title: Sustained delivery of growth factors from methylidene malonate 2.1.2-based polymers.
abstract: The incorporation of growth factors into new methylidene malonate 2.1.2-based biocompatible polymeric blends of oligomers and polymers to improve their stability and controlled release was investigated. Five growth factors were used in this study: FGF2, PDGF, TGF-beta, NGF and GM-CSF. Formulation in poly(methylidene malonate 2.1.2) blends was achieved by a four-step optimized process, using different oligomers/polymers ratios. Once dried, formulations could be subsequently stored at 4 or 20 degrees C or immediately subjected to degradation in conditioned cell culture medium. Toxicity of blends and their degradation products were evaluated in several cell lines with MTT. Bioactivity and biospecificity of the formulated growth factors were investigated using MTT and immunohistochemical staining. Combined ELISA and crystal violet colorimetric assays were performed to analyze growth factors release. Limited toxicities were observed for unloaded poly(methylidene malonate 2.1.2) blends. Once optimized, growth factors formulations did not reveal lower bioactivities or loss of biospecificity. Moreover, a sustained release over a 21-day period with more than 90% of preserved bioactivity was reached. To conclude, dual growth factor delivery was made possible by the mean of poly(methylidene malonate 2.1.2) blends. These studies demonstrate the ability of methylidene malonate 2.1.2-based polymeric blends for the delivery of growth factors.
authors.affiliation: UMR CNRS 8612, School of Pharmacy, University of Paris-Sud, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Désiré
authors.forename: Evgueni
authors.initials: E
authors.lastname: Mysiakine
authors.forename: David
authors.initials: D
authors.lastname: Bonnafous
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Serge
authors.initials: S
authors.lastname: Sagodira
authors.forename: Pascal
authors.initials: P
authors.lastname: Breton
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases; D006133:Growth Substances / Q000008:administration & dosage*; D008314:Malonates / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D011095:Polyethylenes / Q000737:chemistry*; D019736:Prostheses and Implants; D015398:Signal Transduction
chemical_list: D001672:Biocompatible Materials; D003470:Culture Media; D004337:Drug Carriers; D006133:Growth Substances; D008314:Malonates; D011095:Polyethylenes; C091414:poly(methylidene malonate) 2.1.2; D048049:Extracellular Signal-Regulated MAP Kinases