Thermoresponsive In Situ Gels for Intranasal Drug Delivery for Treatmentof Depression

Depression is a complex neuropsychiatric illness that requires prompt and efficient treatment. The conventional oral antidepressant treatments are frequently constrained by high first-pass metabolism and inadequate bioavailability, which delays the onset of effect, and thermoresponsive in situ gels have become a viable intranasal medication delivery method in recent years to address these issues. In order to achieve controlled drug release and sustained nasal residence, these systems take advantage of the special qualities of thermosensitive polymers, such as chitosan derivatives and poloxamers (Pluronic F127, F68), which undergo sol-gel transition at physiological temperatures. The olfactory and trigeminal nerves provide a direct nose-to-brain channel through intranasal delivery by avoiding the blood-brain barrier (BBB) and improving the bioavailability of the central nervous system. The current developments in the mechanism of nose-to-brain drug delivery for antidepressant delivery using different pathways of thermoresponsive in situ gels are consolidated in this study with design and formulation characteristics, mucoadhesive techniques, gelation mechanisms, and polymer selection are all emphasized. Along with recent advances in nanogel hybrids, stimuli-responsive systems, and customized intranasal therapies, issues with nasal mucosal irritation, formulation stability, and accessibility are also thoroughly examined. All things considered, thermoresponsive in situ gels offer an innovative and effective way to enhance the effectiveness of antidepressants, patient adherence, and treatment results for depression.