title: Efficacy of methotrexate-loaded poly(ε-caprolactone) implants in Ehrlich solid tumor-bearing mice.
abstract: BACKGROUND
  Methotrexate (MTX) is used in the treatment of malignancies; however, its clinical application is limited by its toxic dose-related side effects. An alternative to overcome the toxicity of the MTX in healthy tissues is the design of an implantable device capable of controlling the delivery of this drug for an extended period within the tumor site.
  
  
  OBJECTIVE
  To develop methotrexate-loaded poly(ε-caprolactone) implants (MTX PCL implants) and to demonstrate their efficacy as local drug delivery systems capable of inhibiting Ehrlich solid tumor bearing mice.
  
  
  METHODS
  MTX PCL implants were produced by the melt-molding technique and were characterized by FTIR, WAXS, DSC and SEM. The in vitro and in vivo release of MTX from the PCL implants was also evaluated. The efficacy of implants in inhibiting tumor cells in culture and the solid tumor in a murine model was revealed.
  
  
  CONCLUSIONS
  The chemical and morphological integrity of the drug was preserved into the polymeric matrix. The in vitro and in vivo release processes of the MTX from the PCL implants were modulated by diffusion. MTX diffused from the implants revealed an antiproliferative effect on tumor cells. Finally, MTX controlled and sustained released from the polymeric implants efficiently reduced 42.7% of the solid tumor in mice paw.
  
  
  CONCLUSIONS
  These implantable devices represented a contribution to improve the efficacy and safety of chemotherapy treatments, promoting long-term local drug accumulation in the targeted site.
authors.affiliation: School of Pharmacy, Federal University of São João Del Rei, Divinópolis, Minas Gerais, Brazil.
authors.forename: Adriana De Fátima
authors.initials: Ade F
authors.lastname: Pereira
authors.forename: Leticia Gonçalves Resende
authors.initials: LG
authors.lastname: Pereira
authors.forename: Leandro Augusto De Oliveira
authors.initials: LA
authors.lastname: Barbosa
authors.forename: Sílvia Ligório
authors.initials: SL
authors.lastname: Fialho
authors.forename: Bruno Gonçalves
authors.initials: BG
authors.lastname: Pereira
authors.forename: Patrícia Santiago De Oliveira
authors.initials: PS
authors.lastname: Patricio
authors.forename: Flávia Carmo Horta
authors.initials: FC
authors.lastname: Pinto
authors.forename: Gisele Rodrigues
authors.initials: GR
authors.lastname: Da Silva
mesh_terms: D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D004343:Drug Implants; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome; D014961:X-Ray Diffraction
chemical_list: D004343:Drug Implants; D011091:Polyesters; C016240:polycaprolactone; D008727:Methotrexate