Abstract
BackgroundBrucellosis is a zoonotic disease caused by Brucella species. It has been estimated that more than 500,000 new cases of Brucellosis occur annually all around the world. Relapse of the disease is one of the most important challenges. The most important reason for the relapse of brucellosis is the survival of the bacteria inside the macrophages, which makes them safe from the immune system and disrupts drug delivery mechanism.ObjectivesThe present study was performed to assess the effects of Doxycycline-loaded Solid Lipid Nanoparticles (DOX-SLN) on the Brucella melitensis inside macrophages.MethodsDOX-SLN was prepared using double emulsion method. The technological characterization of DOX-SLN, including particle size, zeta potential, polydispersity index (PDI), drug loading and encapsulation efficiency were used. Fourier-transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC) were used to assess the interactions between Nanoparticles (NPs) components and crystalline form of doxycycline. Moreover, the effect of DOX-SLN on the bacteria were compared with that of the doxycycline using various methods, including well diffusion, Minimum Inhibitory Concentration (MIC), and investigation of their effects on murine macrophage-like cells cell line J774A.1.ResultsThe means of particle size, zeta potential, PDI, drug loading and encapsulation efficiency were 299 ± 34 nm, − 28.7 ± 3.2 mV, 0.29 ± 0.027, 11.2 ± 1.3%, and 94.9 ± 3.2%, respectively. The morphology of NPs were spherical with a smooth surface. No chemical reaction was occurred between the components. Doxycycline was located within NP matrix in its molecular form. The DOX-SLN significantly decreased the microbial loading within macrophages (3.5 Log) in comparison with the free doxycycline.ConclusionsSince the DOX-SLN showed better effects on B. melitensis enclosed in macrophages than the free doxycycline, it is recommended to use it for treating brucellosis and preventing relapse.
Highlights
Brucellosis is a zoonotic disease caused by Brucella species
Since the Doxycycline-loaded Solid Lipid Nanoparticles (DOX-Solid lipid nanoparticles (SLNs)) showed better effects on B. melitensis enclosed in macrophages than the free doxycycline, it is recommended to use it for treating brucellosis and preventing relapse
The results demonstrated that the rate of free doxycycline release was higher than that of DOX-SLN-1, suggesting that DOX-SLN-1 is capable to control the release of encapsulated doxycycline (P = 0.04)
Summary
Brucellosis is a zoonotic disease caused by Brucella species. Relapse of the disease is one of the most important challenges. The most important reason for the relapse of brucellosis is the survival of the bacteria inside the macrophages, which makes them safe from the immune system and disrupts drug delivery mechanism. Brucellosis is a zoonotic disease caused by different Brucella strains following direct or indirect contact of human with infected animals or dairy products [1]. The phagocytosis activity of polymorphonuclear and monomorphonuclear cells such as macrophages plays an important role in the disease treatment [3]. Some of them survive inside macrophages and find a place to proliferation within the cell [1, 4]
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