Reference : Cationic Liposomes Carrying siRNA: Impact of Lipid Composition on Physicochemical Pro...
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/222557
Cationic Liposomes Carrying siRNA: Impact of Lipid Composition on Physicochemical Properties, Cytotoxicity and Endosomal Escape
English
Lechanteur, Anna mailto [Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique >]
Sanna, Vincent mailto [> >]
Duchemin, Amandine mailto [Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales >]
Evrard, Brigitte mailto [Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique >]
Mottet, Denis mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Piel, Géraldine mailto [Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique >]
24-Apr-2018
Nanomaterials
MDPI AG
8
5
Yes (verified by ORBi)
International
2079-4991
Basel
Switzerland
[en] Abstract: In recent year, cationic liposomes have gained a lot of attention for siRNA delivery. Despite this, intracellular barriers as endosomal escape and cytosolic delivery of siRNA still represent a challeng, as well as the cytotoxicity due to cationic lipids. To address these issues, we developed four liposomal formulations, composed of two different cationic lipids (DOTAP and DC-Cholesterol) and different ratio of co-lipids (cholesterol and DOPE). The objective is to dissect these impacts on siRNA efficacy and cytotoxicity. Liposomes were complexed to siRNA at six different N/P molar ratios, physico-chemical properties were characterized, and consequently, N/P 2.5, 5 and 10 were selected for in vitro experiments. We have shown that cytotoxicity is influenced by the N/P ratio, the concentration of cationic lipid, as well as the nature of the cationic lipid. For instance, cell viability decreased by 70% with liposomes composed of DOTAP/Cholesterol/DOPE 1/0.75/0.5 at a N/P ratio 10, whereas the same formulation at a N/P ratio of 2.5 was safe. Interestingly, we have observed differences in terms of mRNA knock-down efficiency, whereas the transfection rate was quite similar for each formulation. Liposomes containing 50% of DOPE induced a mRNA silencing of around 80%. This study allowed us to highlight crucial parameters in order to develop lipoplexes which are safe, and which induce an efficient intracytoplasmic release of siRNA.
Centre Interdisciplinaire de Recherche sur le Médicament - CIRM
http://hdl.handle.net/2268/222557
10.3390/nano8050270

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
nanomaterials-08-00270.pdfPublisher postprint1.01 MBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.