Preparation and characterization of a novel nonviral gene transfer system: procationic-liposome-protamine-DNA complexes.
Procationic-liposome-protamine-DNA (PLPD) vector, a novel nonviral gene delivery system, that may further adsorb transferrin (Tf) at its surface via electrostatic interactions to form Tf-PLPD, was prepared from soybean phosphatidylcholine (PC), cholesterol (Chol), and a kind of cholesterol derivative, CHETA(cholest-5-en-3-ol(3beta)-[2-[[4-[(carboxymethyl)dithio]-1-iminobutyl] amino] ethyl] carba- mate) containing disulfide bond by film dispersion-filteration method. Central composite design was used to optimize the formulation. The presence of serum did not affect the transfection activity of PLPD or Tf-PLPD and the cell viability was not affected significantly when the cells were incubated with the complexes for 4 hr at 37 degrees C. Compared with one kind of cationic liposomes(liposome-protamine-DNA), the PLPD had much less cytotoxicity to three hepar cell lines(including HepG2, SMMC7721, and Chang's normal heptocyte). The procationic lipoplex described here, combining the condensing effect of protamine and the targeting capability of Tf, was a perspective nonviral vector for gene delivery system.
Zhong
Zhi-Rong
ZR
Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University West China School of Pharmacy, Chengdu, Sichuan 610041, PR China. zrzzl@vip.sina.com
Liu
Ji
J
Deng
Yong
Y
Zhang
Zhi-Rong
ZR
Song
Qing-Guo
QG
Wei
Yan-Xia
YX
He
Qin
Q
D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D004337:Drug Carriers; D004563:Electrochemistry; D005079:Excipients; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011479:Protamines / Q000737:chemistry; D014162:Transfection
D002412:Cations; D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D011479:Protamines; D004247:DNA