Recent advances in targeted drug delivery for treatment of osteoarthritis

Abstract

Purpose of review Osteoarthritis is associated with severe joint pain, inflammation, and cartilage degeneration. Drugs injected directly into intra-articular joint space clear out rapidly providing only short-term benefit. Their transport into cartilage to reach cellular targets is hindered by the tissue's dense, negatively charged extracellular matrix. This has limited, despite strong preclinical data, the clinical translation of osteoarthritis drugs. Recent work has focused on developing intra-joint and intra-cartilage targeting drug delivery systems (DDS) to enable long-term therapeutic response, which is presented here. Recent findings Synovial joint targeting hybrid systems utilizing combinations of hydrogels, liposomes, and particle-based carriers are in consideration for pain-inflammation relief. Cartilage penetrating DDS target intra-cartilage constituents like aggrecans, collagen II, and chondrocytes such that drugs can reach their cellular and intra-cellular targets, which can enable clinical translation of disease-modifying osteoarthritis drugs including gene therapy. Summary Recent years have witnessed significant increase in both fundamental and clinical studies evaluating DDS for osteoarthritis. Steroid encapsulating polymeric microparticles for longer lasting pain relief were recently approved for clinical use. Electrically charged biomaterials for intra-cartilage targeting have shown promising disease-modifying response in preclinical models. Clinical trials evaluating safety of viral vectors are ongoing whose success can pave the way for gene therapy as osteoarthritis treatment.

Resveratrol and Curcumin AttenuateEx VivoSugar-Induced Cartilage Glycation, Stiffening, Senescence, and Degeneration

“…53 This can be overcome by delivering drugs using optimally charged cationic carriers that utilize electrostatic interactions to enhance their targeting, uptake and retention within the negatively charged cartilage. 53 -58 AGE accumulation within cartilage reduces GAG release levels ( Figs. 1f , 2f , and 6d ) and is associated with the loss of primary amines on collagen II, which can increase the tissue’s net negative fixed charge density (FCD).…”

Nanotheranostics-An Emerging Technique in Nanomedicine

“…is overexpressed [60]. To make these particles work for enzyme-based diagnostics, MMP-13 peptide which were cleavable plus near-infrared Nir dye cy5.5 and quencher were conjugated [61].…”

Stimuli‐Sensitive Nanotherapies for the Treatment of Osteoarthritis

“…There is an increasing requirement of prompt and effective OA treatments due to the limited self‐regenerative capacity of cartilage. [ 21 ] Current clinical therapies for OA mainly focus on pain relief, delaying the development of arthritis, and improving joint mobility, which cannot reverse the progress of OA. [ 18,22 ] Clinical treatments for OA are divided into non‐pharmacological, pharmacological, and surgical management.…”