title: The effect of hyperbranched polyglycerol coatings on drug delivery using degradable polymer nanoparticles.
abstract: A key attribute for nanoparticles (NPs) that are used in medicine is the ability to avoid rapid uptake by phagocytic cells in the liver and other tissues. Poly(ethylene glycol) (PEG) coatings has been the gold standard in this regard for several decades. Here, we examined hyperbranched polyglycerols (HPG) as an alternate coating on NPs. In earlier work, HPG was modified with amines and subsequently conjugated to poly(lactic acid) (PLA), but that approach compromised the ability of HPG to resist non-specific adsorption of biomolecules. Instead, we synthesized a copolymer of PLA-HPG by a one-step esterification. NPs were produced from a single emulsion using PLA-HPG: fluorescent dye or the anti-tumor agent camptothecin (CPT) were encapsulated at high efficiency in the NPs. PLA-HPG NPs were quantitatively compared to PLA-PEG NPs, produced using approaches that have been extensively optimized for drug delivery in humans. Despite being similar in size, drug release profile and in vitro cytotoxicity, the PLA-HPG NPs showed significantly longer blood circulation and significantly less liver accumulation than PLA-PEG. CPT-loaded PLA-HPG NPs showed higher stability in suspension and better therapeutic effectiveness against tumors in vivo than CPT-loaded PLA-PEG NPs. Our results suggest that HPG is superior to PEG as a surface coating for NPs in drug delivery.
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, MEC 414, New Haven, CT 06511, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, MEC 414, New Haven, CT 06511, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Saucier-Sawyer
authors.affiliation: Department of Medical Oncology, Yale University, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoimes
authors.affiliation: Department of Chemical and Environmental Engineering, Yale University, 55 Prospect Street, MEC 414, New Haven, CT 06511, USA.
authors.forename: Junwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, MEC 414, New Haven, CT 06511, USA.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Seo
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, MEC 414, New Haven, CT 06511, USA.
authors.forename: Jillian W
authors.initials: JW
authors.lastname: Andrejecsk
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, MEC 414, New Haven, CT 06511, USA. Electronic address: mark.saltzman@yale.edu.
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000494:pharmacology / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D007150:Immunohistochemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D011108:Polymers; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D002166:Camptothecin
keywords: Camptothecin; Hyperbranched polyglycerol; Nanoparticles; Polylactic acid; Surface coating