Abstract
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.
Highlights
Multiple drug resistance (MDR) of bacteria has posed significant clinical challenges to human health worldwide [1,2]
Tedizolid phosphate (TR-701) is a novel antibiotic approved for acute bacterial skin and skin structure infection (ABSSSI) caused by gram-positive bacteria, including methicillinsensitive staphylococcus aureus (MSSA) and methicillin-resistant staphylococcus aureus (MRSA) [6,7]
It indicated that red blood cell membrane (RBCM) was successfully coated onto the surface of PTR-701Ns
Summary
Multiple drug resistance (MDR) of bacteria has posed significant clinical challenges to human health worldwide [1,2]. Tedizolid phosphate (TR-701) is a novel antibiotic approved for acute bacterial skin and skin structure infection (ABSSSI) caused by gram-positive bacteria, including methicillinsensitive staphylococcus aureus (MSSA) and MRSA [6,7] It has demonstrated high efficacy and safety both in vitro and in vivo [8,9,10,11]. For better treatment of bacterial infection, numerous delivery systems have been explored and nanomedicine becomes a promising delivery strategy of antimicrobial [15,16] Metal nanoparticles such as silver, titanium dioxide and gold showed good antibacterial efficacy [17,18], but the risk of leaking out metallics may cause damage to health [19].
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