The simultaneous carrier ability of natural antioxidant of astaxanthin and chemotherapeutic drug of 5-fluorouracil by whey protein of ß-lactoglobulin: spectroscopic and molecular docking study.

In the present study, the simultaneous carrier ability of natural antioxidant of astaxanthin (ATX) and chemotherapeutic drug of 5-fluorouracil (5-FU) by whey protein of ß-lactoglobulin (ß-LG) using various spectroscopic techniques (UV-visible, fluorescence, circular dichroism (CD) and dynamic light scattering) in combination with molecular docking were investigated (at room and physiological temperatures). According to the fluorescence quenching tests, the binding parameters between drug and ATX with protein showed that the number of their binding sites was the same in the single and competitive states. Molecular docking results have showed completely consistent with the fluorescence data that presented the independent binding sites for 5-FU and ATX on ß-LG. Also, analysis of Far-UV-CD showed that the simultaneous binding of the drugs to the protein partially enhances its stability, which is associated with the decreasing in ß-sheet structure and increasing in α-helix. According to the Zeta potential measurements in the presence of different concentrations of the drugs, they have stronger binding to the protein at lower concentrations. Therefore, given the remarkable features of ß-LG, including the ability to interact simultaneously with the natural compound of ATX and the antitumor drug of 5-FU, this study could provide useful information for the development and improvement of new protein carrier systems with synergism potency. Communicated by Ramaswamy H. Sarma.

Doxycycline-encapsulated solid lipid nanoparticles for the enhanced antibacterial potential to treat the chronic brucellosis and preventing its relapse: in vivo study.

BACKGROUND: Brucellosis is one of the most important infection of diseases. Due to its large period of treatment and survival ability of bacteria inside the macrophages, relapse of this disease is the main challenge, especially, after the treatment. OBJECTIVE: The current study was carried out to evaluate the antibacterial effect of solid lipid nanoparticles loaded with doxycycline on the Brucella melitensis in in vivo conditions. METHODS: The double emulsion synthesized doxycycline-encapsulated solid lipid nanoparticles (DOX-SLN) was characterized using DLS and FE-SEM. The efficacy of the DOX-SLN on the acute and chronic Wistar rat infected brucellosis was investigated. The pathological assessments were made on the spleen and liver in the treated rates. RESULTS: The in vivo experimental results demonstrated that the treated rats with DOX-SLN had significantly decreased the B. melitensis CFUs in their spleen and liver compared to that of the treated rates with free doxycycline and untreated ones. The pathologic results indicate that the improvement trend of spleen and liver tissues in rats treated by DOX-SLN was satisfactory. CONCLUSION: According to in vivo results, the DOX-SLN has better effects on the treatment of chronic brucellosis. Therefore, DOX-SLN is recommended to treat the brucellosis and avoid its relapse.

Doxycycline-encapsulated solid lipid nanoparticles as promising tool against Brucella melitensis enclosed in macrophage: a pharmacodynamics study on J774A.1 cell line.

Background: Brucellosis 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. Objectives: The present study was performed to assess the effects of Doxycycline-loaded Solid Lipid Nanoparticles (DOX-SLN) on the Brucella melitensis inside macrophages. Methods: DOX-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. Results: The 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. Conclusions: Since 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.