Journal of International Research in Medical and Pharmaceutical Sciences

Intranasal administration has re-emerged as a pharmaceutically attractive non-invasive route for systemic and central nervous system drug delivery, owing to the high vascularity and permeability of the nasal mucosa and its capacity to circumvent hepatic first-pass metabolism. Among the carrier technologies developed to overcome the principal limitations of this route, namely rapid mucociliary clearance and restricted membrane permeability, spanlastic nanovesicles have attracted sustained interest because their deformable bilayer, conferred by an edge activator, allows efficient accommodation within the narrow intercellular spaces of the nasal epithelium. When such vesicles are dispersed within a stimuli-responsive in situ gelling matrix, the resulting nanospanlastic in situ gel combines nanoscale carrier flexibility with prolonged mucosal residence, addressing two of the most persistent formulation bottlenecks simultaneously. This review synthesises the pharmaceutical rationale, formulation composition, preparation methodologies, optimisation strategies and preclinical evidence base for nasal in situ nanospanlastic gels intended for systemic and brain-targeted delivery. Particular attention is given to the physicochemical interplay between spanlastic vesicle characteristics and gelling polymer selection, to the design-of-experiments approaches used to optimise such multicomponent systems, and to the biopharmaceutical, safety and regulatory considerations that will determine their translational trajectory. The available preclinical data, spanning drugs as diverse as cilostazol, carbamazepine, rasagiline, flibanserin, piperine, lamotrigine and granisetron, consistently demonstrate improved nasal residence, enhanced permeability and superior central or systemic bioavailability relative to conventional nasal solutions. Nonetheless, the field remains almost entirely preclinical, and questions of manufacturing scalability, long-term physical stability, and human translational relevance are only beginning to be addressed. The review closes by identifying priority research directions and articulating the principal limitations of the current evidence base.