Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage

Abstract

Osteoarthritis (OA) is a progressive chronic inflammation that leads to cartilage degeneration. OA Patients are commonly given pharmacological treatment, but the available treatments are not sufficiently effective. The development of sustained-release drug delivery systems (DDSs) for OA may be an attractive strategy to prevent rapid drug clearance and improve the half-life of a drug at the joint cavity. Such delivery systems will improve the therapeutic effects of anti-inflammatory effects in the joint cavity. Whereas, for disease-modifying OA drugs (DMOADs) which target chondrocytes or act on mesenchymal stem cells (MSCs), the cartilage-permeable DDSs are required to maximize their efficacy. This review provides an overview of joint structure in healthy and pathological conditions, introduces the advances of the sustained-release DDSs and the permeable DDSs, and discusses the rational design of the permeable DDSs for OA treatment. We hope that the ideas generated in this review will promote the development of effective OA drugs in the future.

Synovial fluid profile dictates nanoparticle uptake into cartilage - implications of the protein corona for novel arthritis treatments

“…Nevertheless, our PEGylation strategy did not inhibit protein adhesion to the NPs in general, resulting in particle size increase and reduced zeta potential, likely arising from the negatively charged proteins present in SF and serum 10 . As intra-articular NP drug delivery systems shift from sustained-release to enhanced tissue penetration to target cartilage cells 20 , considerations of protein corona effects will play a substantial role from pre-clinical development to success in the clinics and the emerging field of personalized medicine 21 .…”

Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1

“…Increased amounts of inflammatory mediators and cartilage matrix-degrading enzymes are produced by chondrocytes during the progression of OA, leading to an imbalance between the production of anabolic vs. catabolic and inflammatory factors within the OA joint [ 4 ]. Current therapies for OA are limited, and there is a major unmet need for drugs and other treatment modalities which could enable the prevention, retardation or repair of cartilage degradation or injury [ 5 , 7 , 8 , 9 ].…”

Thermosensitive Injectable Hydrogels for Intra-Articular Delivery of Etanercept for the Treatment of Osteoarthritis

“…Osteoarthritis (OA) is the most prevalent chronic degenerative disease worldwide. It was estimated that globally 22.9% (corresponding to 654.1 million) of people over 40 years of age suffered from this disease in 2020 [ 1 , 2 ]. It is a disease that progressively affects the cartilage, synovial membrane, bone and periarticular tissues [ 2 , 3 , 4 ].…”

“…It was estimated that globally 22.9% (corresponding to 654.1 million) of people over 40 years of age suffered from this disease in 2020 [ 1 , 2 ]. It is a disease that progressively affects the cartilage, synovial membrane, bone and periarticular tissues [ 2 , 3 , 4 ]. In joint diseases such as OA, the inflammatory process is the response of the immune system to injuries and when this is not resolved in time it becomes a chronic disease, causing intense pain and damage to the joints and surrounding tissues [ 3 , 5 ].…”

“…Chitosan (CS) is a polysaccharide whose structure is highly similar to glycosaminoglycans that make up articular cartilage, so it has been frequently used in the development of hydrogels for intra-articular application. In addition, CS is a cationic, biocompatible, biodegradable polymer with marked mucoadhesive properties that are very useful for anchoring to surrounding tissue [ 2 , 23 , 24 ]. CS can also form gels by interacting with some salts such as phosphates, specifically with disodium β-glycerophosphate (BGP), to form thermosensitive hydrogels [ 25 , 26 ].…”