Nano-engineered microcapsules boost the treatment of persistent pain |
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Authors: | Olga Kopach Kayiu Zheng Luo Dong Andrei Sapelkin Nana Voitenko |
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Affiliation: | 1. Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, London, UK;2. School of Engineering and Materials Science, Queen Mary University of London, London, UK;3. Centre for Condensed Matter and Materials Physics, Queen Mary University of London, London, UK;4. Department of Sensory Signaling, Bogomoletz Institute of Physiology, Kyiv, Ukraine |
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Abstract: | Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments. |
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Keywords: | Biodegradable microcapsules persistent pain Na+ channels drug diffusion neuronal excitability pain relief locomotive deficit and anxiety |
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