MIKROBIYOLOJI BULTENI, cilt.59, sa.2, ss.228-241, 2025 (SCI-Expanded, Scopus, TRDizin)
Leishmaniasis is an important tropical disease affecting approximately 12-15 million people in countries where preventive measures such as hygiene, infrastructure and vector control are insufficient. Despite intensive research, a fully effective prevention and treatment strategy for leishmaniasis has yet to be established. Due to the side effects of antiparasitic drugs and their potential to cause severe complications, there is a need to discover and develop appropriate treatment methods or identify potent antileishmanial compounds. This study aimed to evaluate the cytotoxic activity, antileishmanial efficacy and synergistic potential of hybrid nanoparticles (NPs) synthesized using volatile oil components namely cinnamaldehyde (Cin), carvacrol (Car) and thymol (Tim) combined with silver nanoparticles, in conjunction with standard antileishmanial drugs. Amylose was preferred as the reducing agent during the synthesis of silver (Ag) as a NP. As a result of the synthesis, three different hybrid nanoparticles were synthesized, namely Cin Ag (OA-CinAgNP), Car Ag (OA-CarAgNP) and Tim Ag (OA-TimAgNP), which have oxidized amylose at the core. The synthesized NPs were characterized using FT-IR spectroscopy, as well as transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses. The cytotoxicity of the NPs was determined on L929 fibroblasts and their antileishmanial activity was assessed against the Leishmania tropica (MHOM/AZ/1974/SAF-K27) strain using the broth microdilution method. The interactions of NP complexes with the antileishmanial drugs pentostam and miltefosine were determined using the checkerboard method. Characterization analyses show that the amylose surface was successfully coated with Ag, Cin, Car and Tim and the resulting hybrid complexes were successfully synthesized. SEM analyses of the hybrid NP complexes revealed that the Ag ions and essential oil components were deposited on the surfaces of oxidized amylose at the core of the structure, confirming the successful synthesis of the NP complexes. The obtained images showed that the morphological shapes of the NPs varied from round to irregularly edged structures. TEM analysis indicated that the NP sizes were varied from 9.34 to 14.45 nm for OA-CinAgNP, 9.88 to 32.3 nm for OA-CarAgNP and 12.01 to 20.01 nm for OA-TimAgNP. The cytotoxic activities of OA-CinAgNP, OA-CarAgNP and OA-TimAgNP hybrid NP complexes against fibroblast cells at 24, 48 and 72 hours were observed to be in the ranges of 209.6-169.5 pg/mL, 190.4172.3 pg/mL, and 286.4-259.8 pg/mL, respectively. Antileishmanial activities of NPs were observed to be in the ranges of 66.04-53.87 pg/mL, 54.44-47.01 pg/mL, and 78.14-58.33 pg/mL, respectively. It was found that the NPs exhibited high antileishmanial activity with a selectivity index of > 3. Synergistic interactions were observed in all successfully synthesized hybrid NP complexes when combined with pentostam and miltefosine. Investigation of new bioactive compounds with lower toxicity compared to traditional drugs has become essential in the treatment of leishmaniasis. In this context, the development of natural products with pharmacological potential through nanotechnology applications could provide significant contributions to treatment strategies. The hybridization of effective essential oil components, such as Cin, Car and Tim, with Ag NPs and the demonstration of their strong antileishmanial activities, along with their synergistic interactions with existing antileishmanial drugs, may fill important gaps in the literature. This approach could guide future studies for designing new drug combinations, reducing side effects and preventing the development of resistance.