Nano-engineered microcapsules boost the treatment of persistent pain. (1st January 2018)

• Record Type: Journal Article
• Authors: Kopach, Olga; Zheng, Kayiu; Dong, Luo; Sapelkin, Andrei; Voitenko, Nana; Sukhorukov, Gleb B.; Rusakov, Dmitri A.
• Is Part Of: Drug delivery. Volume 25:Number 1(2018)
• Page Start: 435
• Page End: 447
• Publication Date: 2018-01-01
• Subjects: Biodegradable microcapsules -- persistent pain -- Na+ channels -- drug diffusion -- neuronal excitability -- pain relief -- locomotive deficit and anxiety; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.1080/10717544.2018.1431981
• Languages: English
• ISSNs: 1071-7544

Abstract

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.