Development and Characterization of In Situ Gelling Nasal Cilostazol Spanlastics

Abstract

Cilostazol (CIL), a BCS class II antiplatelet aggregation and vasodilator agent, is used for cerebrovascular diseases to minimize blood–brain barrier dysfunction, white matter-lesion formation, and motor deficits. The current work aimed to develop and optimize cilostazol-loaded spanlastics (CIL-SPA) for nose-to-brain delivery to overcome the low solubility and absorption, the first pass-metabolism, and the adverse effects. The optimal CIL-SPA formulation was loaded into Phytagel® (SPA-PG), Poloxamer-407 (SPA-P407), and chitosan (SPA-CS) gel bases and characterized in terms of colloidal properties, encapsulation efficiency (EE%), mucoadhesive properties, and biopharmaceutical aspects. The developed in situ gelling formulations showed a <300 nm average hydrodynamic diameter, <0.5 polydispersity index, and >|±30| mV zeta potential with a high EE% (>99%). All formulations met the droplet size-distribution criteria of nasal requirements (<200 µm), and all formulations showed adequate mucoadhesion properties. Both the BBB-PAMPA and horizontal permeability study through an artificial membrane revealed that all formulations had higher CIL flux and cumulative permeability at in vitro nose-to-brain conditions compared to the initial CIL. The in vitro drug-release study showed that all formulations released ca. 100% of CIL after 2 h. Therefore, the developed formulations could be promising for improving the low bioavailability of CIL through nose-to-brain delivery.