Drug Therapies for Peripheral Nerve Injuries

Rayner, Melissa; Healy, Jess; Phillips, James B.

doi:10.1007/978-3-030-06217-0_16-1

Cited by 2 publications

(4 citation statements)

References 152 publications

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“…These data (and others) collectively demonstrate the potential for local delivery of therapeutics to improve regeneration following a PNI (Daeschler et al, 2021 ; Rayner, Healy, & Phillips, 2020 ; Tajdaran et al, 2015 , 2019 ; Zuo et al, 2020 ). However, there remain outstanding issues and limited data on exactly how much drug reaches the target or how to optimize dosing strategies in vivo.…”

Section: Local Drug Deliverymentioning

confidence: 73%

“…Controlled release of ibuprofen and sulindac sulphide (both peroxisome proliferator‐activated receptor gamma agonists) has been tested using of various drug‐loaded polymers. In these studies, increased axon counts were detected in the distal stump of injured rat nerves following local delivery of ibuprofen from ethylene vinyl acetate (EVA) tubes and electrospun PLGA/ibuprofen or sulindac sulfide nanofibers formed into a nerve wrap (Rayner, Healy, & Phillips, 2020 ).…”

Section: Local Drug Deliverymentioning

confidence: 99%

“…A number of drugs have, however, shown promise preclinically for improving regeneration after peripheral nerve injury (PNI) including small molecules, immunosuppressants, and growth factors (Bota & Fodor, 2019 ; Rayner, Healy, & Phillips, 2020 ). These drugs are typically delivered systemically; translation to the clinic has been hindered by the challenge of achieving an effective concentration at the injured nerve, without causing adverse effects to other tissues and organs.…”

Section: Introductionmentioning

confidence: 99%

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Perspectives on optimizing local delivery of drugs to peripheral nerves using mathematical models

Laranjeira

Roberton

Phillips

et al. 2023

WIREs Mechanisms of Disease

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Drug therapies for treating peripheral nerve injury repair have shown significant promise in preclinical studies. Despite this, drug treatments are not used routinely clinically to treat patients with peripheral nerve injuries. Drugs delivered systemically are often associated with adverse effects to other tissues and organs; it remains challenging to predict the effective concentration needed at an injured nerve and the appropriate delivery strategy. Local drug delivery approaches are being developed to mitigate this, for example via injections or biomaterialmediated release. We propose the integration of mathematical modeling into the development of local drug delivery protocols for peripheral nerve injury repair. Mathematical models have the potential to inform understanding of the different transport mechanisms at play, as well as quantitative predictions around the efficacy of individual local delivery protocols. We discuss existing approaches in the literature, including drawing from other research fields, and present a process for taking forward an integrated mathematical-experimental approach to accelerate local drug delivery approaches for peripheral nerve injury repair.

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Section: Local Drug Deliverymentioning

confidence: 73%

Section: Local Drug Deliverymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Perspectives on optimizing local delivery of drugs to peripheral nerves using mathematical models

Laranjeira

Roberton

Phillips

et al. 2023

WIREs Mechanisms of Disease

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“…The immunosuppressive mechanism of action is the inhibition of T-cell activation, via inhibition of calcineurin signalling and interleukin-2 synthesis, leading to failure of T-cell proliferation and maturation 7,8 . Tacrolimus is also well established as an enhancer of nerve regeneration and A c c e p t e d M a n u s c r i p t therefore has been used to improve nerve repair, where doses lower than those required for immunosuppression can have a beneficial effect (reviewed comprehensively in [9][10][11] ). The proregenerative effects of tacrolimus are thought to be mediated via reduced scarring and activation of the ERK pathway in neural cells 12 .…”

Section: Introductionmentioning

confidence: 99%

Local delivery of tacrolimus using electrospun poly-ϵ-caprolactone nanofibres suppresses the T-cell response to peripheral nerve allografts

et al. 2023

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Objective: Repair of nerve gap injuries can be achieved through nerve autografting, but this approach is restricted by limited tissue supply and donor site morbidity. The use of living nerve allografts would provide an abundant tissue source, improving outcomes following peripheral nerve injury. Currently this approach is not used due to the requirement for systemic immunosuppression, to prevent donor-derived cells within the transplanted nerve causing an immune response, which is associated with severe adverse effects. The aim of this study was to develop a method for delivering immunosuppression locally, then to test its effectiveness in reducing the immune response to transplanted tissue in a rat model of nerve allograft repair. Approach: A coaxial electrospinning approach was used to produce poly-ε-caprolactone fibre sheets loaded with the immunosuppressant tacrolimus. The material was characterised in terms of structure and tacrolimus release, then tested in vivo through implantation in a rat sciatic nerve allograft model with immunologically mismatched host and donor tissue. Main results: Following successful drug encapsulation, the fibre sheets showed nanofibrous structure and controlled release of tacrolimus over several weeks. Materials containing tacrolimus (and blank material controls) were implanted around the nerve graft at the time of allograft or autograft repair. The fibre sheets were well tolerated by the animals and tacrolimus release resulted in a significant reduction in lymphocyte infiltration at three weeks post-transplantation. Significance: These findings demonstrate proof of concept for a novel nanofibrous biomaterial-based targeted drug delivery strategy for immunosuppression in peripheral nerve allografting.

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Drug Therapies for Peripheral Nerve Injuries

Cited by 2 publications

References 152 publications

Perspectives on optimizing local delivery of drugs to peripheral nerves using mathematical models

Perspectives on optimizing local delivery of drugs to peripheral nerves using mathematical models

Local delivery of tacrolimus using electrospun poly-ϵ-caprolactone nanofibres suppresses the T-cell response to peripheral nerve allografts

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