Use of the quantum dot-labeled solid lipid nanoparticles for delivery of streptomycin and hydroxychloroquine: A new therapeutic approach for treatment of intracellular Brucella abortus infection

Abstract

Brucellosis is considered one of the most important infectious diseases affecting any tissue and organ in the human body. Due to the intracellular pathogenesis of Brucella species, the use of conventional antibiotics for managing chronic brucellosis has several limitations. Therefore, the study focused on the use of solid lipid nanoparticles (SLN) to deliver streptomycin (STR) for intracellular infection, with or without the combination of hydroxychloroquine (HCQ) to evaluate if there might be a boost in the antibiotic effect when using the STR or STR-NPs alone. We used the double emulsion technique to synthesize Nano drug carriers; afterward, the physicochemical characteristics of synthesized Nano drug carriers were determined. The in vitro antibacterial activity of free drugs and Nano drug carriers were evaluated using well diffusion, broth microdilution assays (BMD), and murine macrophage-like cells cell line J774A.1. Additionally, acute and chronic phases of brucellosis were inducted into Wistar rats, and healing capacity of Nano drug carriers on liver and spleen tissues was compared with free drugs. The zeta potential of nanoparticles, means of size, Polydispersity Index (PDI), drugs loading, and encapsulation efficiency were 15.2 mV, 312.5 ± 26 nm, 0.433 ± 0.09, 16.6% and 89.5%, respectively. Well diffusion and BMD methods did not show a significantly differ between free drugs and nano drug carriers. However, the Nano drug carriers remarkably decreased the number of bacteria in the cell line compared to the free drugs. STR/HCQ-SLN enhanced the healing processes of the liver and spleen after brucellosis induction. STR/HCQ-SLN showed better inhibitory effects against the chronic phase of B. abortus infection in comparison to the STR-SLN, but this difference was not statistically significant. Using nanoplatforms to enhance conventional anti-brucellosis agents is promising, green and safe. Due to the continuous release of drugs, drugs increase their accumulation at the site of infection, causing a more significant effect on the chronic and acute phases of brucellosis.