Investigation of endocannabinoid-based nanoassemblies targeted to the synovium for the treatment of arthritis — ASN Events
  1. Schedule
  2. Poster Session One & Burnet Oration Cocktail Function
  3. Investigation of endocannabinoid-based nanoassemblies targeted to the synovium for the treatment of arthritis

Investigation of endocannabinoid-based nanoassemblies targeted to the synovium for the treatment of arthritis (#158)

Nicola Barrie 1 , Marina Ali 2 , Minoo Moghaddam 3 , Nicholas Manolios 1
  1. Rheumatology, Westmead Hospital, Sydney, NSW, Australia
  2. Dermatology, Westmead Hospital, Sydney, NSW, Australia
  3. Manufacturing, CSIRO, Sydney, NSW, Australia

BACKGROUND:

A series of endocannabinoid agonists with the ability to self-assemble into a variety of nanoassembled particles for the encapsulation and controlled release of drugs have been synthesised. Conjugation of a synovium targeting peptide, HAP-1 to the surface of the nanoparticles was added, facilitating their selective accumulation to the inflamed synovium. These targeted endocannabinoid-based nanoparticles were then evaluated for their anti-inflammatory effects in arthritic rats.

METHODS:

To study the effects of endocannabinoid-nanoparticles on inflammatory cytokine production in vitro, rheumatoid arthritis fibroblast like cells (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 injected intravenously with endocannabinoid-nanoparticles and blood samples collected by the lateral tail vein at various time intervals. Quantification of inflammatory cytokines in circulating rat plasma was determined using bead-based immunoassay.

RESULTS:

We have shown that cannabinoid receptors CB1 and CB2 are expressed by human fibroblast like synoviocytes (FLS), and are up-regulated in an inflammatory state. Incubation of endocannabinoid-nanoparticles suppressed IL-6, NF-Kb and MMP-1 cytokines in-vitro. Similarly in-vivo, circulating GM-CSF and IL-6 plasma levels, noted to be up-regulated in arthritic rats, were suppressed in the endocannabinoid-nanoparticle treated groups. Using HPLC endocannabinoid lipids, OEA and LEA, were highly expressed in joints of the nanoparticle injected rats and correlated with increases in endogenous PEA levels.

DISCUSSION:

Increasing evidence from preclinical studies supports the interest of the endocannabinoid system as an emerging therapeutic target for arthritic pain. We have shown that RA-FLS cells express endocannabinoid receptors which can regulate cytokine production in vitro and in vivo. The data suggests possible therapeutic potential in alleviating inflammation associated with arthritis.

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