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Controlled local release of PPARγ agonists from biomaterials to treat peripheral nerve injury

Rayner, MLD; Grillo, A; Williams, G; Tawfik, E; Zhang, T; Volitaki, C; Craig, DQM; ... Phillips, J; + view all (2020) Controlled local release of PPARγ agonists from biomaterials to treat peripheral nerve injury. Journal of Neural Engineering 10.1088/1741-2552/aba7cc. (In press). Green open access

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Rayner+et+al_2020_J._Neural_Eng._10.1088_1741-2552_aba7cc.pdf - Accepted Version

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Abstract

Objective: Poor clinical outcomes following peripheral nerve injury (PNI) are partly attributable to the limited rate of neuronal regeneration. Despite numerous potential drug candidates demonstrating positive effects on nerve regeneration rate in preclinical models, no drugs are routinely used to improve restoration of function in clinical practice. A key challenge associated with clinical adoption of drug treatments in nerve injured patients is the requirement for sustained administration of doses associated with undesirable systemic side-effects. Local controlled-release drug delivery systems could potentially address this challenge, particularly through the use of biomaterials that can be implanted at the repair site during the microsurgical repair procedure. Approach: In order to test this concept, this study used various biomaterials to deliver ibuprofen sodium or sulindac sulfide locally in a controlled manner in a rat sciatic nerve injury model. Following characterisation of release parameters in vitro, ethylene vinyl acetate (EVA) tubes or polylactic-co-glycolic acid (PLGA) wraps, loaded with ibuprofen sodium or sulindac sulfide, were placed around directly-repaired nerve transection or nerve crush injuries in rats. Main results: Ibuprofen sodium, but not sulindac sulfide caused an increase in neurites in distal nerve segments and improvements in functional recovery in comparison to controls with no drug treatment. Significance: This study showed for the first time that local delivery of ibuprofen sodium using biomaterials improves neurite growth and functional recovery following PNI and provides the basis for future development of drug-loaded biomaterials suitable for clinical translation.

Type: Article
Title: Controlled local release of PPARγ agonists from biomaterials to treat peripheral nerve injury
Open access status: An open access version is available from UCL Discovery
DOI: 10.1088/1741-2552/aba7cc
Publisher version: http://dx.doi.org/10.1088/1741-2552/aba7cc
Language: English
Additional information: As the Version of Record of this article is going to be/has been published on a gold open access basis under a CC BY 3.0 licence, this Accepted Manuscript is available for reuse under a CC BY 3.0 licence immediately. Although reasonable endeavours have been taken to obtain all necessary permissions from third parties to include their copyrighted content within this article, their full citation and copyright line may not be present in this Accepted Manuscript version. Before using any content from this article, please refer to the Version of Record on IOPscience once published for full citation and copyright details, as permission may be required. All third party content is fully copyright protected, and is not published on a gold open access basis under a CC BY licence, unless that is specifically stated in the figure caption in the Version of Record.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases > UCL Institute of Prion Diseases Support
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10106610
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