title: Drug Delivery Nanoparticles: Toxicity Comparison in Retinal Pigment Epithelium and Retinal Vascular Endothelial Cells.
abstract: Multiple synthetic polymer nanoparticles (NPs) have been widely used as drug delivery systems. However, their toxicity to the retinal pigment epithelium and retinal endothelium remains unclear. In this study, we analyze the cytotoxic effects of three different kinds of NPs, made of poly lactic-co-glycolic acid (PLGA), polycaprolactone (PCL), and PEGylated PLGA (PEG-PLGA), in a retinal pigment epithelium cell line (ARPE-19) and in primary human retinal vascular endothelial cells (RVEC). PEG-PLGA NPs presented the lowest cytotoxicity on ARPE-19 cells and RVEC as assessed by MTT viability assay. While PLGA and PCL exhibited variable amounts of toxicity, no significant toxicity was observed when incubating cells with high PEG-PLGA concentrations (100 µg/ml), for up to 6 days. On both transmission electron microscopy and confocal microscopy, Rhodamine 6G-loaded PEG-PLGA NPs were observed intracellularly in multiple subcellular organelles. PEG-PLGA NPs are a potentially viable option for the treatment of eye diseases.
authors.affiliation: a Retina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Haijiang
authors.initials: H
authors.lastname: Lin
authors.affiliation: a Retina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Yueran
authors.initials: Y
authors.lastname: Yue
authors.affiliation: a Retina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Maidana
authors.affiliation: a Retina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Peggy
authors.initials: P
authors.lastname: Bouzika
authors.affiliation: a Retina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Alp
authors.initials: A
authors.lastname: Atik
authors.affiliation: a Retina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: a Retina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.affiliation: a Retina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Demetrios G
authors.initials: DG
authors.lastname: Vavvas
mesh_terms: D002460:Cell Line; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D019344:Lactic Acid / Q000633:toxicity*; D053758:Nanoparticles; D011091:Polyesters / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000633:toxicity*; D011098:Polyglactin 910 / Q000633:toxicity*; D011100:Polyglycolic Acid / Q000633:toxicity*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055213:Retinal Pigment Epithelium / Q000187:drug effects*; D012171:Retinal Vessels / Q000166:cytology*
chemical_list: D011091:Polyesters; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols
keywords: Cellular uptake; PEG-PLGA; nanoparticle; pegylation; retina; subcellular localization