title: In vivo release and retinal safety of intravitreal implants of thalidomide in rabbit eyes and antiangiogenic effect on the chorioallantoic membrane.
abstract: OBJECTIVE
  To evaluate the in vivo release, retinal safety and antiangiogenic effect of a thalidomide-loaded poly-lactide-co-glycolide intravitreal implant.
  
  
  METHODS
  New Zealand white rabbits, divided into two groups, I and II, received an intravitreal implant containing or not thalidomide, respectively (n = 12). Intravitreal drug levels were determined during a six-week study period. The potential for toxicity associated with the implants was evaluated by electroretinography and light microscopy (n = 8). Twelve chorioallantoic membranes (CAMs) from chicken eggs were incubated with thalidomide dispersion, implants containing or not thalidomide and vitreous samples and analyzed after two days regarding the percentage of vessels regression.
  
  
  RESULTS
  Intravitreal concentrations of thalidomide (ng/ml) were 690.21 ± 177.95, 372.51 ± 185.56, 240.59 ± 133.48, 327.54 ± 169.71, 294.26 ± 142.41 and 465.18 ± 157.51 at 1, 2, 3, 4, 5 and 6 weeks, respectively, after implantation in group I rabbits. No drug was detected in group II samples. Electroretinography and histological evaluations did not show any sign of retina toxicity. There was significant regression of vessels in CAM incubated with thalidomide dispersion, thalidomide-loaded implants and vitreous samples from group I when compared to control.
  
  
  CONCLUSIONS
  The intravitreal implants delivered safe doses of thalidomide that were also effective to induce vessels regression in CAMs.
authors: Pharmaceutical and Biotechnological Development, Ezequiel Dias Foundation , Belo Horizonte , Brazil .
authors: Silvia L
authors: SL
authors: Fialho
authors: Pedro A F
authors: PA
authors: Souza
authors: Gustavo O
authors: GO
authors: Fulgêncio
authors: Murilo M O
authors: MM
authors: Miranda
authors: Bruno G
authors: BG
authors: Pereira
authors: Antonio
authors: A
authors: Haddad
authors: André
authors: A
authors: Messias
authors: Rodrigo
authors: R
authors: Jorge
authors: Armando
authors: A
authors: Silva-Cunha
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects*; D004343:Drug Implants; D004596:Electroretinography; D005260:Female; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012995:Solubility; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D004343:Drug Implants; D013792:Thalidomide