| Autor: |
Sadozai, Sajid Khan, Khan, Saeed Ahmad, Karim, Nasiara, Becker, Dennis, Steinbrück, Nils, Gier, Stefanie, Baseer, Abdul, Breinig, Frank, Kickelbick, Guido, Schneider, Marc |
| Zdroj: |
Journal of Drug Delivery Science and Technology; April 2020, Vol. 56 Issue: 1 |
| Abstrakt: |
Ketoconazole is one of the most commonly used azole drug applied in the treatment of topical fungal infections. However, due to low aqueous solubility, Ketoconazole has limited bioavailability. Therefore a higher amount of drug is required to achieve the desired antifungal activity. Which can cause severe allergic and skin reactions. This study aims at designing Ketoconazole-loaded poly (lactide-co-glycolide) (PLGA) nanoparticles (<300 nm) that could potentially assemble in wrinkles and hair follicles to provide prolonged release to the skin tissue. Additionally, improvement of antifungal activity of Ketoconazole-loaded PLGA particles by concomitant use of silver nanoparticles was also tested. Emulsion/solvent evaporation method was used for the preparation of Ketoconazole-loaded PLGA nanoparticles. The particles were characterized using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (P-XRD), Differential Scanning Calorimetry (DSC), and Fourier-Transform Infrared Spectroscopy (FTIR). It was found that the size of nanoparticles increases with increasing drug/polymer ratio. Formulations with 12.5% Ketoconazole had the smallest particle size i.e., around 190 nm with a polydispersity index (PDI) of 0.19. Increasing drug/polymer ratio to 50% produced nanoparticles of 257 nm. Nanoparticles produced with 100% Ketoconazole without PLGA polymer had 271 nm size and a higher PDI of 0.301. The entrapment efficiency of all formulation was around 95%. DSC thermogram and P-XRD results demonstrated that at drug/polymer ratio <12.5%, Ketoconazole was entrapped as amorphous molecular dispersion in PLGA polymer. FTIR data showed the absence of any drug-polymer interaction. The in vitroantifungal activities of Ketoconazole and silver nanoparticles combination showed 5 - 30-fold reduction in MICs values compared to the sole application of one of the two particulate systems. Moreover, the studied combination had a Fractional Inhibitory Concentration Index value below 0.5 which indicates strong synergism. These findings suggest that the effect of Ketoconazole nanoparticles can be improved when concomitantly used with silver nanoparticles by increasing the susceptibilities against Candida albicans. |
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