Nano-drug delivery systems for the treatment of brucellosis: current evidence, translational lessons from tuberculosis nanotherapy, and future directions

Background Brucellosis, caused by facultative intracellular bacteria, evades host immunity and resists conventional antibiotics, frequently progressing to chronic infection and posing substantial clinical challenges. Objective This review aims to comprehensively summarize recent advances in nanocarrier-based drug delivery systems for the treatment of intracellular bacterial infections, using Brucella as a representative pathogen, and to explore their potential for future clinical application. Methods We systematically reviewed the design strategies, characteristics, and anti-Brucella efficacy of various nano-drug delivery systems loaded with antibiotics such as doxycycline and rifampicin. In addition, we evaluated combination therapy approaches, including stimulus-responsive drug release and photothermal therapy. Results Nanocarriers elevate intracellular drug deposition, extend therapeutic retention time and mitigate systemic side effects, thereby yielding markedly better antibacterial performance than unencapsulated antibiotics. Combined therapeutic regimens can further boost anti-Brucella potency. Conclusion Nano-drug delivery platforms hold great promise for the clinical management of intracellular pathogens exemplified by Brucella spp. Future research should prioritize long-term biosafety assessment, scalable manufacturing processes, and clinical translation.