Background:
We have synthesized a series of endocannabinoid-based nanoparticles for the encapsulation and controlled release of drugs. We have shown, nanoparticle incorporation of a synovium targeting peptide; HAP-1 facilitates the selective accumulation of nanoparticles to the inflamed synovium. Furthermore, increasing evidence from preclinical studies supports the interest of the endocannabinoid system as an emerging therapeutic target for arthritic pain. We have shown that cannabinoid receptors are expressed by human fibroblast like synoviocytes (FLS), and are upregulated in an inflammatory state. Interaction of nanoparticle endocannabinoid lipid constituents facilitates the potential for joint pain relief via local manipulation of the endocannabinoid system present in the synovium of RA patients. This study aims to evaluate the anti-inflammatory potential of endocannabinoid-based nanoparticles in arthritic rats.
Methods:
To study the effects of endocannabinoid-nanoparticles on inflammatory cytokine production, RA-FLS cells were stimulated with TNF-α alone, or in the presence of endocannabinoid-nanoparticles. Pro-inflammatory gene expression was measured by PCR. In-vivo, arthritic rats were I.V injected with endocannabinoid-nanoparticles and blood collected at various time intervals. Quantification of inflammatory cytokines in circulating rat plasma was determined using bead-based immunoassay.
Results and Conclusions:
Incubation of endocannabinoid-nanoparticles suppressed pro-inflammatory upregulated IL-6, NF-Kb and MMP-1 cytokines in-vitro. Similarly in-vivo, GM-CSF and IL-6 plasma levels previously upregulated in arthritic rats were suppressed in endocannbinoid-nanoparticle treated groups. Endocannabinoid lipids, OEA and LEA, were highly expressed in nanoparticle injected rats and correlated well with increases in endogenous PEA levels. The data suggests possible therapeutic potential in alleviating inflammation and inflammatory pain associated with arthritis.