Stealth liposomes containing zoledronic acid for the treatment of neuropathic pain.

Purpose. The aim of this work was to develop nanosystems for the use of zoledronic acid (ZOL) in the treatment of symptoms associated with neuropathic pain and to assess the potential antineuropathic effect and the potential targets in the spinal cord (neurons, astrocytes, microglia). Materials and methods. PEGylated liposomes containing ZOL (lipoZ) were prepared by the reverse phase evaporation technique followed by extrusion, purification and lyophilization. The effectiveness of lipoZ was evaluated in an animals model of peripheral neuropathy, spared nerve injury (SNI). In particular, we evaluated the effects of lipoZ on mechanical allodynia. Finally, morphological assessments at the dorsal horn of the spinal cord (L4-L6) were made to investigate a potential action of lipoZ on reactive gliosis associated with neuropathic pain. Results. LipoZ with mean diameter of about 241 nm and an actual loading of ZOL between about 101 ???g ZOL/mg lipids were prepared. In vivo studies showed a significant reduction of mechanical allodynia after treatment with lipoZ; the treatment with free ZOL and blank liposomes were not produced any effect. The morphological analysis of the spinal cord of neuropathic mice, after treatment with blank liposomes, showed a change in the morphology of the astrocytes, as they are hypertrophied in the dorsal horn; this hypertrophy was not observed in mice treated with lipoZ. In addition, treatment with lipoZ produced an increase of IL-10, an anti-inflammatory cytokine, in astrocytes. Conclusions. For the first time, through the use of nanotechnology, the activity of ZOL for the treatment of neuropathic pain was demonstrated in vivo.