Rosmarinic acid based nasal spray formulation. Comparative study of nanoemulsions vs solid lipid nanoparticles

Despite the recognized therapeutic potential of Rosmarinic Acid (RA), its clinical use remains limited due to poor water solubility, chemical instability, and rapid mucociliary clearance following intranasal administration. To address these limitations, two different nanocarriers: Solid Lipid Nanoparticles (SLNs) and oil-in-water nanoemulsions (O/W NEs) were designed, prepared and characterized, to improve the intranasal delivery and therapeutic efficacy of RA in allergic rhinitis. These nanosystems were optimized to encapsulate RA, enhancing its solubility and enabling controlled release. To prolong residence time at the nasal mucosa, chitosan was introduced in RA-based NEs as mucoadhesive polymer. A comprehensive physicochemical characterization was carried out, including evaluation of size, zeta potential, membrane fluidity, and structural organization. Stability was assessed under storage and physiologically conditions. In particular, Atomic Force Microscopy (AFM) and Small-Angle X-ray Scattering (SAXS) analyses were conducted to gain deeper insights into the formulations surface morphology and internal nanostructure. Obtained results confirmed the ability of both systems to protect RA from degradation and promote sustained release. Mucoadhesion studies demonstrated the interaction of the chitosan-coated NEs with mucin, increasing retention on the nasal mucosa. Among the two formulations, SLN-RA was selected for nasal spray development and extensively characterized, including resistance to nebulization, droplet size distribution, and microbiological and pharmacological studies, to evaluate its suitability for intranasal administration. The results confirmed that the SLN-based nasal spray maintained favorable physicochemical and mucoadhesive properties, ensuring efficient delivery to the upper respiratory tract. Biological assays revealed that encapsulated RA retained its antioxidant and anti-inflammatory properties, reducing the expression of inflammatory markers such as High Mobility Group Box 1 (HMGB1). Altogether, these findings suggest that SLNs represent the best and promising carrier for the non-invasive delivery of RA in the nasal cavity. Their integration into nasal spray formulations could offer an effective therapeutic strategy for allergic rhinitis and other inflammatory conditions of the upper respiratory tract.