Hyaluronic acid–based systems for brain drug delivery: bridging material design and cellular response

Introduction: Over the past decade, mucoadhesive polymers have gained increasing attention as key enablers in the development of advanced drug delivery systems for brain therapies. Among them, hyaluronic acid (HA) stands out for its exceptional tunability, biocompatibility, and processability, positioning it as a highly promising candidate for the treatment of central nervous systems (CNS) disorders across multiple administration routes (i.e. parenteral, intranasal, and oral). Areas covered: Current discoveries in material science and pharmaceutic formulations offer the chance to design HA-based transformative carriers for brain delivery and targeting, promoting a receptor-specific uptake and precise modulation of therapeutic responses within the CNS. Herein, recent advances in the design of HA-based platforms for brain drug delivery were critically examined with a particular focus on emerging strategies for HA synthesis, functionalization, and processing. By integrating advanced carrier design to innovative strategies of molecular targeting, HA-based systems can enhance brain accumulation, improve safety profiles, and unlock multimodal treatments. Expert opinion: HA-based platforms open new avenues to enhance drug targeting, therapeutic efficacy, and overall patient outcomes. Future challenge will be to overcome manufacturing, scalability, and translational barriers to translate this powerful platform from preclinical promise to clinical reality.