Dr Meghna Takelar
|Recipient:||Dr Meghna Takelar|
|Intended department:||Jointly funded by the BB & A Miller Foundation and the ARA- The University of Queensland|
|Targeted oral liposomal microcomplexes for tolerizing dendritic cells in rheumatoid arthritis|
Autoimmune diseases such as rheumatoid arthritis (RA) affect 5% Australians and are a major health burden. Current therapies seldom provide drug-free long-lasting remission, with some treatments increasing patient susceptibility to opportunistic infections. Hence alternative therapies, which would rectify the underlying etiology, are essential for prevention and cure. We have explored strategies for co-delivering small doses of self-antigens (self-tissue) along with drugs in liposomes (tiny fat bubbles) to prevent the immune attack on self-tissue and hence treat RA. Currently, this therapy is provided as injections, which are less convenient than oral delivery from a long-term clinical perspective, especially if we wish to progress towards preventive strategies and treatment of children. Further the oral delivery system tends to maximize delivery to the gut immune system, which is ideal for prevention. With the support from Bruce Miller-ARA 2017 Grant, I have been able to develop oral particles, called microcapsules that can withstand the harsh conditions of the stomach and deliver intact liposomes to immune cells in the gut. The gut immune cells can process the drug they contain to suppress levels of disease-causing cells and increase numbers of cells, which would protect the body. In this fellowship, I aimed to extend the capabilities of these liposomes by designing targeted liposomes that will show preferential uptake by the intestinal cells called M-cells. These cells specialize in directing antigens to immune cells in the gut. This novel strategy will improve the delivery of the therapies to the desired sites in the intestine. I had also proposed an assessment of the particles in mouse models to enable progression to clinical trials.
With support from Arthritis Australia, we were able to procure an instrument (January 2018), which would enable reproducible preparation of our oral particles. Similarly, we were able to secure funding (September 2018) to obtain a microfluidizer instrument to prepare liposomes. Coupling the two instruments has now enabled us to prepare the oral particles efficiently with good reproducibility. I have been able to provide evidence that the microcapsules can protect the drug from the harsh conditions of the stomach, deliver it to immune cells in the gut and provide an appropriate immune response. I have also been able to prepare the targeted microcapsules and I have done initial studies to see how they distribute. In parallel, I have optimized the microcapsule parameters to enable assessment in mouse models of arthritis.
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