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dc.creatorPires, L
dc.creatorGuarino, V
dc.creatorOliveira, M
dc.creatorRibeiro, C
dc.creatorBarbosa, M
dc.creatorAmbrosio, L
dc.creatorPêgo, AP
dc.description.abstractThe development of scaffolds that combine the delivery of drugs with the physical support provided by electrospun fibres holds great potential in the field of nerve regeneration. Here it is proposed the incorporation of ibuprofen, a well-known non-steroidal anti-inflammatory drug, in electrospun fibres of the statistical copolymer poly(trimethylene carbonate-co-e-caprolactone) [P(TMC-CL)] to serve as a drug delivery system to enhance axonal regeneration in the context of a spinal cord lesion, by limiting the inflammatory response. P(TMC-CL) fibres were electrospun from mixtures of dichloromethane (DCM) and dimethylformamide (DMF). The solvent mixture applied influenced fibre morphology, as well as mean fibre diameter, which decreased as the DMF content in solution increased. Ibuprofen-loaded fibres were prepared from P(TMC-CL) solutions containing 5% ibuprofen (w/w of polymer). Increasing drug content to 10% led to jet instability, resulting in the formation of a less homogeneous fibrous mesh. Under the optimized conditions, drug-loading efficiency was above 80%. Confocal Raman mapping showed no preferential distribution of ibuprofen in P(TMC-CL) fibres. Under physiological conditions ibuprofen was released in 24h. The release process being diffusion-dependent for fibres prepared from DCM solutions, in contrast to fibres prepared from DCM-DMF mixtures where burst release occurred. The biological activity of the drug released was demonstrated using human-derived macrophages. The release of prostaglandin E 2 to the cell culture medium was reduced when cells were incubated with ibuprofen-loaded P(TMC-CL) fibres, confirming the biological significance of the drug delivery strategy presented. Overall, this study constitutes an important contribution to the design of a P(TMC-CL)-based nerve conduit with anti-inflammatory properties.
dc.description.sponsorshipThis work was financed by FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia in the framework of the project PEst-C/SAU/LA0002/2011 and PTDC/CTM-NAN/115124/2009, PTDC/SAU-ONC/112511/2009. L.R.P. thanks FCT for her PhD grant (SFRH /BD / 46015 / 2008) and M.J.O. is a FCT Ciência 200 7 fello w. The authors acknowledge Centro de Materiais da Universidade do Por to (C EMUP; RE EQ/1062/C TM/20 05 from FCT ) for t he 1HNMR analysis.
dc.publisherJohn Wiley and Sons
dc.relation.ispartofJournal of Tissue Engineering and Regenerative Medicine, vol. 10(3), p. E154-E166
dc.subjectConfocal Raman microscopy
dc.subjectDrug delivery
dc.subjectNerve guide
dc.titleIbuprofen-loaded poly(trimethylene carbonate-co-e-caprolactone) electrospun fibres for nerve regeneration
dc.typeArtigo em Revista Científica Internacional
dc.contributor.uportoInstituto de Investigação e Inovação em Saúde
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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