Abstract：
The emergence of antibiotic resistance makes the treatment of bacterial infections difficult and necessitates the development of alternative strategies. Targeted drug delivery systems are attracting great interest in overcoming the limitations of traditional antibiotics. Here, we aimed for targeted delivery of rifaximin (RFX) by decorating RFX-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) with synthetic P6.2 peptide, which was used as a targeting agent for the first time. Our results showed that encapsulation of RFX into NPs increased its antibacterial activity by improving its solubility and providing controlled release, while P6.2 modification allowed targeting of NPs to S. aureus bacterial cells. A promising therapeutic approach for bacterial infections, these P6.2-conjugated RFX-loaded PLGA NPs (TR-NP) demonstrated potent antibacterial activity against both strains of S. aureus. The antibacterial activity of RFX-loaded PLGA NPs (R-NP) showed significant results with an increase of 8 and 16-fold compared to free RFX against S. aureus and MRSA, respectively. Moreover, the activity of targeted nanoparticles was found to be increased 32 or 16-fold with an MBC value of 0.0078 μg/mL. All nanoparticles were found to be biocompatible at doses where they showed antimicrobial activity. Finally, it revealed that P6.2-conjugated targeted nanoparticles extremely accumulated in S. aureus rather than E. coli.
摘要：
抗生素耐药性的出现使得细菌感染的治疗变得困难并且需要开发替代策略。靶向药物递送系统在克服传统抗生素的局限性方面引起了极大的兴趣。这里,我们旨在通过用合成的P6.2肽装饰RFX负载的聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒（NP）来靶向递送利福昔明（RFX），首次用作靶向剂。我们的结果表明，将RFX封装到NP中通过改善其溶解度和提供受控释放来增加其抗菌活性，而P6.2修饰允许将NP靶向金黄色葡萄球菌细菌细胞。一种有希望的治疗细菌感染的方法，这些P6.2缀合的RFX负载的PLGANP（TR-NP）对金黄色葡萄球菌的两种菌株均表现出有效的抗菌活性。负载RFX的PLGANP（R-NP）的抗菌活性显示出显着的结果，与游离RFX相比，对金黄色葡萄球菌和MRSA分别增加了8和16倍，分别。此外，发现靶向纳米颗粒的活性增加了32或16倍，MBC值为0.0078μg/mL。发现所有纳米颗粒在它们显示抗微生物活性的剂量下是生物相容的。最后,它揭示了P6.2缀合的靶向纳米颗粒在金黄色葡萄球菌而不是大肠杆菌中极端积累。
