Clotrimazole nanosuspensions-loaded hyaluronic acid-catechol/polyvinyl alcohol mucoadhesive films for oral candidiasis treatment

This work aimed to develop oral mucoadhesive films containing clotrimazole (CZ) nanosuspension (NSP) for oral candidiasis treatment. Various CZ-NSP were formulated using different stabilizers (Tween 80 and chitosan derivatives). The physicochemical properties and the CZ content of the NSP were assessed. The NSP were mixed with a polymer mixture of catechol-functionalized hyaluronic acid (HA-cat)/polyvinyl alcohol (PVA) to prepare the mucoadhesive film using film-casting method. The physicochemical, mechanical and mucoadhesive properties of the film were evaluated. Moreover, the drug content, release characteristics together with the cytotoxicity and antifungal activity were investigated. The optimal CZ to stabilizer ratio was 2.5:1. CZ-Benzyl-succinyl chitosan NSP (BSCS-NSP) provided the highest CZ concentration. X-ray diffractogram revealed an amorphous state of the CZ-BSCS-NSP. The presence of the CZ-BSCS-NSP in the film was confirmed by FT-IR and scanning electron microscope (SEM). The HA-cat/PVA films exhibited better mucoadhesion compared to the unmodified HA/PVA films. The gradual release of CZ from the CZ-BSCS-NSP loaded film was observed, and the complete release was obtained at 6 h. The CZ-BSCS-NSP loaded films were safe to the normal cells and exhibited greater antifungal effect compared to CZ suspension. Therefore, the CZ-BSCS-NSP incorporated mucoadhesive film may be a candidate for oral candidiasis treatment.