Emerging intra-articular drug delivery systems for the temporomandibular joint

Abstract

Temporomandibular joint (TMJ) disorders are a heterogeneous group of diseases that cause progressive joint degeneration leading to chronic pain and reduced quality of life. Both effective pain reduction and restoration of TMJ function remain unmet challenges. Intra-articular injections of corticosteroids and hyaluronic acid are currently used to treat chronic pain, but these methods require multiple injections that increase the risk of iatrogenic joint damage and other complications. The small and emerging field of TMJ tissue engineering aims to reduce pain and disability through novel strategies that induce joint tissue regeneration. Development of methods for sustained, intra-articular release of growth factors and other pro-regenerative signals will be critical for the success of TMJ tissue engineering strategies. This review discusses methods of intra-articular drug delivery to the TMJ, as well as emerging injectable controlled release systems with potential to improve TMJ drug delivery, to encourage further research in the development of sustained release systems for both long-term pain management and to enhance tissue engineering strategies for TMJ regeneration.

Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint

“…[1][2][3] The approach seeks to selectively deliver the agents to local tissues while minimizing overall systemic exposure. 1,2 However, the therapeutic outcome following IA injection is considerably lessened by drug delivery issues that include rapid clearance into the systemic circulation from the synovial ultrastructure, which offers little barrier to the diffusion of molecules in and out of a joint.…”

“…[1][2][3] The approach seeks to selectively deliver the agents to local tissues while minimizing overall systemic exposure. 1,2 However, the therapeutic outcome following IA injection is considerably lessened by drug delivery issues that include rapid clearance into the systemic circulation from the synovial ultrastructure, which offers little barrier to the diffusion of molecules in and out of a joint. 4,5 Knight and Levick 6 found that the synovial surface consists of a discontinuous layer of synoviocytes (covering 80% of the synovial lining) with wide intercellular gaps measuring 0.1-5.5 μm with no basal membrane.…”

Micro- and Nano-Carrier Mediated Intra-Articular Drug Delivery Systems for the Treatment of Osteoarthritis

“…The complications of such frequent injections in terms of infections or joint instability remain severe although rare. All these aspects emphasize the need to develop drug delivery systems allowing the sustained release of the active substance in order to reduce the frequency of the intra-articular injections together with the related potential deleterious effects [11].…”

“…However, current preparations of intra-articular drug delivery often require frequent injections that have a high financial burden, impaction to patient's quality of life, rapid degradation and clearance of injected pharmacologic agents, and also increase the risk of complications [11]. Micro-and nanocarrier-mediated drug delivery systems, including polymeric particles, liposome, and hydrogel, are well-established as methods for sustained release in intraarticular applications.…”

Cross-Linked Gelatin Microcapsules for Drug Delivery in a Arthritic TMJ

“…Alternatively, if drug delivery could be sustained after a single injection these risks from a multi-injection protocol could be minimized. A variety of methods have been tested for sustained drug delivery in a joint space, including encapsulating or incorporating drugs into nano-or microparticles consisting of organic polymers (Deasy, 1994;Mountziaris, Kramer & Mikos, 2009). In this report we test a crosslinked fluid filled gelatin capsule for intra-articular injection.…”