Brucella is a facultative intracellular coccobacilli, spore-free, capsule-free and nonmotile gram-negative bacillus of various types and, at least, four of them are pathogenic in humans, including Brucella melitensis, Brucella abortus, Brucella suis and Brucella canis .
Because of the high ability of Brucella bacteria to survive and hide within cells after treatment, relapse of brucellosis will occur after a few months due to a weakened immune system . Most relapse occur within the first six months after treatment with clinical findings milder than the initial course of the disease, although some patients, in particular, show mild clinical relapse . It should be noted that the mechanism of host immune response to brucellosis may be varied, depending on the host and strains of Brucella. The goal of any treatment for brucellosis in humans is to fight the symptoms, reduce the complications and ultimately prevent its relapse. Since, it is difficult to completely eradicate the microorganism, antibiotic compounds are prescribed to produce a long-term synergistic effect [3,4].
Low stability in the intracellular environment or degradation by lysosomal enzymes results in the inefficiency of antibiotics administered against intracellular microorganisms. However, the wide distribution of these drugs does not reach the organism fully and its presence in non-infectious tissues apart from their intrinsic toxicity may lead to adverse effects .
Despite the emergence of a significant number of new antibiotics, the treatment of intracellular pathogens still represents a challenge in pharmacy . Nowadays, with the preparation of pharmaceutical nanoparticles, unique properties can be achieved that will increase the performance and variety of its drug forms. Accurate formulation of nanoparticles results in their higher stability and can increase the rate of dissolution and reaches biological levels, which will accelerate their therapeutic effect and improve their bioavailability [7,8].
At this time, the need to develop drug delivery systems that can overcome these problems seems very urgent. These carrier systems should be non-toxic, capable of accepting sufficient amounts of drug, and in addition capable of targeting and controlling drug release . Solid lipid nanoparticles as a carrier system have been investigated for many applications. Many drugs have been successfully incorporated into the SLN with a variety of uses. These drug delivery systems controls the release of drugs and increase the chemical stability of drugs[10,11].
Regardless of the role of vitamin D in calcium homeostasis, it has an essential role in the innate and acquired immune system. This effect is exerted by vitamin D receptors on many immune cells [12,13]. This vitamin has the role of regulating the level of immunity and serum levels of this micronutrient affect the susceptibility and outcome of many infections. There is ample laboratory evidence of a correlation between serum vitamin D levels and the risk of infectious diseases. Vitamin D has been shown to increase phagocytosis of macrophages and increase the production of cathelicidin antimicrobial peptide and accelerate killing of intracellular bacteria. On the other hand, the INF1-dependent antimicrobial pathway in human macrophages is associated with appropriate serum levels of vitamin D [14,15].
Due to the fact that brucellosis affects the vital organs of the body, including the liver, spleen, joints, etc., their function is impaired and increases or decreases various enzymes and proteins in the body. In some studies, using electrophoresis of proteins in the serum, serum levels of proteins change during infectious diseases that are associated with long-term inflammation. C-reactive proteins are acute phase reactants. In 99% of healthy adults, the concentration of CRP in the serum is less than 1 mg/L. The rapid increase in CRP is observed in most infectious diseases.
The aim of this study was to evaluate the therapeutic effect of doxycycline-loaded solid lipid nanoparticles (SLN) on acute and chronic brucellosis and its effect on serum levels of vitamin D, CRP and proteins in in vivo condition.