title: Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release.
abstract: Polymeric nanoparticles (NPs) offer a promising approach for therapeutic intracellular delivery of proteins, conventionally hampered by short half-lives, instability and immunogenicity. Remarkably, NPs uptake occurs via endocytic internalization leading to NPs content's release within lysosomes. To overcome lysosomal degradation and achieve NPs and/or loaded proteins release into cytosol, we propose the formulation of hybrid NPs by adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as pH sensitive component in the formulation of poly-lactide-co-glycolide (PLGA) NPs. Hybrid NPs, featured by different DOPE/PLGA ratios, were characterized in terms of structure, stability and lipid organization within the polymeric matrix. Experiments on NIH cells and rat primary neuronal cultures highlighted the safety profile of hybrid NPs. Moreover, after internalization, NPs are able to transiently destabilize the integrity of lysosomes in which they are taken up, speeding their escape and favoring cytoplasmatic localization. Thus, these DOPE/PLGA-NPs configure themselves as promising carriers for intracellular protein delivery.
authors.affiliation: WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, Ulm, Germany.
authors.forename: Resham
authors.initials: R
authors.lastname: Chhabra
authors.affiliation: WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, Ulm, Germany; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Grabrucker
authors.affiliation: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Veratti
authors.affiliation: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Belletti
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.affiliation: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy.
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Vandelli
authors.affiliation: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Forni
authors.affiliation: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tosi
authors.affiliation: Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy. Electronic address: barbara.ruozi@unimore.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruozi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D061251:Primary Cell Culture; D051381:Rats; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D013499:Surface Properties
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D004337:Drug Carriers; D010714:Phosphatidylethanolamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid
keywords: DOPE; Drug delivery; Endo-lysosomes; Nanoparticles (NPs); PLGA; Stability