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6 Articles in this Series
Introduction
Antibody Biomarker Predicts Abatacept Efficacy
Early Infection May Lead to Ankylosing Spondylitis
Gene Testing May Predict RA Treatment Response
JIA Patients at Higher Risk for Type 1 Diabetes
Nanotechnology Could Improve Rheumatoid Arthritis Treatments
Women With Lupus at Risk for Cervical Cancer

Nanotechnology Could Improve Rheumatoid Arthritis Treatments

With a growing armamentarium of tumor necrosis factor inhibitors (TNFi) and disease modifying antirheumatic drugs (DMARDs) now entering the market, doctors have many therapeutic options to choose from for the treatment of rheumatoid arthritis (RA).

But despite the strides made in drug development, disease management still suffers from challenges that oftentimes limit patient outcomes. Few patients can achieve disease remission without continuous pharmacological treatment, which is prone to its own adversities and toxicities, and many patients can develop tolerances to the medications or not respond to them altogether.

The search for a controlled, specified way to deliver therapeutic agents is fast becoming a burgeoning area of innovation, as researchers are now developing nanosystems capable of delivering drugs directly to sites of the inflammation. One such technology are targeted biodegradable nanoparticles (tBNPs), tiny particles of polylactic acid that can be used to not only deliver therapeutic agents to specific inflammation sites, but also help detect those very sites of inflammation, which would aid timely and accurate diagnoses of RA. This technology could allow clinicians to use drugs previously deemed too toxic.1

A team of Italian researchers presented compelling evidence of the technology’s ability to target and treat specific sites of inflammation.2 The results could be a major step forward to bringing the technology into clinical trials.

Targeting Inflammation Through Nanotechnology

Researchers are studying nanosystems capable of delivering drugs directly to the site of inflammation.Made of polylactic acid, polycaprolactone, and polyethylene glycol, these polymeric biodegradable nanoparticles are coated with a peptide capable of targeting inflamed synovial tissue exclusively. Through a series of tests, researchers conducted in  vitro assay and in vivo analysis to study the agent’s toxicity and efficacy in 2 different animal models: a rat model of antigen-induced arthritis (AIA) and a mouse model of collagen-induced arthritis (CIA).

Using immunofluorescence technique, researchers were able to see how fluorescent-tBNPs bound to inflammation sites. They found that after treating the rats and mice with tBNPs loaded with methotrexate (MTX), a standard-bearer of immunosuppressants traditionally used in RA management, tBNPs could bind specifically to inflamed synovial tissue in both in vitro and in vivo settings.

The targeting also appeared to be severity-dependent, binding according to the degree of inflammation. This suggests that tBNPs could be vehicles for delivering targeted therapies and be utilized as diagnostic tools. By filling the nanoparticles with a contrast agent, such as gadolinium (or iron complexes), tBNPs could help reveal sites of inflammation, enabling more accurate diagnosis and subsequent treatment courses, noted the authors.

High Methotrexate Efficacy Using tBNPs

With just one injection of tBNPs filled with MTX, a complete abrogation of the inflammatory process was observed in the acute AIA rat model, noted the researchers. By contrast, a regular dose of MTX was deemed completely ineffective. Similar results were found in the mouse model of chronic CIA, where a single tBNP injection infused with MTX was more effective than a dose of free MTX. No toxic effect was observed, the authors noted.

Unfortunately, the study results made no mention of the time course it took for the single tBNP injection to completely abrogate the synovial inflammation. There was also no mention of whether other therapeutic agents could be incorporated into the technology besides MTX.

According to Dr. Paolo Macor, lead investigator of the study from the Department of Life Sciences at the University of Trieste in Italy, moving away from reliance on systemic administration of therapeutic agents could be a major step forward for RA management. This combined with early diagnoses of RA could be a crucial step to achieving optimal patient outcomes and prognosis with RA, something clinicians are struggling to achieve currently.3

“There is therefore a need to develop a new tool to enable early diagnosis, and also to develop tissue-specific agents able to reduce systemic side effects. This would increase the potency of the drug with lower doses, and also potentially reduce the cost of treatment,” said Dr. Macor.

“The advantage of being able to deliver methotrexate in this targeted way is to be able to gain the benefits from this key treatment of RA, while reducing the risk of adverse effects that are more frequent at high doses.”

The successes of these animal model studies may form a basis for further research into other RA treatment, including the variety of TNFi drugs now available, noted the researchers. While having promising efficacy, TNFi drugs are known for carrying inherent risks and prohibitive costs. But using tBNPs to perform selective application of TNFi agents to targeted inflamed synovium could help limit these risks and costs, which could be a major step forward to optimizing pharmacological interventions for RA, said Dr. Macor.4

Study author L. Nunez is an employee of Biotarget. The rest of the study authors associated with this research declared no competing conflicts of interest.

References

  1. Pham CT. Nanotherapeutic approaches for the treatment of rheumatoid arthritis. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2011;3(6):607-619.
  2. Colombo F, Nunez L, Durigutto P, et al. Targeted Polymeric Nanoparticles as Diagnostic and Therapeutic Tool for Rheumatoid Arthritis. Presented at: Annual Meeting of the European League Against Rheumatism (EULAR); June 8-11, 2016; London, England.
  3. Nell V, Machold KP, Eberl G, et al. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford). 2004;43:906-914.
  4. Macor P. Development of nanoparticles specific for inflamed synovial tissue. http://dsv.units.it/en/research/researchareas/researchgroups/18231. Accessed July 1, 2016.
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