title: Engineering poly(ethylene glycol) particles for improved biodistribution.
abstract: We report the engineering of poly(ethylene glycol) (PEG) hydrogel particles using a mesoporous silica (MS) templating method via tuning the PEG molecular weight, particle size, and the presence or absence of the template and investigate the cell association and biodistribution of these particles. An ex vivo assay based on human whole blood that is more sensitive and relevant than traditional cell-line based assays for predicting in vivo circulation behavior is introduced. The association of MS@PEG particles (template present) with granulocytes and monocytes is higher compared with PEG particles (template absent). Increasing the PEG molecular weight (from 10 to 40 kDa) or decreasing the PEG particle size (from 1400 to 150 nm) reduces phagocytic blood cell association of the PEG particles. Mice biodistribution studies show that the PEG particles exhibit extended circulation times (>12 h) compared with the MS@PEG particles and that the retention of smaller PEG particles (150 nm) in blood, when compared with larger PEG particles (>400 nm), is increased at least 4-fold at 12 h after injection. Our findings highlight the influence of unique aspects of polymer hydrogel particles on biological interactions. The reported PEG hydrogel particles represent a new class of polymer carriers with potential biomedical applications.
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Cui
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: Karen
authors.initials: K
authors.lastname: Alt
authors.forename: Sheilajen
authors.initials: S
authors.lastname: Alcantara
authors.forename: Brett M
authors.initials: BM
authors.lastname: Paterson
authors.forename: Kang
authors.initials: K
authors.lastname: Liang
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Richardson
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Charmaine M
authors.initials: CM
authors.lastname: Jeffery
authors.forename: Roger I
authors.initials: RI
authors.lastname: Price
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Hagemeyer
authors.forename: Paul S
authors.initials: PS
authors.lastname: Donnelly
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
mesh_terms: D000818:Animals; D002460:Cell Line; D004738:Engineering; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D012822:Silicon Dioxide / Q000737:chemistry; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D011092:Polyethylene Glycols; D012822:Silicon Dioxide
keywords: PEG; biodistribution; cell association; hydrogel particles; mesoporous silica particles; nanoengineering