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A step toward more effective treatment of osteoarthritis

 


A step toward more effective treatment of osteoarthritis

In vivo image credit of mouse knee joint obtained from Bruker © Xtreme II 7 days after intra-articular injection of (a) Cy7 free dye and (b) Cy7 labeled PLGA microparticles Credit: Kaamini M Dhanabalan

Researchers at the Indian Institute of Science (IISc) have developed a microparticle formulation that enables sustained release of a therapeutic agent for osteoarthritis, a chronic joint disease.

They designed a polymer matrix made of FDA-approved biomaterial poly(lactic-co-glycolic acid) or PLGA to encapsulate the immunosuppressant rapamycin. Preliminary studies on cells cultured in laboratory and mouse models have shown promising results showing reduced inflammation. By sustained drug release.

“In cell studies, PLGA microparticles loaded with rapamycin can release drugs for up to 21 days, and in animal studies PLGA microparticles “Up to 30 days after injection of microparticles into the knee joint of mice” is a Ph.D. student of Kaamini M Dhanabalan at the Center for Biosystems Science and Engineering (BSSE) at IISa and the first author of a study published in the journal. Biomaterial science..

Osteoarthritis is associated with the wear of cartilage, the smooth tissue that protects the joints of bones, caused by stress and aging. Current treatment plans focus more on managing pain and inflammation than treating disease. Although several classes of drugs appeared promising in preclinical trials, low drug retention and rapid clearance from target sites made clinical translation difficult.

However, the formulation developed by the IISC team has a maximum residence time of 30 days at the target site, with no obvious signs of potentially discomforting patients. Such sustained release systems can improve patient compliance and reduce outpatient visits.

PLGA is widely used in drug delivery applications and several drug formulations are currently used in the clinic. Rapamycin is commonly used to suppress the immune response in patients undergoing surgery for organ transplants to prevent organ rejection. Preclinical studies show therapeutic potential Prevents cell loss and cartilage damage, thereby reducing inflammation. However, due to the short drug residence time of 1-4 hours, frequent injections are required to maintain the therapeutic window of the joint. Therefore, Danabalan and her colleagues have combined the benefits of PLGA and rapamycin to create a system that allows sustained release. .. This was achieved by encapsulating rapamycin in PLGA microparticles.

To evaluate the efficacy of this formulation, chondrocytes or chondrocytes were cultured and subjected to various stresses to reproduce osteoarthritis-like conditions under laboratory settings. This resulted in pathological chondrocytes with features of osteoarthritis. These injured chondrocytes recovered from osteoarthritis when treated with rapamycin-loaded PLGA microparticles.

Rachit Agarwal, associate professor at BSSE and IISC, said: First author of the study.


Immunomodulators improve periodontal disease in mice


For more information:
Kaamini M. Dhanabalan et al. Rapamycin-PLGA microparticles prevent aging, maintain cartilage matrix production under stress, and exhibit long-term retention in mouse joints. Biomaterial science (2020). DOI: 10.1039 / d0bm00596g

Quote: A step toward more effective treatment of osteoarthritis (July 6, 2020)

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