Intra-articular targeting of nanomaterials for the treatment of osteoarthritis

Abstract

Osteoarthritis is a prevalent and debilitating disease that involves pathological contributions from numerous joint tissues and cells. The joint is a challenging arena for drug delivery, since the joint has poor bioavailability for systemically administered drugs and experiences rapid clearance of therapeutics after intra-articular injection. Moreover, each tissue within the joint presents unique barriers to drug localization. In this review, the various applications of nanotechnology to overcome these drug delivery limitations are investigated. Nanomaterials have reliably shown improvements to retention profiles of drugs within the joint space relative to injected free drugs. Additionally, nanomaterials have been modified through active and passive targeting strategies to facilitate interactions with and localization within specific joint tissues such as cartilage and synovium. Last, the limitations of drawing cross-study comparisons, the implications of synovial fluid, and the potential importance of multi-modal therapeutic strategies are discussed. As emerging, cell-specific disease modifying osteoarthritis drugs continue to be developed, the need for targeted nanomaterial delivery will likely become critical for effective clinical translation of therapeutics for osteoarthritis.

Leveraging Electrostatic Interactions for Drug Delivery to the Joint

“…Changes in joint tissues with progression of arthritis and changes in opportunities for targeting using electrostatic interactions in each of the major tissue types. Adapted from Brown et al 47 d-glucuronic acid, is a high-molecular-weight, negatively charged polysaccharide and major component of synovial fluid. Investigators have targeted the anionic charge of the synovial fluid with cationic carriers as a method to improve their residence time with the joint.…”

“…46 As previously mentioned, another major limitation of intra-articular injections is often the limited residence time of the therapeutic within the joint space after injection. 47 The unique barriers posed by each joint tissue to localization and uptake of therapeutics are also often overlooked when designing drugs for intra-articular delivery. 47 For instance, cartilage, a target of interest in joint preservation, comprises a spare population of cells within a dense avascular ECM.…”

“…47 The unique barriers posed by each joint tissue to localization and uptake of therapeutics are also often overlooked when designing drugs for intra-articular delivery. 47 For instance, cartilage, a target of interest in joint preservation, comprises a spare population of cells within a dense avascular ECM. When faced with such tissue barriers, drugs are unable to reach their intra-tissue target sites at 84 KUMAR AND SHARMA optimal doses for clinical efficiency.…”

Current Strategies for the Treatment of Early Stage Osteoarthritis

“…For the past few years, a better understanding of OA has progressed from the definition of primarily a non-inflammatory disease of articular cartilage to a broader concept of a lowgrade inflammatory disease affecting all synovial joint tissues, such as articular cartilage, synovium as well as the underlying subchondral bone (Gupta et al, 2012;Barry and Murphy, 2013;Brown et al, 2019). As such, OA is considered as a degenerative whole-joint disease and all synovial joint tissues actively participate in the progression of this disease.…”

Preparation and characterization of novel anti-inflammatory biological agents based on piroxicam-loaded poly-ε-caprolactone nano-particles for sustained NSAID delivery

“…One of the solutions to prolonged local treatment with NSAIDs is the use of IA sustained drug delivery system (Zhang et al, 2018). Most important one of these systems is polymer-based nanoparticle (NP) system that acts as drug carriers to decrease the rapid withdrawal of different therapeutic agents such as drugs from the synovial cavity and increase drug retention time in the joints after IA administration (Mitragotri & Yoo, 2011;Kim et al, 2015;Brown et al, 2019). Between the various biodegradable polymers, poly-e-caprolactone (PCL) has been considered as a drug carrier due to its good properties, such as biodegradability, biocompatibility, and high permeability to micro-molecular drugs (Mei et al, 2018;Zupan ci c et al, 2018;.…”