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 neuronal cells and rat primary 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

Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release / Resham, Chhabra; Andreas M., Grabrucker; Veratti, Patrizia; Belletti, Daniela; Tobias M., Boeckers; Vandelli, Maria Angela; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - STAMPA. - 471(2014), pp. 349-357. [10.1016/j.ijpharm.2014.05.054]

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

VERATTI, PATRIZIA;BELLETTI, Daniela;VANDELLI, Maria Angela;FORNI, Flavio;TOSI, Giovanni;RUOZI, Barbara
2014

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 neuronal cells and rat primary 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
471
349
357
Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release / Resham, Chhabra; Andreas M., Grabrucker; Veratti, Patrizia; Belletti, Daniela; Tobias M., Boeckers; Vandelli, Maria Angela; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - STAMPA. - 471(2014), pp. 349-357. [10.1016/j.ijpharm.2014.05.054]
Resham, Chhabra; Andreas M., Grabrucker; Veratti, Patrizia; Belletti, Daniela; Tobias M., Boeckers; Vandelli, Maria Angela; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara
File in questo prodotto:
File Dimensione Formato  
Chhabra et al., 2014, 471, 349.357.2014.pdf

non disponibili

Tipologia: Post-print dell'autore (bozza post referaggio)
Dimensione 2.52 MB
Formato Adobe PDF
2.52 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1017737
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 18
social impact