A Review on Self-Nanoemulsifying Drug Delivery Systems for Intranasal Administration

Review Article

Abstract

Poor aqueous solubility and extensive presystemic metabolism restrict the systemic availability and central nervous system accumulation of lipophilic therapeutics classified under the Biopharmaceutical Classification System as Class II and IV entities. Intranasal administration helps in bypassing the hepatic clearance while providing an anatomical route directly into the central nervous system via the olfactory and trigeminal neuronal routes. Self-nanoemulsifying drug delivery systems are isotropic blends of non-ionic surfactants, lipophilic cosurfactants, and structured glyceride oils that spontaneously generate oil-in-water nanoglobules upon contact with endogenous fluids. This can achieve sub-100-nanometer dispersion, protects labile active molecules from mucosal peptidases and cytochrome P450 isoenzymes, and modulates tight junction integrity across the respiratory and olfactory neuroepithelium. Physicochemical optimization depends on thermodynamic boundary mapping via pseudo-ternary phase equilibria and statistical response surface methodologies to evaluate globule diameter, polydispersity, zeta potential, and emulsification kinetics. The use of functional mucoadhesive polymers counteracts rapid nasal mucociliary clearance, prolonging retention against the mucosal epithelial lining. Evaluation of these systems include ex vivo transmucosal permeation kinetics across excised tissues, assessments of ciliotoxicity, and pharmacokinetic compartmental modeling of cerebrospinal fluid and brain parenchyma. Self-nanoemulsifying systems provide a non-invasive therapeutic conduit for managing neurodegenerative, psychiatric, and acute neurovascular conditions