Use of doxycycline-encapsulated Solid Lipid Nanoparticles as a New Strategy to Treat chronic rucellosis and prevent its Relapse: a Pharmacodynamics Study on Wistar Rats

Background and Objectives: Major challenge of brucellosis is related to its relapse which can be due to the bacteria survival inside the macrophages that keeps them safe from the host immune system and subsequently drug delivery mechanism interruption. The present study was carried out to evaluate the effects of Doxycycline-loaded Solid Lipid Nanoparticles (DOX-SLN) on the Brucella melitensis in in vitro and in vivo conditions. Materials and Methods: The double emulsion method was used to prepare DOX-SLN. The DOX-SLN features like particle size, polydispersity index (PDI), drug loading, zeta potential and encapsulation efficiency were assessed. To evaluate the interactions between NPs (NPs) components and crystalline form of doxycycline, Fourier-transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC) were applied. The efficacy of the formulations developed was investigated in both in vitro and in vivo conditions. Results: The results indicated that the average size of particle, PDI, zeta potential, drug loading and encapsulation efficiency were 299±34 nm, 0.29±0.027, -28.7±3.2 mV, 11.2±1.3%, and 94.9±3.2%, respectively. NPs have a smooth surface with spherical morphology. Doxycycline was placed in molecular form within NP matrix while no chemical reaction occurred between the components. Compared to the free doxycycline, DOX-SLN could significantly decrease the microbial loading in macrophages (3.5 Log) without any cytotoxic effects. The in vivo experiment demonstrated that rats treated with DOX-SLN had a significantly lower number of CFUs in their spleen and liver, compared to those of untreated rats. According to the pathologic results, the improvement trend of spleen and liver tissues in rats treated by DOX-SLN was satisfactory. Conclusion: According to in vitro and in vivo results, the DOX-SLN indicated better effects on B. melitensis attached in macrophages than free doxycycline, therefore, using NPs to treat brucellosis and avoid its recurrence is recommended.