Drug Delivery | |
Nano-engineered microcapsules boost the treatment of persistent pain | |
Andrei Sapelkin1  Dmitri A. Rusakov2  Kayiu Zheng2  Olga Kopach2  Nana Voitenko3  Luo Dong4  Gleb B. Sukhorukov4  | |
[1] Centre for Condensed Matter and Materials Physics, Queen Mary University of London, London, UK;Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, London, UK;Department of Sensory Signaling, Bogomoletz Institute of Physiology, Kyiv, Ukrain;School of Engineering and Materials Science, Queen Mary University of London, London, UK; | |
关键词: Biodegradable microcapsules; persistent pain; Na channels; drug diffusion; neuronal excitability; pain relief; locomotive deficit and anxiety; | |
DOI : 10.1080/10717544.2018.1431981 | |
来源: publisher | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
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RO202004239840284ZK.pdf | 3471KB | download |