Preparation and characterization of temperature sensitive chitosan/carboxymethyl cellulose/scleroglucan hydrogels with controlled drug release and antifungal property

In this study, temperature sensitive chitosan/carboxymethyl cellulose/ scleroglucan and chitosan/carboxymethyl cellulose/scleroglucan/montmorillonite hydrogels having liquid form at room temperature and turning into gel form on nail surface were prepared for use in the treatment of nail fungus. In order to improve mechanical and thermal properties and the swelling and release behaviors of hydrogels, montmorillonite clay (MMT) modified with phenyl alanine amino acid was used. Rheological measurements were carried out to determine the gelation temperature of hydrogels precisely and the optimum hydrogel system showing gelation at the external body temperature. Characterization tests of optimum hydrogel system with different MMT ratios were performed. Fourier transform infrared (FTIR), scanning electron microscope (SEM), energy dispersive X-ray (EDX), mapping, transmission electron microscope (TEM), thermal gavimetric analysis (TGA), differential scanning calorimeter (DSC), swelling tests, contact angle, opacity and mechanical strength analyses were carried out for characterization studies. TEM and XRD analyses showed the exfoliated distribution of MMT in the network structure of hydrogels. From TGA, the decomposition temperatures of hydrogel systems with %0, %1, %3 and %5 MMT were determined to be 145 °C, 158 °C, 165 °C and 175 °C, respectively. As a result of the DSC analysis, it was found that the glass transition temperature (Tg) values of the hydrogels rised with increasing amount of MMT in the hydrogel matrix. The thermal stability of hydrogels was increased by addition of the clay into the hydrogel matrix. When swelling behaviours of hydrogels in distilled water, acidic medium and basic medium were compared, it was found that maximum swelling was observed in acidic medium and minimum swelling was obtained in distilled water. Hydrogels reached to the equilibrium swelling degree in distilled water and basic medium and exhibited non-Fickian swelling behaviour. As the amount of clay in the hydrogel increased, a significant reduction in the swelling amount of hydrogel was detected. The contact angle value of the hydrogel system containing 0% MMT was 58.8°. On the other hand, the contact angle value of hydrogel enhanced to 77.9° when the clay content with in hydrogel matrix was rised to 5%. Hydrophilic character of hydrogel was declined by addition of clay. The addition of clay into hydrogel caused a decrease in %transmittance of the hydrogel and an augmentation in the opacity value. The compressive stress values obtained from mechanical compression test were 126.45±8.83 kPa for clay free system, 266.99±6.60 kPa for system containing the highest amount of clay. Also, antifungal drug release and antifungal activity studies were performed. Antifungal oxiconazole nitrate (OXI) drug was loaded to hydrogel and its release was monitored spectrophotometrically. OXI release amounts at the end of 420 minutes were determined as 70.33±1.74%, 63.92±0.31%, 58.78±1.45% and 52.89±0.21% for hydrogel systems containing 0%, 1%, 3% and 5% MMT, respectively. Hence, it was seen that drug release can be controlled by changing the amount of clay in hydrogel matrix. Antifungal activities of OXI loaded hydrogels were investigated against Trichophyton mentagrophytes dermatophyte and hydrogels showed high antifungal activity.