Augmenting the safety and therapeutic efficacy of doxycycline and rifampicin-loaded solid lipid nanoparticles against Brucella abortus using murine model

Abstract

Background

Prolonged therapy, hepatic damage, and the development of drug resistance are the limitations of doxycycline and rifampicin in the treatment of brucellosis. This study was designed to assess the effect of solid lipid nanoparticles (SLNs) encapsulation of these antimicrobials against brucella. SLNs were prepared by a double emulsion method and characterized for entrapment efficiency, particle size distribution, drug release, infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The encapsulated formulations were tested for stability, safety, and in vitro antimicrobial assay on brucella and brucella-infected mice models.

Results

The particle size, polydispersity index and zeta potential of doxycycline encapsulated SLN size were 443.6 ± 3.03 nm, 0.858 ± 0.00, and + 26.5 ± 1.87 mV, respectively. The rifampicin SLN showed particle size, polydispersity index, and zeta potential of 348.7 ± 3.35 nm, 0.234 ± 0.00, and + 22.9 ± 1.59 mV. The entrapment efficiency of doxycycline and rifampicin encapsulated SLN was 98% and 96%, respectively. The drug-loaded SLN retained the biophysical properties, drug loading, and entrapment efficiency after storage at 4 °C as well as 25 °C for 6 months. The Fourier transform infrared spectroscopy depicted effective encapsulation and the Differential scanning colorimetry thermogram revealed a negative interaction of drug and polymer. Drug release parameters were fitted well with the Korsmeyer–Peppas and Hixson–Crowell model (R2 ≥ .09). The MIC findings showed a reduction in MIC values of SLN-encapsulated rifampicin; whereas, doxycycline did not show any changes. The MBC value for free and SLN-encapsulated doxycycline and rifampicin did not show changes. SLN encapsulation did not show any cytotoxicity on murine macrophage cell line RAW 264.76 for both drugs. Doxycycline and rifampicin significantly reduced the CFU of B. abortus compared to the free drug (P > 0.05), resulting in less damage to the liver and kidneys.

Conclusions

The present study concludes that SLN encapsulation of doxycycline and rifampicin would be safe and effective for the prolonged treatment regimen against Brucella infection.

Graphical abstract