When one wants to target a specific infection within a particular organ of the body, often systemic antimicrobial drugs are required. This can lead to unwanted side effects in other parts of the body and amplify the risk of bacterial resistance. Biomedical research undertaken at the University of California in San Diego investigated a microrobot containing nanoparticle-modified algae to actively deliver therapy to lung disease [Zhang, F.; Zhuang, J.; Li, Z.; Gong, H.; et al. Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia. Nature Materials Nov 2022, vol 21, pp. 1324-1332; doi:10.1038/s41563-022-01360-9].
The study examined the potential use of this drug delivery vehicle for ventilator-associated pneumonia (VAP) in human hospital patients; such an infection is potentially fatal. The biohybrid robot in the study contains Chlamydomonas reinhardtii microalgae combined with nanoparticles loaded with ciprofloxacin that targets lung infection with Pseudomonas aeruginosa. The neutrophil membrane coating helps the microrobot evade immune clearance by the body so it can reach its target for drug delivery.
Via intratracheal administration, the algae-nanoparticle robot was introduced into mice infected with P. aeruginosa. Using their flagella, the modified algae were able to move through the lungs and achieve uniform dispersion within an hour. It was then retained and active for at least 24 hours.
Over the 14-day study, 100% of the mice treated this way survived. In contrast, untreated mice died within three days. The authors report that “prolonged lung retention and sustained release characteristics of an algae-nanoparticle-ciprofloxacin-robot enabled significant improvement in survival compared with control groups.” Treatment with the microrobot also outperformed intravenous treatment with ciprofloxacin at the same dose in one trial and further achieved efficacy at a ciprofloxacin dose 3,000 times smaller than that given intravenously.
Safety factors were evaluated, with favorable findings—the microrobot did not trigger production of proinflammatory cytokines or other signs of inflammation.
Besides using this kind of biomedical technology for human conditions in future, researchers are also investigating implementing this therapy into inhalers containing live organisms. While the microrobot approach has not been tried in humans, this discovery holds promise and might eventually become an option for targeted veterinary therapeutics.
