Reference : Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes:...
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/99331
Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: Benefits over classical vesicles.
English
Ducat, Emilie mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique >]
Deprez, Julie mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Gillet, Aline [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Evrard, Brigitte mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique >]
Peulen, Olivier mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Piel, Géraldine mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique >]
2011
International Journal of Pharmaceutics
Elsevier Science
Yes (verified by ORBi)
International
0378-5173
Amsterdam
The Netherlands
[en] peptide ; pH-sensitive liposomes ; drug delivery ; PEG ; cellular uptake
[en] The purpose of this study is to propose a suitable vector combining increased circulation lifetime and intracellular delivery capacities for a therapeutic peptide. Long circulating classical liposomes [SPC:CHOL:PEG-750-DSPE (47:47:6 molar% ratio)] or pH-sensitive stealth liposomes [DOPE:CHEMS:CHOL:PEG(750)-DSPE (43:21:30:6 molar% ratio)] were used to deliver a therapeutic peptide to its nuclear site of action. The benefit of using stealth pH-sensitive liposomes was investigated and formulations were compared to classical liposomes in terms of size, shape, charge, encapsulation efficiency, stability and, most importantly, in terms of cellular uptake. Confocal microscopy and flow cytometry were used to evaluate the intracellular fate of liposomes themselves and of their hydrophilic encapsulated material. Cellular uptake of peptide-loaded liposomes was also investigated in three cell lines: Hs578t human epithelial cells from breast carcinoma, MDA-MB-231 human breast carcinoma cells and WI-26 human diploid lung fibroblast cells. The difference between formulations in terms of peptide delivery from the endosome to the cytoplasm and even to the nucleus was investigated as a function of time. Characterization studies showed that both formulations possess acceptable size, shape and encapsulation efficiency but cellular uptake studies showed the important benefit of the pH-sensitive formulation over the classical one, in spite of liposome PEGylation. Indeed, stealth pH-sensitive liposomes were able to deliver hydrophilic materials strongly to the cytoplasm. Most importantly, when encapsulated in pH-sensitive stealth liposomes, the peptide was able to reach the nucleus of tumorigenic and non tumorigenic breast cancer cells.
Centre Interfacultaire de Recherche du Médicament - CIRM ; Giga-Cancer
Région wallonne : Direction générale des Technologies, de la Recherche et de l'Energie - DGTRE
Researchers
http://hdl.handle.net/2268/99331
10.1016/j.ijpharm.2011.08.034

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
International Journal of Pharmaceutics 2011 Ducat.pdfPublisher postprint1.9 MBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.