Hyaluronic acid-navigated nanoplatforms for oral cancer management: Current advances, translational perspectives, and future outlook—A review

Oral cancer represents a significant global health burden exacerbated by aggressive tumor behavior and inadequate therapeutic outcomes, collectively contributing to high morbidity and mortality rates. Current treatment modalities, including surgery, radiotherapy, and chemotherapy, are often limited by a lack of tumor specificity, poor drug permeability, systemic cytotoxicity, and the emergence of multidrug resistance. Consequently, there is a growing demand for biomaterial-based systems to effectively target oral cancer. Among natural polysaccharides, hyaluronic acid (HA) has emerged as a highly promising biomaterial owing to its biocompatibility, biodegradability, and low antigenicity. Notably, HA exhibits a high affinity for the CD44 receptor, which is markedly overexpressed in oral squamous cell carcinoma (OSCC) and plays a key role in tumor progression, metastasis, and chemoresistance in oral cancer. This review highlights recent advances in HA-based delivery systems for oral cancer, focusing on physicochemical properties, biological interactions, and therapeutic efficacy. Various HA-based delivery systems such as nanoparticles, hydrogels, nanofibers, and microneedles have been explored for oral cancer management. Additionally, preclinical, translational, chemistry, manufacturing, and control (CMC), and regulatory considerations are discussed to highlight the clinical relevance of HA-based delivery platforms. Further, the current challenges and future perspectives of HA-based drug delivery systems have been elaborated.