title: In vitro/in vivo comparison of drug release and polymer erosion from biodegradable P(FAD-SA) polyanhydrides--a noninvasive approach by the combined use of electron paramagnetic resonance spectroscopy and nuclear magnetic resonance imaging.
abstract: OBJECTIVE
  The purpose of this study was to compare drug release and polymer erosion from biodegradable P(FAD-SA) polyanhydrides in vitro and in vivo in real time and with minimal disturbance of the investigated system.
  
  
  METHODS
  P(FAD-SA) 20:80 and P(FAD-SA) 50:50 polymer tablets were loaded with the spin probe 3-carboxy-2,2,5,5-tetramethyl-pyrrollidine-1-oxyl (PCA) and implanted subcutaneously in the neck of rats or placed in 0.1 M phosphate buffer. 1.1 GHz EPR spectroscopy experiments and 7T MRI studies (T1 and T2 weighted) were performed.
  
  
  RESULTS
  A front of water penetration was visible by MRI in vitro in the case of P(FAD-SA) 20:80, but not for P(FAD-SA) 50:50. For both polymers, the thickness of the tablets decreased with time and a insoluble, easy deformable residue remained. Important processes such as edema, deformation of the implant, encapsulation and bioresorption were observable by MRI in vivo. P(FAD-SA) 50:50 was almost entirely absorbed by day 44, whereas an encapsulated residue was found for P(FAD-SA) 20:80 after 65 days. The EPR studies gave direct evidence of a water penetration induced changes of the microenvironment inside the tablet. EPR signals were still detectable in P(FAD-SA) 20:80 implants after 65 days, while the nitroxide was released in vitro within 16 days.
  
  
  CONCLUSIONS
  Important parameters and processes such as edema, deformation of the tablet, microviscosity inside the tablet and encapsulation can be monitored in real time by the combined use of the noninvasive techniques MRI and EPR leading to better understanding of the differences between the in vitro and in vivo situation.
authors.affiliation: Institute of Pharmacy Humboldt-University Berlin, Germany. Karsten = Maeder@rz.hu-berlin.de
authors.forename: K
authors.initials: K
authors.lastname: Mäder
authors.forename: Y
authors.initials: Y
authors.lastname: Crémmilleux
authors.forename: A J
authors.initials: AJ
authors.lastname: Domb
authors.forename: J F
authors.initials: JF
authors.lastname: Dunn
authors.forename: H M
authors.initials: HM
authors.lastname: Swartz
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry; D003652:Decanoic Acids / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D008279:Magnetic Resonance Imaging; D008297:Male; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D013229:Stearic Acids / Q000737:chemistry*; D013607:Tablets
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D003497:Cyclic N-Oxides; D003652:Decanoic Acids; D011108:Polymers; D013113:Spin Labels; D013229:Stearic Acids; D013607:Tablets; C090873:stearic-sebacic acid polyanhydride copolymer; C032289:2,2,5,5-tetramethyl-1-pyrrolidinyloxy-3-carboxylic acid