Stabilized lipid coated lipoplexes for the delivery of antisense oligonucleotides to liver endothelial cells in vitro and in vivo

被引:16
作者
Bartsch, M
Weeke-Klimp, AH
Hoenselaar, EPD
Stuart, MCA
Meijer, DKF
Scherphof, GL
Kamps, JAAM
机构
[1] Univ Groningen, Dept Pathol & Lab Med Med Biol, GUIDE, NL-9713 GZ Groningen, Netherlands
[2] Univ Groningen, Dept Cell Biol, GUIDE, Groningen, Netherlands
[3] Univ Groningen, Dept Phys Organ Chem, Stratingh Inst, Groningen, Netherlands
[4] Univ Groningen, Dept Pharmacokinet & Drug Delivery, GUIDE, Groningen, Netherlands
关键词
antisense oligonucleotides; ICAM-1; non-viral vector; PEG-stabilized; long circulating; targeted delivery;
D O I
10.1080/10611860400013519
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We report on the preparation and in vivo / in vitro disposition of antisense ODN encapsulating coated cationic lipoplexes (CCLs), prepared by a procedure essentially developed by Stuart and Allen (Stuart, D.D. and Allen, T.M. (2000) "A new liposomal formulation for antisense oligodeoxynucleotides with small size, high incorporation efficiency and good stability", Biochim. Biophys. Acta 1463 , pp. 219-229). The behavior of untargeted CCLs was compared with CCLs that were targeted to scavenger receptors on liver endothelial cells by covalent coupling of the poly-anion aconitylated human serum albumin (Aco-HSA) to the particle surface. By means of cryo transmission electron microscopy (cryo-TEM) particles of high electron density could be distinguished from electron-translucent particles, representing high and low ODN encapsulation, respectively. The two populations were separated by sucrose density gradient centrifugation. Upon injection into rats, the untargeted particles showed long circulating properties with a half-life of >10 h. These untargeted CCLs barely bound to liver endothelial cells in vitro while Aco-HSA CCLs massively and specifically interacted with scavenger receptors on these cells. With J774 cells, a macrophage cell line expressing scavenger receptors, downregulation of ICAM-1 mRNA levels was achieved when the ODN was specifically delivered by Aco-HSA targeted CCLs.
引用
收藏
页码:613 / 621
页数:9
相关论文
共 31 条
[1]   Drug delivery systems: Entering the mainstream [J].
Allen, TM ;
Cullis, PR .
SCIENCE, 2004, 303 (5665) :1818-1822
[2]   Massive and selective delivery of lipid-coated cationic lipoplexes of oligonucleotides targeted in vivo to hepatic endothelial cells [J].
Bartsch, M ;
Weeke-Klimp, AH ;
Meijer, DKF ;
Scherphof, GL ;
Kamps, JAAM .
PHARMACEUTICAL RESEARCH, 2002, 19 (05) :676-680
[3]  
Bligh E.G. Dyer., 1959, Can J Biochem Physiol, V37, P911, DOI [10.1139/y59-099, DOI 10.1139/O59-099]
[4]   A RAPID AND SENSITIVE SUB-MICRO PHOSPHORUS DETERMINATION [J].
BOETTCHER, C ;
PRIES, C ;
VANGENT, CM .
ANALYTICA CHIMICA ACTA, 1961, 24 (02) :203-&
[5]   Targeted delivery system for antisense oligonucleotides: a novel experimental strategy for neuroblastoma treatment [J].
Brignole, C ;
Pagnan, G ;
Marimpietri, D ;
Cosimo, E ;
Allen, TM ;
Ponzoni, M ;
Pastorino, F .
CANCER LETTERS, 2003, 197 (1-2) :231-235
[6]   Different intrahepatic distribution of phosphatidylglycerol and phosphatidylserine liposomes in the rat [J].
Daemen, T ;
Velinova, M ;
Regts, J ;
deJager, M ;
Kalicharan, R ;
Donga, J ;
vanderWant, JJL ;
Scherphof, GL .
HEPATOLOGY, 1997, 26 (02) :416-423
[7]   Vehicles for oligonucleotide delivery to tumours [J].
Dass, CR .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2002, 54 (01) :3-27
[8]   Particle-mediated intravascular delivery of oligonucleotides to tumors: Associated biology and lessons from genotherapy [J].
Dass, CR ;
Su, T .
DRUG DELIVERY, 2001, 8 (04) :191-213
[9]  
Fattal E, 2001, STP PHARMA SCI, V11, P31
[10]  
KAMPS JAA, 2001, CELLS HEPATIC SINUSO, V8, P144