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.
A multifunctional drug delivery system using mesoporous silica nanoparticles that are loaded with Δ9-THC (Δ9-tetrahydrocannabinol) and ARA290 (an erythropoietin-derived polypeptide) is designed. This system attenuates in vitro and in vivo inflammation in an experimental neuropathic animal model, and achieves a sustained relief of injured animals from neuropathic pain induced by both thermal hyperalgesia and mechanical allodynia.