Polymeric Hydrogels for Controlled Drug Delivery to Treat Arthritis

Abstract

Rheumatoid arthritis (RA) and osteoarthritis (OA) are disabling musculoskeletal disorders that affect joints and cartilage and may lead to bone degeneration. Conventional delivery of anti-arthritic agents is limited due to short intra-articular half-life and toxicities. Innovations in polymer chemistry have led to advancements in hydrogel technology, offering a versatile drug delivery platform exhibiting tissue-like properties with tunable drug loading and high residence time properties This review discusses the advantages and drawbacks of polymeric materials along with their modifications as well as their applications for fabricating hydrogels loaded with therapeutic agents (small molecule drugs, immunotherapeutic agents, and cells). Emphasis is given to the biological potentialities of hydrogel hybrid systems/micro-and nanotechnology-integrated hydrogels as promising tools. Applications for facile tuning of therapeutic drug loading, maintaining long-term release, and consequently improving therapeutic outcome and patient compliance in arthritis are detailed. This review also suggests the advantages, challenges, and future perspectives of hydrogels loaded with anti-arthritic agents with high therapeutic potential that may alter the landscape of currently available arthritis treatment modalities.

Functionalized Hydrogels for Cartilage Repair: The Value of Secretome-Instructive Signaling

“…The diffusion rate of solutes, enzymes, factors, and other elements in the hydrogel depends on the relationship between the size of the molecule/particle and the mesh size of the polymer network [ 118 , 120 ]. Thus, the hydrogel porosity, which is related to its mechanical and physicochemical properties (swelling ratio, degradation resistance), influences the degradability rate of the hydrogel [ 121 , 122 ], nutrient diffusion, transport of oxygen, removal of toxic components, as well as the cell proliferation, migration, and adhesion [ 3 , 41 , 121 , 122 , 123 ].…”

“…Therefore, by modulating the mesh size, swelling, and degradability rate, it is possible to produce hydrogels capable of stabilizing molecules and other bioactive factors and releasing them in a controlled manner, enhancing and tuning the regenerative process. Different strategies have been developed to tailor the hydrogel features to deliver immunomodulatory and pro-regenerative molecules and factors in a controlled manner, which have been extensively reviewed elsewhere [ 118 , 120 , 124 ]. Some examples of the association between hydrogels with GFs and EVs and their release times are summarized in Table 1 and will be discussed in the next sections.…”

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

“…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 ].…”

“…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 ]. When the innate immune system recognizes the presence of damaged tissue, it activates the signalling pathways to produce proinflammatory effectors such as cytokines, chemokines, and prostanoids [ 5 , 6 , 7 ].…”

“…However, its main disadvantage is that drugs are rapidly eliminated from the site of administration. This implies that multiple applications are required for an adequate therapeutic effect [ 3 , 7 ]. Consequently, repeated administration often leads to discontinuation of treatment by patients.…”