title: Distribution and Cellular Uptake of PEGylated Polymeric Particles in the Lung Towards Cell-Specific Targeted Delivery.
abstract: OBJECTIVE
  We evaluated the role of a poly(ethylene glycol) (PEG) surface coating to increase residence times and alter the cellular fate of nano- and microparticles delivered to the lung.
  
  
  METHODS
  Three sizes of PRINT hydrogel particles (80 × 320 nm, 1.5 and 6 μm donuts) with and without a surface PEG coating were instilled in the airways of C57/b6 mice. At time points of 1, 7, and 28 days, BALF and whole lungs were evaluated for the inflammatory cytokine Il-6 and chemokine MIP-2, histopathology, cellular populations of macrophages, dendritic cells (DCs), and granulocytes, and particulate uptake within these cells through flow cytometry, ELISAs, and fluorescent imaging.
  
  
  RESULTS
  Particles of all sizes and surface chemistries were readily observed in the lung with minimal inflammatory response at all time points. Surface modification with PEGylation was found to significantly increase lung residence times and homogeneous lung distribution, delaying macrophage clearance of all sizes, with the largest increase in residence time observed for 80 × 320 nm particles. Additionally, it was observed that DCs were recruited to the airway following administration of unPEGylated particles and preferentially associated with these particles.
  
  
  CONCLUSIONS
  Pulmonary drug delivery vehicles designed with a PEG surface coating can be used to delay particle uptake and promote cell-specific targeting of therapeutics.
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Tammy W
authors.initials: TW
authors.lastname: Shen
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, 27695, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Fromen
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, 27695, USA.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Kai
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Luft
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Tojan B
authors.initials: TB
authors.lastname: Rahhal
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Robbins
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA. desimone@unc.edu.|Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, 27695, USA. desimone@unc.edu.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA. desimone@unc.edu.|Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA. desimone@unc.edu.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DeSimone
mesh_terms: D000818:Animals; D002460:Cell Line; D054426:Chemokine CXCL2 / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism*
chemical_list: D054426:Chemokine CXCL2; D015850:Interleukin-6; D011108:Polymers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols
keywords: Microparticle; Nanoparticle; PEGylation; Pulmonary drug delivery