Ibuprofen-loaded poly(trimethylene carbonate-co-ε-caprolactone) electrospun fibres for nerve regeneration.
The 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-ε-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 24 h. 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 E2 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.
INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Porto, Portugal.|Universidade do Porto, Faculdade de Engenharia, Porto, Portugal.
Liliana R
LR
Pires
Institute of Composite and Biomedical Materials, National Research Council, Naples, Italy.
Vincenzo
V
Guarino
INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Porto, Portugal.|Departamento de Patologia e Oncologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.
Maria J
MJ
Oliveira
INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Porto, Portugal.|ISEP - Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Porto, Portugal.
Cristina C
CC
Ribeiro
INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Porto, Portugal.|Universidade do Porto, Faculdade de Engenharia, Porto, Portugal.|Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal.
Mário A
MA
Barbosa
Institute of Composite and Biomedical Materials, National Research Council, Naples, Italy.
Luigi
L
Ambrosio
INEB - Instituto de Engenharia Biomédica, NEWTherapies Group, Universidade do Porto, Porto, Portugal.|Universidade do Porto, Faculdade de Engenharia, Porto, Portugal.|Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar, Porto, Portugal.
Ana Paula
AP
Pêgo
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004146:Dioxanes / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D009416:Nerve Regeneration / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D023822:Tissue Engineering / Q000379:methods*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004146:Dioxanes; D011091:Polyesters; C000612824:poly(trimethylene carbonate-co-epsilon-caprolactone); C443643:trimethylene carbonate; D015232:Dinoprostone; D007052:Ibuprofen
confocal Raman microscopy; drug delivery; electrospinning; ibuprofen; inflammation; nerve guide