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Red Blood Cell Membrane-Camouflaged Tedizolid Phosphate-Loaded PLGA Nanoparticles for Bacterial-Infection Therapy
Xinyi Wu1, Yichen Li1, Faisal Raza1
1School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
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.
Insights
A new red blood cell membrane-coated nanoparticle system delivers tedizolid phosphate (TR-701) effectively against antibiotic-resistant bacteria. This novel drug delivery enhances bacterial elimination and wound healing while neutralizing harmful toxins.
Area of Science:
- Biotechnology
- Nanotechnology
- Infectious Diseases
Background:
- Antibiotic abuse drives multiple drug resistance (MDR), a major global health threat.
- Tedizolid phosphate (TR-701) is an effective antibiotic against Gram-positive bacteria like MRSA.
- Novel drug delivery systems are needed to combat MDR infections.
Purpose of the Study:
- To develop and characterize a novel red blood cell membrane-coated nanoparticle system for TR-701 delivery.
- To evaluate the immune escape, exotoxin neutralization, and therapeutic efficacy of the developed system.
- To assess the in vivo performance and safety of the nanoparticle system in a mouse model.
Main Methods:
- Fabrication of red blood cell membrane (RBCM)-coated PLGA nanoparticles loaded with TR-701 (RBCM-PLGA-TR-701NPs).
- Characterization of nanoparticle size, encapsulation efficiency, and in vitro release kinetics.
- Assessment of biocompatibility, phagocytosis by macrophages, and exotoxin neutralization.
- Evaluation of in vivo antibacterial activity and wound healing in a MRSA-infected mouse model.
Main Results:
- RPTR-701Ns exhibited a core-shell structure (192.50 ± 5.85 nm) with 36.63% encapsulation efficiency and 48h sustained release.
- RPTR-701Ns demonstrated superior biocompatibility and immune escape by reducing phagocytosis.
- Significant reduction in MRSA exotoxin damage to RBCs (17.13%) and enhanced in vivo bacterial clearance and wound healing were observed.
- The system showed no significant toxicity in vivo.
Conclusions:
- The novel RBCM-coated nanoparticle system offers a synergistic antibacterial approach combining sustained drug release and toxin absorption.
- This nanotechnology-based delivery system enhances the therapeutic potential of tedizolid phosphate against MDR bacterial infections.
- RPTR-701Ns represent a promising strategy for combating challenging bacterial infections like MRSA.
