Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release.

Autor: Chhabra R; WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, Ulm, Germany., Grabrucker AM; WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, Ulm, Germany; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany., Veratti P; Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy., Belletti D; Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy., Boeckers TM; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany., Vandelli MA; Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy., Forni F; Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy., Tosi G; Pharmaceutical Technology, Te.Far.T.I. group, Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy., Ruozi B; 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.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2014 Aug 25; Vol. 471 (1-2), pp. 349-57. Date of Electronic Publication: 2014 Jun 02.
DOI: 10.1016/j.ijpharm.2014.05.054
Abstrakt: 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.
(Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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