A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine.

Science Advances
Jiao FengPatrick Couvreur

Abstract

The clinical use of endogenous neuropeptides has historically been limited due to pharmacokinetic issues, including plasma stability and blood-brain barrier permeability. In this study, we show that the rapidly metabolized Leu-enkephalin (LENK) neuropeptide may become pharmacologically efficient owing to a simple conjugation with the lipid squalene (SQ). The corresponding LENK-SQ bioconjugates were synthesized using different chemical linkers in order to modulate the LENK release after their formulation into nanoparticles. This new SQ-based nanoformulation prevented rapid plasma degradation of LENK and conferred on the released neuropeptide a notable antihyperalgesic effect that lasted longer than after treatment with morphine in a rat model of inflammation (Hargreaves test). The biodistribution study as well as the use of brain-permeant and -impermeant opioid receptor antagonists indicated that LENK-SQ NPs act through peripherally located opioid receptors. This study represents a novel nanomedicine approach, allowing the specific delivery of LENK neuropeptide into inflamed tissues for pain control.

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Apr 19, 2020·Current Opinion in Supportive and Palliative Care·Christoph Stein
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Methods Mentioned

BETA
fluorescence imaging
nanoprecipitation
dynamic light scattering
transmission electron microscopy
column chromatography
electron microscopy

Software Mentioned

ImageJ
Living Image
Living Imaging
GraphPad Prism

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