A comprehensive review of nanotechnology based drug delivery systems for osteoarthritis treatment

The complex etiology and short-term positive effects of treatments for osteoarthritis (OA) remain a significant challenge globally. The lack of approved disease-modifying OA drugs (DMOADs) and the rapid clearance of intra-articular (IA) injections limit the treatment outcomes. Moreover, traditional therapy showed symptomatic relief and was limited by an accurate target and low drug bioavailability. In this view, nanotechnology-based drug delivery systems have been developed as a potential method to optimise therapeutic efficacy, targeted delivery, and minimise side effects in OA. These technologies provide better outcomes in regulating critical molecular pathways associated with OA progression, including the suppression of matrix metalloproteinases, inflammatory cytokines, and indicators of cartilage breakdown. A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Embase using the keywords OA, drug delivery, biomaterials, and other nanocarriers, including nanoparticles, liposomes, and hydrogels, covering preclinical studies, clinical trials, and systematic reviews. The literature review presents current developments in nanocarriers and their applications for enhancing drug penetration and controlled release in joint tissues. Moreover, we emphasised the significance of nanocarrier-based drug delivery systems, including liposomes, micelles, dendrimers, and nanoparticle-based hydrogels, which are specifically engineered for OA treatment. The key findings indicated that nanocarriers can be designed to specifically target cartilage components, including aggrecans and collagen II, while effectively delivering various therapeutics such as anti-inflammatory agents, disease-modifying drugs, and gene therapies. Nanomicelles, nanohydrogels, and extracellular vesicles enabled optimised drug delivery to the specified target. The nanocarrier piroxicam gel was more effective at relieving pain due to its enhanced transdermal penetration. Oral nanomicelle-curcumin has reduced pain and stiffness compared with placebo. Nevertheless, challenges, including the reliability of biocompatibility, reduction of toxicity, and precise targeting, must be resolved to exploit their potential. Although preliminary clinical results with topical and oral nanoformulations are promising, future research should focus on long-term safety and on developing IA nanotherapies that demonstrate sustained release and chondroprotective properties.