A Critical Review on Glycosaminoglycan Derived Polymers as a Novel Drug Delivery System in Tissue Engineering: Recent Advancement and Clinical Application

Glycosaminoglycans (GAGs), natural components of the extracellular matrix, exert significant influence over cellular function and regulate the microenvironment surrounding cells. This characteristic makes them promising targets for therapeutic intervention across a spectrum of diseases. In the realm of medical research, there has been a longstanding quest for precise and targeted drug delivery methods to mitigate adverse effects and enhance the efficacy of treatments for conditions, such as wounds, cancer, and organ disorders. However, implementing a systemic delivery approach, particularly for protein-based therapeutics, poses challenges. Addressing this challenge requires the development of biocompatible materials capable of efficiently encapsulating and releasing therapeutic proteins. GAGs emerge as promising candidates possessing these desirable attributes, given their bioderived nature and ability to modulate biological responses. Within the realm of GAGs, various linear polysaccharides exhibit diverse functionalities and payloads. Notably, hyaluronic acid (HA) and chondroitin sulfate (CS) have been utilized as polysaccharide-based biomaterials for drug delivery, particularly in the treatment of rheumatoid arthritis. Modified HA and CS can self-assemble into micelles or micellar nanoparticles (NPs), enabling precise and controlled drug delivery. This paper explores a range of NP formulations derived from HA and CS, including drug conjugates, polymers, small molecules, polyelectrolyte nanocomplexes (PECs), metals, and nanogels. The versatility of these NP formulations extends to various therapeutic applications, including cancer chemotherapy, gene therapy, photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and immunotherapy. By harnessing the unique properties of HA and CS, these NP-based systems offer promising avenues for advancing therapeutic interventions in diverse clinical settings.