Mucoadhesive itraconazole nanocrystals with precise control of surface charge incorporated to chitosan films for buccal drug delivery

Drug delivery to mucosal tissues presents considerable challenges related to the complex nature of the mucus layer protecting such tissues. This aggravates when delivering hydrophobic drugs, often requiring incorporation of drugs to nanoparticles and use of mucoadhesive systems. This paper aimed to develop an antifungal chitosan (CHI)-based film loading itraconazole (ITZ) nanocrystals (NCs) with precisely controlled surface charge for enhanced mucoadhesion. Cationic and anionic ITZ NCs are prepared using wet media milling with mean particle sizes and zeta potentials of 226.9 ± 1.4 nm and 234.0 ± 2.90 nm, and +15.4 ± 2.8 mV and −16.2 ± 1.3 mV, for the cationic and anionic NCs, respectively. Cationic ITZ-NCs exhibits a higher affinity to mucin particles. NCs-loaded films showed stronger mechanical properties and adhesiveness compared with ITZ powder-loaded films. Physicochemical analysis reveals that crystalline properties of the ITZ are preserved, with no drug-excipients interaction. A significantly higher amount of ITZ mucosal deposition is obtained from films containing NCs (1360.23 ± 718.73 µg cm⁻²) compared with that from films containing ITZ powder (58.83 ± 37.45 µg cm⁻²). This work demonstrates the feasibility of tailoring the NCs surface, with the resultant systems showing potential for the management of fungal infections in mucosal tissues.