Madeline Franke

Introduction: Osteoarthritis (OA) is a debilitating, degenerative joint disease that affects approximately 250 million people worldside¹. OA is a leading cause of physical disability and its risk increases with factors such as age, obesity, and joint injury^1,2. OA involves a mismatch between the anabolism and catabolism of cartilage and other tissues, which leads to the accumulation of degradation products and subsequent inflammation in the joint space^,4. There are currently no disease-modifying treatments for OA and delivery of pharmacological therapy for symptomatic relief has proven to be challenging^2,3,4. Microparticle drug delivery systems are currently being researched as a novel mechanism in which to treat OA⁴. These drug delivery systems have the potential to provide a way to allow for the slow, sustained release of drugs directly to the affected joint, while bypassing systemic exposure^3,4. Methods: Polymeric microparticles were fabricated using various techniques and embedded with different drugs to assess their efficacy with a wide gamut of pharmacological treatment⁵. Microparticle size and morphology was assessed using technologies such as scanning electron microscopy⁵. The drug-release profiles and cell toxicity of microparticle drug delivery systems were investigated using in vitro tests⁵. In vivo models, such as murine models, were used to assess microparticle residence time in a joint and effects of the microparticles on living tissues⁵. Results: Higher molecular weight poly(lactic-co-glycolic acid) microparticles in a 65:35 polylactic acid – polyglycolic acid ratio allowed for the slowest, most sustained release of various drugs⁵. Additionally, the size range of 900nm – 1mm diameters are most desirable for biodegradation and drug delivery⁵. One work emphasized that the use of a microfluidic fabrication method resulted in more heterogenous microparticles, which was advantageous for drug delivery⁶. The in vitro analyses demonstrated that drug-loaded microparticles could sustain sulphated-glycosaminoglycans (sGAG) production by chondrocytes in oxidative and genotoxic stress situations, showing how these embedded-microparticles were therapeutic for damage caused by OA⁵. These in vitro assessments further displayed how the microparticles demonstrate cytocompatibility^6,7. In vivo models in various works demonstrated how microparticles allowed for the increased residence time and half life compared to free drug⁵. Conclusions: Currently, there is a need for a way to deliver OA pharmacological therapy directly to the joint site without entering systemic circulation^3,4. Additionally, this delivery needs to provide sustained, high doses of a drug that avoids lymphatic clearance^3,4. Microparticle drug delivery systems are novel treatment options that can solve all the challenges posed by administering current OA drugs⁴.

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2. DeJulius CR, Gulati S, Hasty KA, et al. Recent Advances in Clinical Translation of Intra‐Articular Osteoarthritis Drug Delivery Systems. Advanced Therapeutics. 2021;4(1):2000088. doi: 10.1002/adtp.202000088.
3. Salgado C, Jordan O, Allemann E. Osteoarthritis In Vitro Models: Applications and Implications in Development of Intra-Articular Drug Delivery Systems. Pharmaceutics. 2021;13(1):60.
4. Castro LM, Garcia AJ, Guldberg RE. Biomaterial strategies for improved intra-articular drug delivery. Journal of biomedical materials research. 2021;109(4):426-436. doi: 10.1002/jbm.a.37074.
5. Dhanabalan KM, Gupta VK, Agarwal R. Rapamycin-PLGA microparticles prevent senescence, sustain cartilage matrix production under stress and exhibit prolonged retention in mouse joints. Biomaterials Science. 2020;8:4308–4321. doi: 10.1039/D0BM00596G.
6. Zhu C, Yang H, Shen L, Zheng Z, Zhao S, Li Q. Microfluidic preparation of PLGA microspheres as cell carriers with sustainable Rapa release. Journal of Biomaterials Science, Polymer Ed. 2019;30(9):737-755. doi: 10.1080/09205063.2019.1602930.
7. Salgado C, Guénée L, Černý R, Allémann E, Jordan O. Nano wet milled celecoxib extended release microparticles for local management of chronic inflammation. International Journal of Pharmaceutics. 2020;589(119783).