title: Synthesis and in vivo pharmacokinetic evaluation of degradable shell cross-linked polymer nanoparticles with poly(carboxybetaine) versus poly(ethylene glycol) surface-grafted coatings.
abstract: Nanoparticles with tunable pharmacokinetics are desirable for various biomedical applications. Poly(ethylene glycol) (PEG) is well-known to create "stealth" effects to stabilize and extend the blood circulation of nanoparticles. In this work, poly(carboxybetaine) (PCB), a new nonfouling polymer material, was incorporated as surface-grafted coatings, conjugated onto degradable shell cross-linked knedel-like nanoparticles (dSCKs) composed of poly(acrylic acid)-based shells and poly(lactic acid) cores, to compare the in vivo pharmacokinetics to their PEG-functionalized analogues. A series of five dSCKs was prepared from amphiphilic block copolymers, having different numbers and lengths of either PEG or PCB grafts, by supramolecular assembly in water followed by shell cross-linking, and then studied by a lactate assay to confirm their core hydrolytic degradabilities. Each dSCK was also conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocyclic chelators and tyramine moieties to provide for (64)Cu and/or radiohalogen labeling. The high specific activity of (64)Cu radiolabeling ensured nanogram administration of dSCKs for in vivo evaluation of their pharmacokinetics. Biodistribution studies demonstrated comparable in vivo pharmacokinetic profiles of PCB-grafted dSCKs to their PEG-conjugated counterparts. These results indicated that PCB-functionalized dSCKs have great potential as a theranostic platform for translational research.
authors.affiliation: Departments of Chemistry and Chemical Engineering, Texas A&M University, College Station, Texas 77842, USA.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Luehmann
authors.forename: Guorong
authors.initials: G
authors.lastname: Sun
authors.forename: Sandani
authors.initials: S
authors.lastname: Samarajeewa
authors.forename: Jiong
authors.initials: J
authors.lastname: Zou
authors.forename: Shiyi
authors.initials: S
authors.lastname: Zhang
authors.forename: Fuwu
authors.initials: F
authors.lastname: Zhang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Liu
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wooley
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001622:Betaine / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009928:Organ Specificity; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D020099:Coated Materials, Biocompatible; D011109:Polymethacrylic Acids; C517178:polycarboxybetaine methacrylate; D001622:Betaine; D011092:Polyethylene Glycols