Article (Scientific journals)
Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: Benefits over classical vesicles.
Ducat, Emilie; Deprez, Julie; Gillet, Aline et al.
2011In International Journal of Pharmaceutics
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Keywords :
peptide; pH-sensitive liposomes; drug delivery; PEG; cellular uptake
Abstract :
[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.
Research center :
Centre Interfacultaire de Recherche du Médicament - CIRM
Giga-Cancer - ULiège
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Ducat, Emilie ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Deprez, Julie ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Gillet, Aline ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Evrard, Brigitte  ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
Peulen, Olivier   ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Piel, Géraldine  ;  Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique
 These authors have contributed equally to this work.
Language :
English
Title :
Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: Benefits over classical vesicles.
Publication date :
2011
Journal title :
International Journal of Pharmaceutics
ISSN :
0378-5173
eISSN :
1873-3476
Publisher :
Elsevier Science, Amsterdam, Netherlands
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
DGTRE - Région wallonne. Direction générale des Technologies, de la Recherche et de l'Énergie [BE]
Available on ORBi :
since 28 September 2011

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