Long circulating biodegradable poly(phosphazene) nanoparticles surface modified with poly(phosphazene)-poly(ethylene...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacokinetics

Background:

• Biodegradable nanoparticles are promising drug delivery vehicles.
• Surface modification influences nanoparticle biodistribution and circulation time.
• Poly(organo phosphazene) and poly(lactide-co-glycolide) are common nanoparticle materials.

Purpose of the Study:

• To investigate the biodistribution of poly(organo phosphazene) nanoparticles surface-modified with a novel poly(organo phosphazene)-poly(ethylene oxide) copolymer (PF-PEO[5000]).
• To compare the biodistribution of PF-PEO[5000]-coated nanoparticles with those coated with a commercial copolymer (Poloxamine 908).
• To assess the impact of surface modification on nanoparticle circulation time and organ uptake in vivo.

Main Methods:

• Intravenous administration of nanoparticles to rats and rabbits.
• Biodistribution studies using quantitative analysis of nanoparticle distribution in various organs.
• Comparison of nanoparticle clearance rates and tissue sequestration between different surface coatings.

Main Results:

• Poly(organo phosphazene) nanoparticles coated with Poloxamine 908 were primarily captured by the liver.
• PF-PEO[5000]-coated poly(organo phosphazene) nanoparticles exhibited prolonged blood circulation and reduced liver sequestration.
• In rabbits, PF-PEO[5000]-coated nanoparticles showed extended systemic circulation and significant targeting to the bone marrow.

Conclusions:

• The nature of the nanoparticle surface coating significantly impacts biodistribution and pharmacokinetic profiles.
• PF-PEO[5000] surface modification enhances nanoparticle circulation time and reduces undesirable liver uptake.
• Surface-engineered nanoparticles hold potential for targeted delivery, including to bone marrow.