title: Antiangiogenic activity of a bevacizumab-loaded polyurethane device in animal neovascularization models.
abstract: OBJECTIVE
  To evaluate the antiangiogenic activity of bevacizumab-loaded polyurethane using two animal models of neovascularization.
  
  
  METHODS
  The percentage of blood vessels was evaluated in a chicken chorioallantoic membrane model (n=42) and in the rabbit cornea (n=24) with neovascularization induced by alkali injury. In each model, the animals were randomly divided into the groups treated with the bevacizumab-loaded polyurethane device, phosphate-buffered-saline (negative control) and bevacizumab commercial solution (positive control). Clinical examination, as well as histopathological and immunohistochemical evaluation, were performed in the rabbit eyes. Microvascular density in hot spot areas was determined in semi-thin sections of corneal tissue by hematoxylin-eosin staining and factor VIII immunohistochemistry. Immunohistochemical analysis was also performed to evaluate VEGF expression.
  
  
  RESULTS
  In the evaluated models, the use of bevacizumab (Avastin®) and the bevacizumab-loaded polyurethane device led to similar results with regard to inhibition of neovascularization. In the chorioallantoic membrane model, the bevacizumab-loaded polyurethane device reduced angiogenesis by 50.27% when compared to the negative control group. In the rabbit model of corneal neovascularization, the mean density of vessels/field was reduced by 46.87% on analysis of factor VIII immunohistochemistry photos in the bevacizumab-loaded polyurethane device group as compared to the negative control (PBS) sections. In both models, no significant difference could be identified between the bevacizumab-loaded polyurethane device and the positive control group, leading to similar results with regard to inhibition of neovascularization.
  
  
  CONCLUSIONS
  The present study shows that the bevacizumab-loaded polyurethane device may release bevacizumab and inhibit neovascularization similarly to commercial bevacizumab solution in the short-term.
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil; Pharmaceutical Research and Development, Ezequiel Dias Foundation, Rua Conde Pereira Carneiro, 80 - Gameleira, CEP 30510-010, Belo Horizonte, MG, Brazil.
authors.forename: A E R
authors.initials: AE
authors.lastname: Ferreira
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: B F M
authors.initials: BF
authors.lastname: Castro
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: L C
authors.initials: LC
authors.lastname: Vieira
authors.affiliation: Department of General Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: G D
authors.initials: GD
authors.lastname: Cassali
authors.affiliation: Department of General Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: C M
authors.initials: CM
authors.lastname: Souza
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: G O
authors.initials: GO
authors.lastname: Fulgêncio
authors.affiliation: Department of Materials, Technologies and Processes, Minas Gerais State University, Belo Horizonte, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Ayres
authors.affiliation: Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: R L
authors.initials: RL
authors.lastname: Oréfice
authors.affiliation: Department of Ophthalmology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Jorge
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Silva-Cunha
authors.affiliation: Pharmaceutical Research and Development, Ezequiel Dias Foundation, Rua Conde Pereira Carneiro, 80 - Gameleira, CEP 30510-010, Belo Horizonte, MG, Brazil. Electronic address: silvia.fialho@funed.mg.gov.br.
authors.forename: S L
authors.initials: SL
authors.lastname: Fialho
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage*; D002642:Chick Embryo; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D004343:Drug Implants / Q000737:chemistry; D005260:Female; D011140:Polyurethanes / Q000737:chemistry; D011817:Rabbits
chemical_list: D020533:Angiogenesis Inhibitors; D004337:Drug Carriers; D004343:Drug Implants; D011140:Polyurethanes; D000068258:Bevacizumab
keywords: Angiogenesis inhibitors; Corneal neovascularization; Drug vehicles; Inhibiteurs de l’angiogenèse; Neovascularization; Néovascularisation; Néovascularisation cornéenne; Polymers; Polymère; Vecteurs de médicaments