Advanced Nanocarriers for Delivering Traditional Chinese Medicine Monomers in Rheumatoid Arthritis: Prospects and Challenges

Abstract: Rheumatoid arthritis (RA) is an auto-immune disease that is accompanied by constant inflammation and degradation of joints, causing disabilities and poor quality of life. Even though the available therapies alleviate symptoms, long-term use is often linked with loss of effectiveness, systemic toxicity, and poor patient compliance. Recently, bioactive monomers that can be extracted from Traditional Chinese Medicine (TCM) gained attention due to their anti-inflammatory, immunomodulating and antioxidant effects. Nonetheless, their implementation into treatment is hindered by poor aqueous solubility, bioavailability, fast elimination and uncertain pharmacokinetics. Nanotechnology-based drug delivery systems present novel and efficient solutions for overcoming these problems through enhanced delivery and effectiveness of TCM monomers. Examples of such systems include polymeric nanoparticles, liposomes, micelles and hydrogels. Apart from traditional approaches, new platforms such as stimuli responsive and biomimetic nanocarriers are receiving increased interest due to their ability to provide on-demand drug release and biological interactions in the inflammatory environment of synovium. Additionally, nanotechnology offers a platform for combination treatments via delivering several agents or combining with traditional anti-rheumatic medications. It should be mentioned that at present, most evidence is obtained based on preclinical in vitro and in vivo studies and does not include clinical trials. The aim of this review is to analyze recent progress in nanocarrier-based delivery of TCM monomers for the treatment of RA in terms of their abilities to improve bioavailability, enhance pharmacological effects and modulate inflammatory pathways. In contrast to existing literature reviews which mainly describe individual systems of nanocarriers, this study compares multiple delivery systems along with their limitations in translation. Moreover, current problems, namely safety issues, scalability, regulatory aspects, and clinical translation are thoroughly analyzed. Thus, nanocarrier-based approaches can be considered as perspective tools for improving RA treatment, but require further clinical validation. Keywords: rheumatoid arthritis, nanocarriers, traditional chinese medicine, targeted drug delivery, bioavailability