title: Mesoporous Silica Particles as a Multifunctional Delivery System for Pain Relief in Experimental Neuropathy.
abstract: The long-term use of potent analgesics is often needed to treat chronic pain. However, it has been greatly hindered by their side effects such as addiction and withdrawal reactions. The study seeks to circumvent these drawbacks by taking advantage of a multifunctional delivery system based on nanoparticles to target on pathological neuroinflammation. A drug delivery system is designed and generated using mesoporous silica nanoparticles (MSNs) that are loaded with Δ9-THC (Δ9-tetrahydrocannabinol, a cannabinoid) and ARA290 (an erythropoietin-derived polypeptide), both of which possess analgesic and anti-inflammatory functions. The actions of such THC-MSN-ARA290 nanocomplexes depend on the enhanced permeability and retention of THC through nanosized carriers, and a redox-sensitive release of conjugated ARA290 peptide into the local inflammatory milieu. The biosafety and anti-inflammatory effects of the nanocomplexes are first evaluated in primary microglia in vitro, and further in a mouse model of chronic constriction injury. It is found that the nanocomplexes attenuate in vitro and in vivo inflammation, and achieve a sustained relief of neuropathic pain in injured animals induced by both thermal hyperalgesia and mechanical allodynia. Thus, a nanoparticle-based carrier system can be useful for the amelioration of chronic neuropathic pain through combinatorial drug delivery.
authors.affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 31006, Zhejiang, Hangzhou, P. R. China.
authors.forename: Junran
authors.initials: J
authors.lastname: Xie
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, 221004, P. R. China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, 221004, P. R. China.
authors.forename: Dongju
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 31006, Zhejiang, Hangzhou, P. R. China.
authors.forename: Jinning
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 31006, Zhejiang, Hangzhou, P. R. China.
authors.forename: Nianqiang
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 31006, Zhejiang, Hangzhou, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Bao
authors.affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 31006, Zhejiang, Hangzhou, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Zhejiang, Hangzhou, 310009, P. R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Yu
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D013759:Dronabinol / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006930:Hyperalgesia / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009437:Neuralgia / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry; D010084:Oxidation-Reduction; D059408:Pain Management / Q000379:methods; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D009842:Oligopeptides; D012822:Silicon Dioxide; D013759:Dronabinol; C576178:cibinetide
keywords: ARA290; CCI; cannabinoids; mesoporous silica particles; multifunctional delivery; pain relief