Abstract
<jats:p>The blood-brain barrier (BBB) represents a major obstacle in the therapeutic management of disorders related to the central nervous system (CNS), blocking the access of almost 98% of small molecule medications and practically all large molecules. Intranasal drug administration represents a viable alternative to overcome the BBB, based on its ability to deliver directly from the nasal cavities into the brain using the routes of olfactory and trigeminal nerves, offering a direct nose-to-brain drug delivery pathway. Despite its advantages, intranasal drug delivery remains constrained by factors such as quick clearance, short retention and poor permeation of the drugs through biological membranes, to address these challenges, the in-situ gelling systems containing mucoadhesive polymers have been developed. Nasal in-situ transferosomal gels offer a novel formulation technique that incorporates the benefits of both transferosomal vesicular drug delivery systems and stimuli-responsive gel matrices for brain targeting. Keywords: Transferosomes, in-situ gel, Intranasal, Nose-to-brain, Blood-brain barrier, Vesicular drug delivery, Mucoadhesive systems, Brain targeting.</jats:p>