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Red Blood Cell Membrane-Camouflaged Tedizolid Phosphate-Loaded PLGA Nanoparticles for Bacterial-Infection Therapy
Pharmaceutics ( IF 4.9 ) Pub Date : 2021-01-14 , DOI: 10.3390/pharmaceutics13010099
Xinyi Wu , Yichen Li , Faisal Raza , Xuerui Wang , Shulei Zhang , Ruonan Rong , Mingfeng Qiu , Jing Su

Multiple drug resistance (MDR) in bacterial infections is developed with the abuse of antibiotics, posing a severe threat to global health. Tedizolid phosphate (TR-701) is an efficient prodrug of tedizolid (TR-700) against gram-positive bacteria, including methicillin-sensitive staphylococcus aureus (MSSA) and methicillin-resistant staphylococcus aureus (MRSA). Herein, a novel drug delivery system: Red blood cell membrane (RBCM) coated TR-701-loaded polylactic acid-glycolic acid copolymer (PLGA) nanoparticles (RBCM-PLGA-TR-701NPs, RPTR-701Ns) was proposed. The RPTR-701Ns possessed a double-layer core-shell structure with 192.50 ± 5.85 nm in size, an average encapsulation efficiency of 36.63% and a 48 h-sustained release in vitro. Superior bio-compatibility was confirmed with red blood cells (RBCs) and HEK 293 cells. Due to the RBCM coating, RPTR-701Ns on one hand significantly reduced phagocytosis by RAW 264.7 cells as compared to PTR-701Ns, showing an immune escape effect. On the other hand, RPTR-701Ns had an advanced exotoxins neutralization ability, which helped reduce the damage of MRSA exotoxins to RBCs by 17.13%. Furthermore, excellent in vivo bacteria elimination and promoted wound healing were observed of RPTR-701Ns with a MRSA-infected mice model without causing toxicity. In summary, the novel delivery system provides a synergistic antibacterial treatment of both sustained release and bacterial toxins absorption, facilitating the incorporation of TR-701 into modern nanotechnology.

中文翻译:

红细胞膜伪装的替地唑利磷酸酯负载的PLGA纳米颗粒用于细菌感染治疗

滥用抗生素会导致细菌感染的多重耐药(MDR),对全球健康构成严重威胁。磷酸Tedizolid(TR-701)是泰替唑(TR-700)对革兰氏阳性细菌(包括对甲氧西林敏感的金黄色葡萄球菌(MSSA)和耐甲氧西林的金黄色葡萄球菌(MRSA))的有效前药。本文中,提出了一种新型的药物递送系统:涂有红细胞膜(RBCM)的TR-701负载的聚乳酸-乙醇酸共聚物(PLGA)纳米粒子(RBCM-PLGA-TR-701NPs,RPTR-701Ns)。RPTR-701N具有双层核-壳结构,密度为192.50±尺寸为5.85 nm,平均封装效率为36.63%,体外释放时间为48 h。红细胞(RBC)和HEK 293细胞证实了优异的生物相容性。由于具有RBCM涂层,与PTR-701Ns相比,一方面RPTR-701Ns显着减少了RAW 264.7细胞的吞噬作用,显示出免疫逃逸作用。另一方面,RPTR-701Ns具有先进的外毒素中和能力,可将MRSA外毒素对RBC的伤害降低17.13%。此外,使用MRSA感染的小鼠模型观察到RPTR-701Ns具有出色的体内细菌清除能力和促进的伤口愈合能力,而没有引起毒性。总而言之,新颖的递送系统可对缓释和细菌毒素的吸收提供协同抗菌治疗,
更新日期:2021-01-14
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