Detection of Candida spp. from mastitis cattle milk and study of the antifungal activity of ketoconazole-loaded solid lipid nanoparticles and nanostructured lipid carriers against Candida isolates

Objective: To isolate candida species from cattle milk isolates and investigate the advances of ketoconazole-loadedsolid lipid nanoparticles and ketoconazole-nanostructured lipid carters, and to analyse their properties and comparetheir antifungal performance compared to free ketoconazole.Method: The cross-sectional study was conducted from October 2021 to April 2022 in Waist Governorate of Iraq, andcomprised milk samples obtained from cows infected with mastitis. The study was initiated after obtaining approvalfrom the IRB of the veterinary hospital in the Governorate of Iraq. The samples were cultured on 4% savoured dextroseagar and incubated independently at 37°C before they were subjected to a range of tests. Mastitis was checked witha commercially available cultural and morphological identity card system and through candida chromogenic agar.The data was analyzed by using the programmed SPSS IBM version 20. The chi-square test was used to check theinhibition zones due to the anti-fungal activity of KTZ-LPN and free KTZ. The significance level was kept at p<0.05.Results:Of the 225 samples, 116(51.5%) were obtained from cows infected with mastitis on the basis of a commerciallyavailable cultural and morphological identity card system. Among the 61(52.6%) candida albicans isolated, resistanceto amphotericin B was shown by 60(98%) and to nystatin by 58(95%), while those sensitive to ketoconazole were32(52%) and to fluconazole 31(51%).The ketoconazole nanostructured lipid nanoparticle (KTZ-NLC) preparationsshowed higher antifungal activity than other tested preparations at 0.25ug/ml with a minimum inhibition zone of15±2.4 mm followed by ketoconazole solid lipid nanoparticle (KTZ-SLN) preparations with minimum inhibition zoneof 15±1.3 mm. Free ketoconazole showed the lowest inhibition zone values at the same concentration (0.25ug/ml),which was 11±1.3 mm. Both these lipid nanoparticles formulations, especially ketoconazole nanostructured lipidcarriers (KTZ-NLC), could represent a promising formulation for antifungal application and use.Conclusions: Ketoconazole-nanostructured lipid carter formulations were found to be effective for drug delivery.Keywords: Nanoparticles, Fluconazole, Amphotericin, Ketoconazole, Nystatin, Drug, Milk, Candida, Mastitis.