Research Article Codelivery of Doxycycline and Hydroxychloroquine to Treatment of Brucellosis: An Animal Study Seyed Mostafa Hosseini , 1 Abbas Farmany, 2 Mohammad Yousef Alikhani, 1 Mohammad Taheri, 1 Sara Soleimani Asl, 3 Saeed Alamian, 4 Masoumeh Asgari, 5 and Mohammad Reza Arabestani 1,6 1 Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR, Iran 2 Dental Research Center, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, IR, Iran 3 Department of Anatomical Sciences, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR, Iran 4 Razi Vaccine & Serum Research Institute, Agricultural Research, Education & Extension Organization, Iran 5 Nutrition lab, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, IR, Iran 6 Brucellosis Research Center, School of Medicine, Hamadan University of Medical Sciences, Hamadan, IR, Iran Correspondence should be addressed to Mohammad Reza Arabestani; mohammad.arabestani@gmail.com Received 2 May 2022; Accepted 2 June 2022; Published 22 June 2022 Academic Editor: Ruibing Wang Copyright © 2022 Seyed Mostafa Hosseini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Evaluation of various biochemical and immunological parameters in infectious diseases is one of the best indicators for a diagnosis and treatment process. The main goal of this project is to determine the effect of hydroxychloroquine and doxycycline loading into solid-lipid-nanoparticles (DOX-HCQ-SLN) on the both acute and chronic phases of brucellosis. In addition, evaluate some biochemical factors, trace elements, and inflammatory elements. Blood serum levels of Zn, Fe, Na, and K and hepatic biochemical parameters (AST, ALT, ALP, and TBil) were remarkably different between infected and healthy rats. Vitamin D was decreased, and CRP was increased in chronic and acute brucellosis. Quantitative evaluation of these mentioned parameters can be useful to diagnose brucellosis in advance. Due to the good effect of the synchronized use of hydroxychloroquine and doxycycline in the form of nanoparticles, the manipulation of these nanoparticles can help for better treatment and also reduction in brucellosis reinfection. 1. Introduction Brucellosis is a zoonotic infection caused by four genus of Brucella, including B. melitensis, B. abortus, B. suis, and B. canis. The disease has nonspecific symptoms, multiple com- plications, and involvement of various organs [1, 2]. These intracellular pathogens, in the cell, can be safe in the extra- cellular conditions, and also the intracellular environment enables them to be resistant to extracellular antibiotics [3, 4]. As bacteria reside within macrophages and prevent apo- ptosis, the capability of bacteria to adapt the new conditions, bacterial growth in the macrophage cell, the inability of the host and treatment failure, and bacterial eradication are dif- ficult and therefore increase chronicity and disease recur- rence [5, 6]. Successful treatment depends on its duration and also the patient’s cooperation. Recurrences in the first six months of treatment happen milder than the early stages of the disease. Consequently, new methods are designed to decrease the chronic problems of infection [7, 8]. The most promising strategy is to use nanocarriers. Precise formula- tion of nanocarriers leads to higher stability and can speed up dissolution and their therapeutic effect and upgrade their bioavailability [9–11]. Trace elements are very important in biochemistry, nutrition, and enzyme structure [11]. So iden- tifying the exact role of these trace elements particularly in puberty, their function in activity and body defense can be a useful as well as helpful method in cell biology and genetics [11]. Trace elements have a critical role in the structure and Hindawi Journal of Nanomaterials Volume 2022, Article ID 4064925, 9 pages https://doi.org/10.1155/2022/4064925