Chimerical agglomerates of lecithin/chitosan nanoparticles for powder nasal delivery

Purpose: To investigate the transformation of lecithin/chitosan nanoparticles in a powder weak agglomerated to be used for nasal drug administration. Methods: Lecithin/chitosan nanoparticles were produced by interaction of lecithin (Lipoid S45) with chitosan (low molecular weight, Fluka). Lecithin-chitosan nanoparticles have been characterized for their diameter, zeta potential, morphology and structural aspects (TEM, AFM and Micro-FTIR). The nanoparticles dispersed in a mannitol water solution have been transformed in microparticles by spray drying without modifying their original structure. Agglomerates were manufactured by tumbling 5 g of microparticle powder in a glass pan rotating at 50 rpm for 5 min. Microparticles’ and agglomerates’ morphologies have been analysed by SEM microscopy. The loading of nanoparticles with two model drugs (ketoprofene and metoclopramide) has also been performed. Results: Lecithin/chitosan nanoparticles of nearly 300 nm were obtained in a simple and reliable way. The surface charge of these nanoparticles resulted positive (+20 mV), as a function of amount of chitosan present on their surface. Encapsulation of lipophilic drug is favored by the experiment procedure with a loading efficiency greater than 40%. Nanoparticles were transformed in microparticles (5-8 μm) by spray drying their dispersion in mannitol solution and then in agglomerates. The agglomerates are defined chimerical since their size is temporary; in fact, the insufflation by means of nasal device (Monopowder® Valois S.A., France) produced small fragments suitable for nasal deposition and drug release. The chimerical agglomerates obtained by tumbling microparticles rapidly disgregated in presence of water, regenerating the original nanoparticle colloidal suspension. Conclusion: Lecithin-chitosan nanoparticles prepared showed a positive charge considered advantageous for the adhesion to nasal mucosa. The powder for nasal administration was obtained by agglomeration of microparticles. After insufflation, the agglomerates produced smaller fragments of microparticles, which gave back, upon disgregation in physiological fluids, the original nanoparticle system