Disulfide-linked liposomes: effective delivery vehicle for Bcl-2 antisense oligodeoxyribonucleotide G3139.
BACKGROUND
Disulfide-linked oligodeoxyribonucleotide (ODN) liposomes were formulated and evaluated for the delivery of antisense ODN G3139 in KB human oral carcinoma cells.


METHODS
Liposomes composed of 1,2-di-(9Z-octadecenoyl)-3-trimethylammo-nium-propane (DOTAP)/egg phosphatidylcholine/alpha-tocopheryl polyethylene glycol 1000 succinate were incorporated with hydrophobized disulfide-linked ODN. Disulfide-linked ODN liposomes were characterized for their size, ODN intracellular delivery, Bcl-2 mRNA and protein expression, growth inhibition, and chemosensitization.


RESULTS
Intracellular delivery of ODN with disulfide-linked ODN liposomes was more efficient than that with non-liposomal hydrophobized disulfide-linked ODN. Treatment of the cells with disulfide-linked ODN liposomes resulted in efficient Bcl-2 down-regulation greater than that with hydrophobized disulfide-linked ODN and consistent with that of cellular growth inhibition and the sensitization to daunorubicin in KB cells. Disulfide-linked ODN liposomes exhibited superior colloidal stability during 5-week storage.


CONCLUSIONS
Disulfide-linked liposomes are effective delivery vehicles for antisense ODN.
College of Pharmacy, The Ohio State University, 542 LM Parks Hall, 500 W. 12th Ave, Columbus, OH 43210, USA.
Wanlop
W
Weecharangsan
Bo
B
Yu
Shujun
S
Liu
Jiu Xia
JX
Pang
L James
LJ
Lee
Guido
G
Marcucci
Robert J
RJ
Lee
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D003102:Colloids / Q000008:administration & dosage / Q000737:chemistry; D003630:Daunorubicin / Q000494:pharmacology; D004220:Disulfides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D015536:Down-Regulation; D004355:Drug Stability; D019254:Genes, bcl-2; D006801:Humans; D007624:KB Cells; D008081:Liposomes / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D014162:Transfection / Q000379:methods*
D000903:Antibiotics, Antineoplastic; D003102:Colloids; D004220:Disulfides; D008081:Liposomes; D020319:Oligodeoxyribonucleotides, Antisense; D003630:Daunorubicin