Hyaluronic Acid Nanofiber Platform for Mucosal and Skin Drug Delivery: Recent Advancements and Translational Outlook

The nanofibers based on hyaluronic acid (HA) have been considered as the promising platform in the mucosal and skin delivery of drugs due to its distinctive physicochemical, biological, and biomimetic characteristics. HA is a naturally occurring glycosaminoglycan which is biocompatible, biodegradable, mucoadhesive and has high hydration capacity and is ideally suited to local therapeutic delivery through the epithelial barriers. HA nanofibers electrospun have a high surface area, tunable porosity, and the potential to deliver a wide range of therapeutic molecules, including small molecules, biologics, probiotics, and growth factors, which allows them to release drugs in a controlled and targeted manner. Their recent progress is shown to be effective in the treatment of the mucosal diseases like oral ulcers, vaginal infections, sinusitis, and mucositis and dermatological diseases like wounds, inflammatory skin diseases, and systemic therapy through the transdermal route. The mechanical strength, drug loading and stabilization of HA and carrier polymers, chemical modifications and multifunctional nanocomposites have been enhanced, solving the inherent processing issues with HA electrospinning. However, toxicity of HA can change depending on the molecular weight, modifications and formulation ingredients. Clinical translation is still dependent on thorough toxicological evaluation and regulatory compliance. Translational barriers, such as mass-manufacturing, prolonged safety testing, regulatory issues, and clinical validation, still continue to pose a challenge despite promising preclinical results. This review summarizes the recent advancements in the field of HA nanofiber fabrication, physicochemical optimization, therapeutic use as well as translational perspective with particular focus on their future as the next-generation platforms to deliver drugs to the mucosal and skin.