title: Development of thalidomide-loaded biodegradable devices and evaluation of the effect on inhibition of inflammation and angiogenesis after subcutaneous application.
abstract: OBJECTIVE
  To develop thalidomide-loaded poly-lactide-co-glycolide implants and evaluate its in vivo release and biological activity against inflammation and angiogenesis after subcutaneous administration.
  
  
  METHODS
  Implants were prepared by the hot molding technique and characterized using stereomicroscopy, thermal analysis and X-ray diffraction. Swiss mice, divided in groups 1-3, received a subcutaneous implant containing 25% (w/w), 50% (w/w) or 75% (w/w) of thalidomide, respectively (n=6). The drug levels were determined during a 28-day study period. The toxicity associated with the implants was evaluated by light microscopy. The potential of the developed implant in the inhibition of inflammation and angiogenesis was evaluated in vivo using the sponge model.
  
  
  RESULTS
  Thalidomide implant was developed and its characterization proved the stability of the drug and the polymer during preparation. Release profiles in vivo demonstrated an extended release of thalidomide from the implants during the 28 days. Histological evaluation did not show any sign of intense local inflammatory response to the presence of the implants in the subcutaneous pouch. The thalidomide implant reduced the number of vessels and N-acetyl-b-glucosaminidase (NAG) in vivo.
  
  
  CONCLUSIONS
  The biodegradable implants delivered safe doses of thalidomide that were also effective to induce angiogenesis and inflammation regression.
authors.affiliation: Pharmaceutical Research and Development, Ezequiel Dias Foundation - Funed, Belo Horizonte, Brazil; Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Bruno Gonçalves
authors.initials: BG
authors.lastname: Pereira
authors.affiliation: Pharmaceutical Research and Development, Ezequiel Dias Foundation - Funed, Belo Horizonte, Brazil.
authors.forename: Leandro Flores
authors.initials: LF
authors.lastname: Batista
authors.affiliation: Pharmaceutical Research and Development, Ezequiel Dias Foundation - Funed, Belo Horizonte, Brazil.
authors.forename: Pedro Alcântara Fonseca
authors.initials: PA
authors.lastname: de Souza
authors.affiliation: Faculty of Pharmacy, Federal University of São João Del Rei, Divinópolis, Brazil.
authors.forename: Gisele Rodrigues
authors.initials: GR
authors.lastname: da Silva
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Silvia Passos
authors.initials: SP
authors.lastname: Andrade
authors.affiliation: School of Veterinary, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Rogéria
authors.initials: R
authors.lastname: Serakides
authors.affiliation: Department of Chemistry, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Wagner
authors.initials: W
authors.lastname: da Nova Mussel
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Armando
authors.initials: A
authors.lastname: Silva-Cunha
authors.affiliation: Pharmaceutical Research and Development, Ezequiel Dias Foundation - Funed, Belo Horizonte, Brazil. Electronic address: silvia.fialho@funed.mg.gov.br.
authors.forename: Sílvia Ligório
authors.initials: SL
authors.lastname: Fialho
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004195:Disease Models, Animal; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013792:Thalidomide / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D006454:Hemoglobins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013792:Thalidomide; D009195:Peroxidase; D000118:Acetylglucosaminidase
keywords: Anti-angiogenic; Anti-inflammatory; Delivery system; PLGA; Sponge model