Antibiotic-Loaded Smart Platelet: A Highly Effective Invisible Mode of Killing Both Antibiotic-Sensitive and -Resistant Bacteria

[Image: see text] Microbial pathogenesis is considered one of the most critical health challenges worldwide. Although several antibiotics have been procured and used, the microbes often manage to escape and become resistant to antibiotics. Thus, the discovery of new antibiotics and designing smart approaches toward their delivery are of great importance. In many cases, the delivery agents using foreign chemicals like lipids or polymers induce immunogenic responses of varying degrees and are limited to a shorter circulatory time and burst release. In the current work, we have designed a novel antibiotic delivery system where the antibiotic is encapsulated into a blood component—platelet. Platelets have been previously reported as efficient drug delivery vehicles for targeting cancer cells. On the other hand, during platelet–bacterial interaction, platelets can act as covercytes. Keeping this in mind, smart antibiotic-loaded platelets have been used for killing bacterial cells. The loading of the antibiotic was done using its typical nature of engulfing surrounding small molecules. The water-soluble antibiotics were loaded directly into the platelet, whereas the hydrophobic antibiotics were preloaded in polycaprolactone (FDA-approved polymer)-based nanovesicles to make them solubilized prior to loading inside the platelets. The antibiotic-loaded platelets (containing hydrophilic antibiotics or hydrophobic antibiotic -encapsulated polymer nanoparticles) were found to be stable when studied through platelet aggregometry. The carrier showed bactericidal effects at a significantly lower concentration at which the free antibiotic has negligible efficacy. This could be attributed to the molecular confinement of the antibiotics inside the platelets, therefore causing localization of the drug and leading to efficient activity against bacteria. Interestingly, the smart antibiotic-loaded platelets were capable of killing the resistant strains too at the same lower concentration regime. Therefore, the antibiotic-loaded platelet could emerge as a potential strategy for efficient delivery of antibiotics with a significant reduction of the dose required to achieve the intended antibacterial efficacy. Moreover, this antibiotic delivery method can be very useful to minimize immunogenic responses due to antibiotic administration and to avoid the development of drug resistance due to the invisible mode of delivery.