Abstract
The current treatment strategies for neuropathic pain are only partially effective at best. There is a drive to find more effective treatments for chronic forms of pain such as neuropathic pain. Cannabinoids are drugs that are derived from the cannabis plant or mimic the effects or structure of plant-derived cannabinoids. Cannabinoids are moderately effective in the treatment of neuropathic pain. Previous research has investigated several ways of selectively targeting the different cannabinoid receptors to avoid psychoactive side effects. Selective targeting has been unsuccessful as cannabinoids are highly lipophilic and readily enter the brain causing side effects. Current research has shown that different receptor selective cannabinoids typically produce side effects at the therapeutic doses required to treat neuropathic pain.
The research in this thesis investigated the use of nanotechnology for the synthesis of water soluble nanoparticles containing the potent cannabinoid WIN 55,212-2 (WIN). The drug was created to selectively target the site of inflammation in the spinal cord caused by neuropathic pain, while failing to pass through the blood brain barrier. The cannabinoid WIN was successfully encapsulated inside a styrene maleic acid (SMA) based micelle. The now water soluble micelles were assessed for size and release to ensure adequate properties. Of the micelles produced, a loading of 21 % WIN to SMA was decided on for the behavioural studies, due to this loading of micelle having slow release properties and a large diameter. The large size ensured that the micelle would remain in the circulation and not pass fenestrations of the kidneys. The large diameter also ensured they should not pass the blood brain barrier and produce side effects. The release properties of the micelle suggested that it would be relatively stable within the circulation. These properties of enhanced permeability and retention effect were expected to allow the micelles to bioaccumulate in the area of inflammation in the spinal cord.
Using the chronic constriction injury model of sciatic neuropathy, the SMA-WIN micelles were efficacious in the treatment of neuropathic pain for a prolonged period of time compared to the positive control WIN. Pain relief occurred for up to 8 hours at a dose of 11.5 mg/kg of SMA-WIN micelle. To evaluate cognitive impairment the rotarod assessment was utilised. Results showed initial impairment caused by SMA-WIN micelles to be identical to WIN controls for up to 1.5 hours. These results probably indicate motor impairment from an initial release of WIN from the micelle. However, the SMA-WIN micelle was still able to produce prolonged analgesia with decreased side effects compared to the fat soluble cannabinoids.
The effectiveness of the nanotechnology for the treatment of neuropathic pain is promising. This study has found that the formulation of nanoparticles for the treatment of neuropathic pain may be an exciting new field of research and should be investigated further.