Daptomycin-Loaded Nano-Drug Delivery System Based on Biomimetic Cell Membrane Coating Technology: Preparation,...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Infectious Diseases

Background:

• Staphylococcus aureus (S. aureus) infections pose a significant threat due to multidrug resistance.
• Daptomycin (DAP) is crucial for treating resistant Gram-positive bacterial infections but faces limitations like short half-life and emerging resistance.
• Developing advanced drug delivery systems is vital to enhance DAP's efficacy and overcome clinical challenges.

Purpose of the Study:

• To engineer a biomimetic nano-drug delivery system for daptomycin (DAP).
• To improve DAP's targeting, prolong its circulation, and mitigate bacterial resistance.
• To create a novel strategy for overcoming daptomycin's clinical limitations.

Main Methods:

• Daptomycin-loaded chitosan nanocomposite particles (DAP-CS) were fabricated via electrostatic self-assembly.
• Macrophage membrane vesicles (MM) were prepared and fused with DMPC.
• A biomimetic system (DAP-CS@MM) was constructed using coextrusion, characterized for physicochemical properties, and evaluated in vitro and in vivo.

Main Results:

• The DAP-CS@MM nanoparticles measured 110.9 ± 13.72 nm with a zeta potential of +11.90 ± 1.90 mV and 70.43 ± 1.29% encapsulation efficiency.
• DAP-CS@MM retained functional macrophage membrane proteins, including TLR2 receptors, demonstrating enhanced immune escape.
• In vivo studies showed superior antibacterial efficacy of DAP-CS@MM against Staphylococcus aureus compared to DAP and DAP-CS.

Conclusions:

• The biomimetic DAP-CS@MM nano-drug delivery system demonstrates significant immune evasion capabilities.
• This novel system exhibits enhanced antibacterial performance, effectively overcoming daptomycin resistance.
• DAP-CS@MM presents a promising therapeutic strategy for managing challenging S. aureus infections.