Designing a reliable method of delivering therapeutic agents when and directly to where they are needed has remained an ongoing challenge for arthritis researchers. Now, a new study demonstrates the promise of a drug-loaded hydrogel that releases its cargo in response to enzymes produced during arthritic flares.
“For inflammatory arthritis, where only one or a few joints are involved, local therapy with intra-articular injections may offer distinct advantages over systemic therapy, by increasing the drug concentration locally and reducing the potential for drug-induced systemic toxicity; however, direct injection into the joint is problematic as drugs are quickly cleared,” explains corresponding author Jeffrey Karp.
To address this problem, Karp and colleagues investigated the properties of triglycerol monostearate (TG-18), an amphiphilic molecule that is generally recognized as safe by the FDA and that self-assembles into a hydrogel that can carry several types of therapeutic agent and can disassemble in the presence of certain enzymes.
In vitro, TG-18 created a stable hydrogel that released its cargo of glucocorticoids in response to disease flare-associated enzymes at concentrations similar to those found in the synovial fluid of patients with rheumatoid arthritis (RA). The same response was also observed in response to synovial fluid from patients with RA, but not to synovial fluid from healthy individuals.
The research team then trialled the drug-loaded hydrogel in mice injected with either a medium or a high dose of K/B × N serum to induce moderate or severe inflammatory arthritis, respectively. Drug-loaded TG-18 suppressed disease in mice with moderate arthritis, whereas limited disease suppression was seen when glucocorticoid was administered alone. In addition, a single dose of drug-loaded hydrogel was able to suppress disease in mice with severe arthritis, suggesting that the drug-loaded hydrogel can elicit a long-term therapeutic effect.
a single dose of drug-loaded hydrogel was able to suppress disease in mice with severe arthritis
“We are interested in validating this approach in large animal models and exploring the potential of this platform to deliver biologics and other disease modifying therapeutics to affected joints,” concludes lead author Nitin Joshi.
Joshi, N. et al. Towards an arthritis flare-responsive drug delivery system. Nat. Commun. 9, 1275 (2018)
Rights and permissions
About this article
Cite this article
Collison, J. Drugs deliver themselves during flares. Nat Rev Rheumatol 14, 321 (2018). https://doi.org/10.1038/s41584-018-0014-8