug due to its potent inhibition of vascular endothelial growth factor (VEGF) in ovarian cancer with ascites. However, the poor aqueous solubility of ABZ limits its potential for cancer therapy. In this study, we have assembled ABZ with bovine serum albumin into nanoparticles with a size range of 7-10 nm (BSA-ABZ) and 200-250 nm (Nab-ABZ). We further examined the anticancer effects of ABZ carrying nanoparticles in ovarian cancer cells, in both in vitro and in vivo models.
  
  
  RESULTS
  Drug release studies demonstrated that about 93% of ABZ was released from BSA-ABZ 10 nm in comparison to 83% from Nab-ABZ 200 nm at pH 7.4 in 8 days. In vitro cell proliferation studies showed that the BSA-ABZ 10 nm exhibited the highest killing efficacy of ovarian cancer cells with surprisingly least toxicity to healthy ovarian epithelial cells. Confocal microscopy and fluorescence activated cell sorting analysis (FACS) revealed more efficient internalization of the BSA-ABZ 10 nm by cancer cells. For in vivo studies, we examined the tumor growth, ascites formation and the expression of VEGF and secreted protein acidic and rich in cysteine (SPARC) in tumor samples and only VEGF in plasma samples. The BSA-ABZ 10 nm reduced the tumor burden significantly (p < 0.02) at a much lower drug dose (10 μg/ml) compare to free drug. Both formulations were capable of suppressing the ascites volume significantly (p < 0.05) and reducing the number of ascites cells. The expression of VEGF and SPARC was also reduced, which indicates the underlying therapeutic mechanism of the ABZ.
  
  
  CONCLUSIONS
  Our data suggest that the BSA-ABZ may hold promise for the treatment and control of progression of ovarian cancer with ascites. However further studies are required to examine the efficacy of both the formulations in aggressive models of recurrent ovarian cancer with respect to particle size and dosing parameters.
authors.affiliation: Centre for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales, Sydney, NSW, Australia. lubna.noorani@unsw.edu.au.|Department of Surgery, St. George Clinical School, Faculty of Medicine, University of New South Wales, Kogarah, NSW, Australia. lubna.noorani@unsw.edu.au.
authors.forename: Lubna
authors.initials: L
authors.lastname: Noorani
authors.affiliation: Centre for Advanced Macromolecular Design (CAMD), School of Chemistry, University of New South Wales, Sydney, NSW, Australia. m.stenzel@unsw.edu.au.
authors.forename: Martina
authors.initials: M
authors.lastname: Stenzel
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia. Roger.Liang@newcastle.edu.au.
authors.forename: Roger
authors.initials: R
authors.lastname: Liang
authors.affiliation: Department of Surgery, St. George Clinical School, Faculty of Medicine, University of New South Wales, Kogarah, NSW, Australia. mhpourgholami@hotmail.com.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Pourgholami
authors.affiliation: Department of Surgery, St. George Clinical School, Faculty of Medicine, University of New South Wales, Kogarah, NSW, Australia. David.Morris@unsw.edu.au.
authors.forename: David L
authors.initials: DL
authors.lastname: Morris
mesh_terms: D015766:Albendazole / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001202:Ascitic Fluid / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D015676:Osteonectin / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010053:Ovary / Q000166:cytology; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015676:Osteonectin; C577241:SPARC protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D012710:Serum Albumin, Bovine; D015766:Albendazole