Ibuprofen-loaded fibrous patches-taming inhibition at the spinal cord injury site

Abstract

It is now widely accepted that a therapeutic strategy for spinal cord injury (SCI) demands a multi-target approach. Here we propose the use of an easily implantable bilayer polymeric patch based on poly(trimethylene carbonate-co-e-caprolactone) (P(TMC-CL)) that combines physical guidance cues provided by electrospun aligned fibres and the delivery of ibuprofen, as a mean to reduce the inhibitory environment at the lesion site by taming RhoA activation. Bilayer patches comprised a solvent cast film onto which electrospun aligned fibres have been deposited. Both layers were loaded with ibuprofen. In vitro release (37°C, in phosphate buffered saline) of the drug from the loaded scaffolds under sink condition was found to occur in the first 24 h. The released ibuprofen was shown to retain its bioactivity, as indicated by the reduction of RhoA activation when the neuronal-like cell line ND7/23 was challenged with lysophosphatidic acid. Ibuprofen-loaded P(TMC-CL) bilayer scaffolds were successfully implanted in vivo in a dorsal hemisection rat SCI model mediating the reduction of RhoA activation after 5 days of implantation in comparison to plain P(TMC-CL) scaffolds. Immunohistochemical analysis of the tissue shows ßIII tubulin positive cells close to the ibuprofen-loaded patches further supporting the use of this strategy in the context of regeneration after a lesion in the spinal cord.