TY - JOUR
T1 - Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release
AU - Chhabra, Resham
AU - Grabrucker, Andreas M.
AU - Veratti, Patrizia
AU - Belletti, Daniela
AU - Boeckers, Tobias M.
AU - Vandelli, Maria Angela
AU - Forni, Flavio
AU - Tosi, Giovanni
AU - Ruozi, Barbara
N1 - Copyright © 2014 Elsevier B.V. All rights reserved.
PY - 2014/8/25
Y1 - 2014/8/25
N2 - 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.
AB - 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.
KW - DOPE
KW - Drug delivery
KW - Endo-lysosomes
KW - Nanoparticles (NPs)
KW - PLGA
KW - Stability
UR - http://www.scopus.com/inward/record.url?scp=84902160464&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2014.05.054
DO - 10.1016/j.ijpharm.2014.05.054
M3 - Article
C2 - 24882034
AN - SCOPUS:84902160464
SN - 0378-5173
VL - 471
SP - 349
EP - 357
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -