title: Bevacizumab-loaded polyurethane subconjunctival implants: effects on experimental glaucoma filtration surgery.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) may contribute to the scarring process resulting from glaucoma filtration surgery, since this cytokine may stimulate fibroblast proliferation. The aim of this study was to describe a new bevacizumab-loaded polyurethane implant (BPUI) and to evaluate its effectiveness as a new drug delivery system of anti-VEGF antibody in a rabbit model of glaucoma filtration surgery.
  
  
  METHODS
  An aqueous dispersion of polyurethane was obtained via the conventional process. Bevacizumab (1.5 mg) was then incorporated into the dispersion and was subsequently dried to form the polymeric films. Films with dimensions of 3×3×1 mm that either did (group BPUI, n=10) or did not contain bevacizumab (group PUI, n=10) were implanted in the subconjunctival space, at the surgical site in 1 eye of each rabbit. The in vitro bevacizumab release was evaluated using size-exclusion high-performance liquid chromatography (HPLC), and the in vivo effects of the drug were investigated in a rabbit experimental trabeculectomy model by examining the bleb characteristics and collagen accumulation, and by performing immunohistological analyses of VEGF expression.
  
  
  RESULTS
  HPLC showed that only 10% of the bevacizumab in the implants had been released by postoperative day 5. In vivo studies demonstrated that the drug had no adverse effects; however, no significant differences in either the bleb area score or the collagen deposit intensity between the group PUI and the group that BPUI were observed. Moreover, the group BPUI presented a significantly lower proportion of VEGF-expressing fibroblasts than group PUI (0.17±0.03 vs. 0.35±0.05 cells/field, P=0.005).
  
  
  CONCLUSIONS
  This study demonstrated that bevacizumab release from the BPUIs only occurred for a short time probably from the surface of the films. Nevertheless, they were well tolerated in rabbit eyes and reduced the number of VEGF-expressing fibroblasts.
authors: Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Ribeirão Preto-University of São Paulo, Ribeirão Preto, São Paulo, Brazil. jspaula@fmrp.usp.br
authors: Jayter Silva
authors: JS
authors: Paula
authors: Vanessa Raquel Coimbra
authors: VR
authors: Ribeiro
authors: Fernando
authors: F
authors: Chahud
authors: Roberta
authors: R
authors: Cannellini
authors: Tassia Cristina
authors: TC
authors: Monteiro
authors: Elionai Cassiana de Lima
authors: EC
authors: Gomes
authors: Peter Sol
authors: PS
authors: Reinach
authors: Maria de Lourdes Veronese
authors: Mde L
authors: Rodrigues
authors: Armando
authors: A
authors: Silva-Cunha
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000627:therapeutic use; D000068258:Bevacizumab; D002850:Chromatography, Gel; D002921:Cicatrix / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003228:Conjunctiva / Q000601:surgery; D004337:Drug Carriers / Q000737:chemistry*; D004343:Drug Implants; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018463:Filtering Surgery / Q000009:adverse effects; D005901:Glaucoma / Q000601:surgery*; D011140:Polyurethanes / Q000737:chemistry*; D011817:Rabbits; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004337:Drug Carriers; D004343:Drug Implants; D011140:Polyurethanes; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
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