Management of osteoarthritis: From drug molecules to nano/micromedicines

Abstract

With the change in lifestyle and aging of the population, osteoarthritis (OA) is emerging as a major medical burden globally. OA is a chronic inflammatory and degenerative disease initially manifesting with joint pain and eventually leading to permanent disability. To date, there are no drugs available for the definitive treatment of osteoarthritis and most therapies have been palliative in nature by alleviating symptoms rather than curing the disease. This coupled with the vague understanding of the early symptoms and methods of diagnosis so that the disease continues as a global problem and calls for concerted research efforts. A cascade of events regulates the onset and progression of osteoarthritis starting with the production of proinflammatory cytokines, including interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α; catabolic enzymes, such as matrix metalloproteinases (MMPs)‐1, ‐3, and ‐13, culminating into cartilage breakdown, loss of lubrication, pain, and inability to load the joint. Although intra‐articular injections of small and macromolecules are often prescribed to alleviate symptoms, low residence times within the synovial cavity severely impair their efficacy. This review will briefly describe the factors dictating the onset and progression of the disease, present the current clinically approved methods for its treatment and diagnosis, and finally elaborate on the main challenges and opportunities for the application of nano/micromedicines in the treatment of osteoarthritis. Thus, future treatment regimens will benefit from simultaneous consideration of the mechanobiological, the inflammatory, and tissue degradation aspects of the disease. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

Biocompatible Amino-modificated Tantalum Nanoparticles with Catalase Activity for Sustained Intra-articular Reactive Oxygen Species Scavenging and Alleviation of MIA induced Osteoarthritis

“…Compared with traditional antioxidants, the stability analysis indicated that the H 2 O 2 scavenging of Ta-NH 2 NPs was not in uenced by pH or temperature [32]. It is well known that the activities of ROS scavenging in traditional biological enzymes [33] were affected by the microenvironment of joint cavity, and this drawback might affect the therapeutic outcome due to the uctuation in physical and chemical properties of osteoarthritic joints.…”

Quercetin prevents osteoarthritis progression possibly via regulation of local and systemic inflammatory cascades

“…Current therapeutic agents alter the OA pathogenesis by targeting the regulation of inflammatory processes or the expression of growth factors or aggrecans. 46 , 47 Articular cartilage, an avascular tissue that forms the articulating surface of all joints, possesses an ECM to support normal biomechanics and homeostatic properties of joint cartilage. Cartilage is unique due to its limited regenerative ability and avascular nature.…”

Analysis of Nanomedicine Efficacy for Osteoarthritis

“…A number of drugs have been approved by the US Food and Drug Administration (FDA) to treat OA, such as Diclofenac, Celecoxib, and Flurbiprofen, [ 106 ] as well as nucleic acids like short interfering RNA (siRNA) that downregulate proinflammatory factors and protein‐degrading enzymes, but there are cases of rapid clearance by intra‐articular synovial fluid, resulting in inefficiency. [ 107 ] Nanomaterials with their scale advantage are a good carrier option to improve cargo stability and even achieve targeted therapies. [ 108 ] Conventional NP carriers can be divided into lipid‐based NPs, polymeric NPs, inorganic NPs, and a special nanocarrier derived from endogenous exosomes of animals and human body.…”