title: Long circulating biodegradable poly(phosphazene) nanoparticles surface modified with poly(phosphazene)-poly(ethylene oxide) copolymer.
abstract: The biodistribution of biodegradable poly(organo phosphazene) nanoparticles surface modified by adsorption of a novel poly(organo phosphazene)-poly(ethylene oxide) copolymer with a 5000 M(W) PEO chain (PF-PEO[5000]), following intravenous administration in rats and rabbits, is described. The data are compared to the biodistribution of poly(organo phosphazene) and poly(lactide-co-glycolide) nanoparticles coated with a tetrafunctional copolymer of poly(ethylene oxide)-poly(propylene oxide) ethylenediamine, commercially available as Poloxamine 908. This copolymer has a PEO chain of the same size as the poly(organo phosphazene)-PEO derivative used. The results in the rat model reveal that poly(organo phosphazene) nanoparticles with a Poloxamine 908 coating were mainly captured by the liver, although a retardation in clearance from the systemic circulation was seen. In contrast, the poly(organo phosphazene) nanoparticles coated with PF-PEO(5000) showed a prolonged blood circulating profile, with only a small amount of the nanoparticles sequestered by the liver. This indicates the importance of the nature of both the anchoring group and the particle surface on the biological performances of the system. Study of the biodistribution of the PF-PEO(5000)-coated poly(organo phosphazene) nanoparticles in the rabbit model also indicated a prolonged systemic circulation lifetime and reduced liver uptake, whereby a significant amount of the administered nanoparticles was targeted to the bone marrow.
authors.affiliation: Department of Organic Chemistry, Biomaterials and Polymer Research Group, University of Ghent, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vandorpe
authors.forename: E
authors.initials: E
authors.lastname: Schacht
authors.forename: S
authors.initials: S
authors.lastname: Dunn
authors.forename: A
authors.initials: A
authors.lastname: Hawley
authors.forename: S
authors.initials: S
authors.lastname: Stolnik
authors.forename: S S
authors.initials: SS
authors.lastname: Davis
authors.forename: M C
authors.initials: MC
authors.lastname: Garnett
authors.forename: M C
authors.initials: MC
authors.lastname: Davies
authors.forename: L
authors.initials: L
authors.lastname: Illum
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D004337:Drug Carriers; D005029:Ethylenediamines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D005269:Femur / Q000378:metabolism; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008970:Molecular Weight; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D011409:Propylene Glycols / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D013154:Spleen / Q000378:metabolism; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D005029:Ethylenediamines; D009943:Organophosphorus Compounds; D011108:Polymers; D011409:Propylene Glycols; C108974:poly(phosphazene); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C012504:polypropylene glycol; D011100:Polyglycolic Acid; C012571:tetronic 701; D019344:Lactic Acid; D011092:Polyethylene Glycols