Hydrogel-Based Intranasal Delivery System for Neurotherapeutics: A Review

The effective delivery of therapeutic agents to the central nervous system (CNS) remains a major challenge because of the blood–brain barrier (BBB), which restricts the penetration of many drugs into brain tissue. Intranasal drug delivery has emerged as a promising, non-invasive approach for brain targeting because drugs administered through the nasal cavity may reach the brain through olfactory and trigeminal pathways while reducing dependence on systemic circulation. However, rapid mucociliary clearance, limited nasal residence time, enzymatic degradation and restricted absorption can reduce the efficiency of conventional nasal formulations. Hydrogel-based intranasal delivery systems have therefore received increasing attention. Hydrogels can provide mucoadhesion, prolonged nasal residence, controlled drug release and improved protection of therapeutic molecules. In particular, thermosensitive and mucoadhesive hydrogels prepared using polymers such as chitosan, poloxamer 407, poloxamer 188, carbopol, alginate and hyaluronic acid have been investigated for nose-to-brain delivery. Chitosan is especially attractive because of its biocompatibility, biodegradability, mucoadhesive properties and ability to enhance epithelial permeation. Recent studies have also combined hydrogels with nanoparticles, lipid carriers and other nanocarriers to improve drug stability, retention and brain delivery. This review discusses the principles, advantages, polymers, preparation methods, evaluation parameters, therapeutic applications, limitations and future prospects of hydrogel-based intranasal systems for neurotherapeutics.