Sarkar Sounik, Thapa Roshni, Naushin Farzana, Gupta Saurabh, Bhar Biswajit, De Rajib, Bhattacharya Jaydeep
School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India.
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India.
ACS Omega. 2022 Jul 1;7(28):24102-24110. doi: 10.1021/acsomega.1c07249. eCollection 2022 Jul 19.
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.
微生物致病机制被认为是全球最严峻的健康挑战之一。尽管已采购并使用了多种抗生素，但微生物常常能够逃脱并对抗生素产生耐药性。因此，发现新型抗生素并设计其智能递送方法至关重要。在许多情况下，使用脂质或聚合物等外来化学物质的递送剂会引发不同程度的免疫反应，且循环时间较短并存在突释现象。在当前的研究中，我们设计了一种新型抗生素递送系统，即将抗生素封装到血液成分——血小板中。血小板此前已被报道为靶向癌细胞的高效药物递送载体。另一方面，在血小板与细菌相互作用过程中，血小板可充当“覆盖细胞”。考虑到这一点，装载了智能抗生素的血小板已被用于杀灭细菌细胞。抗生素的装载利用了其吞噬周围小分子的典型特性。水溶性抗生素直接装载到血小板中，而疏水性抗生素则预先装载在基于聚己内酯（美国食品药品监督管理局批准的聚合物）的纳米囊泡中，使其在装载到血小板内部之前可溶解。通过血小板聚集试验研究发现，装载抗生素的血小板（含有亲水性抗生素或封装有疏水性抗生素的聚合物纳米颗粒）是稳定的。该载体在显著更低的浓度下就显示出杀菌效果，而在该浓度下游离抗生素的疗效可忽略不计。这可能归因于抗生素在血小板内的分子限制，从而导致药物定位并产生高效的抗菌活性。有趣的是，装载智能抗生素的血小板在相同的低浓度范围内也能够杀灭耐药菌株。因此，装载抗生素的血小板可能成为一种潜在策略，用于高效递送抗生素，同时大幅降低达到预期抗菌效果所需的剂量。此外，这种抗生素递送方法对于最大限度减少因抗生素给药引起的免疫反应以及避免因不可见的递送方式导致的耐药性发展可能非常有用。
