Ultradeformable cationic liposomes for delivery of small interfering RNA (siRNA) into human primary melanocytes.
The aim of this work was to develop a system that can deliver siRNA into cells present in the human epidermis. More specifically, we wanted to block the expression of a specific Myosin Va exon F containing isoform that is physiologically involved in melanosome transport in human melanocytes. Therefore, we prepared and investigated the capacity of ultradeformable cationic liposomes (UCLs) to deliver siRNA in hard-to-transfect human primary melanocytes. UCLs were formulated from different w:w ratios (6:1, 8:1 and 10:1) of the cationic lipid 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and the edge activator sodium cholate. Subsequently, UCL/siRNA complexes were prepared and their particle size, surface charge, deformability, cytotoxicity, transfection efficiency and long-term stability were tested. The best results were obtained with UCLs composed of a DOTAP/NaChol ratio of 6:1 (w:w) which are promising for future in vivo experiments.
Geusens
B
B
Department of Dermatology, Ghent University Hospital, Belgium. Barbara.Geusens@Ugent.be
Lambert
J
J
De Smedt
S C
SC
Buyens
K
K
Sanders
N N
NN
Van Gele
M
M
D002412:Cations / Q000737:chemistry; D002470:Cell Survival; D002478:Cells, Cultured; D020285:Cryoelectron Microscopy; D004355:Drug Stability; D004560:Electricity; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D008851:Micropore Filters; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D020358:Sodium Cholate / Q000737:chemistry; D014162:Transfection / Q000379:methods*
D002412:Cations; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; C077511:MYO5A protein, human; D024701:Myosin Type V; D018995:Myosin Heavy Chains; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; D020358:Sodium Cholate