PMID- 26456916 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20220410 IS - 1872-8294 (Electronic) IS - 0169-409X (Print) IS - 0169-409X (Linking) VI - 99 IP - Pt A DP - 2016 Apr 1 TI - PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. PG - 28-51 LID - S0169-409X(15)00217-3 [pii] LID - 10.1016/j.addr.2015.09.012 [doi] AB - Coating the surface of nanoparticles with polyethylene glycol (PEG), or "PEGylation", is a commonly used approach for improving the efficiency of drug and gene delivery to target cells and tissues. Building from the success of PEGylating proteins to improve systemic circulation time and decrease immunogenicity, the impact of PEG coatings on the fate of systemically administered nanoparticle formulations has, and continues to be, widely studied. PEG coatings on nanoparticles shield the surface from aggregation, opsonization, and phagocytosis, prolonging systemic circulation time. Here, we briefly describe the history of the development of PEGylated nanoparticle formulations for systemic administration, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time. A less frequently discussed topic, we then describe how PEG coatings on nanoparticles have also been utilized for overcoming various biological barriers to efficient drug and gene delivery associated with other modes of administration, ranging from gastrointestinal to ocular. Finally, we describe both methods for PEGylating nanoparticles and methods for characterizing PEG surface density, a key factor in the effectiveness of the PEG surface coating for improving drug and gene delivery. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Suk, Jung Soo AU - Suk JS AD - The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States. FAU - Xu, Qingguo AU - Xu Q AD - The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States. FAU - Kim, Namho AU - Kim N AD - The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, United States. FAU - Hanes, Justin AU - Hanes J AD - The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, United States; Departments of Biomedical Engineering, Environmental and Health Sciences, Oncology, Neurosurgery, and Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD 21205 United States. FAU - Ensign, Laura M AU - Ensign LM AD - The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, United States. Electronic address: lensign@jhmi.edu. LA - eng GR - R01 EB020147/EB/NIBIB NIH HHS/United States GR - P30 AI094189/AI/NIAID NIH HHS/United States GR - P30AI094189/AI/NIAID NIH HHS/United States GR - R33 AI094519/AI/NIAID NIH HHS/United States GR - R01HL127413/HL/NHLBI NIH HHS/United States GR - U19AI133127/AI/NIAID NIH HHS/United States GR - R01 HL127413/HL/NHLBI NIH HHS/United States GR - R01 CA197111/CA/NCI NIH HHS/United States GR - R33AI094519/AI/NIAID NIH HHS/United States GR - U19 AI113127/AI/NIAID NIH HHS/United States GR - R01EB020147/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20151009 PL - Netherlands TA - Adv Drug Deliv Rev JT - Advanced drug delivery reviews JID - 8710523 RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Animals MH - *Drug Delivery Systems MH - *Gene Transfer Techniques MH - Humans MH - Nanoparticles/administration & dosage/*chemistry MH - Polyethylene Glycols/administration & dosage/*chemistry MH - Surface Properties PMC - PMC4798869 MID - NIHMS728497 OTO - NOTNLM OT - Enhanced permeability and retention (EPR) effect OT - Liposomes OT - Mononuclear phagocyte system (MPS) OT - Mucosal delivery OT - Stealth coatings EDAT- 2015/10/13 06:00 MHDA- 2016/12/15 06:00 PMCR- 2017/04/01 CRDT- 2015/10/13 06:00 PHST- 2015/06/27 00:00 [received] PHST- 2015/09/21 00:00 [revised] PHST- 2015/09/26 00:00 [accepted] PHST- 2015/10/13 06:00 [entrez] PHST- 2015/10/13 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2017/04/01 00:00 [pmc-release] AID - S0169-409X(15)00217-3 [pii] AID - 10.1016/j.addr.2015.09.012 [doi] PST - ppublish SO - Adv Drug Deliv Rev. 2016 Apr 1;99(Pt A):28-51. doi: 10.1016/j.addr.2015.09.012. Epub 2015 Oct 9.