Application of Hyaluronic Acid in Enhancing the Efficacy and Safety of Paclitaxel Nanoformulations for Cancer Treatment: A Recent Review

Paclitaxel (PTX) has long been a cornerstone in cancer chemotherapy, yet its clinical use is limited by poor solubility and non-selective toxicity. Recent advances in nano drug delivery focus on improving water solubility and enhancing tumor specificity through ligand-receptor-mediated targeting. Among various ligands, hyaluronic acid (HA) has emerged as a promising candidate. HA is a natural glycosaminoglycan abundantly present in the extracellular matrix, with its receptor CD44 being highly overexpressed in many cancers, particularly in tumor-initiating cells. In this review, we discuss various strategies through which HA can enhance the therapeutic activity of PTX, including direct conjugation, self-assembly, cross-linked systems, and HA functionalization of both organic and inorganic nanoparticles. These approaches have demonstrated remarkable potential in improving PTX efficacy, safety, and tumor selectivity, and they hold great promises for future PTX-based cancer therapy.