PMID- 14648641
OWN - NLM
STAT- MEDLINE
DCOM- 20040412
LR  - 20191210
IS  - 0022-3549 (Print)
IS  - 0022-3549 (Linking)
VI  - 93
IP  - 1
DP  - 2004 Jan
TI  - Compositional effects of cationic lipid/DNA delivery systems on transgene 
      expression in cell culture.
PG  - 108-23
AB  - Studies of the contribution of various physical properties of cationic lipid/DNA 
      complexes (CLDCs) to their observed transgene expression in vitro were conducted 
      using cationic liposomes composed of the cationic lipids 
      1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and dimethyldioctadecylammonium 
      bromide (DDAB), with or without equimolar amounts of cholesterol (CHOL) or 
      1,2-dioleoylphosphatidylethanolamine (DOPE). The relative degree of luciferase 
      expression by CLDCs is dependent on a complex relationship between net charge of 
      the CLDC as well as previously reported properties, such as membrane fluidity and 
      curvature of the cationic bilayer. Assessments were made of the role of these 
      physical properties on CLDC stability in the extracellular medium, the extent of 
      DNA cellular association, and membrane disruption activity. The efficiency of 
      luciferase expression from negatively charged CLDCs is greatly improved by 
      incorporation of DOPE. This result correlates with enhanced resistance to 
      inhibition of gene delivery by heparan sulfate, increased cellular association of 
      DNA, and enhanced membrane disruption activity. Luciferase expression by 
      positively charged CLDCs is greatly reduced by incorporating equimolar amounts of 
      CHOL and DOPE. This result occurs is in spite of increased resistance to heparan 
      sulfate-mediated inhibition of gene delivery, increased DNA cellular association, 
      and enhanced membrane disruption activity. The observed CLDC compositional 
      effects on luciferase expression along with observed effects on the delivery 
      process suggest that a better understanding of the kinetics and specific routes 
      of gene delivery is necessary.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Wiethoff, Christopher M
AU  - Wiethoff CM
AD  - Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant 
      Avenue, Lawrence, Kansas 66047, USA.
FAU - Koe, Janet G
AU  - Koe JG
FAU - Koe, Gary S
AU  - Koe GS
FAU - Middaugh, C Russell
AU  - Middaugh CR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Cations)
RN  - 0 (Lipids)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - COS Cells
MH  - Cations
MH  - Cell Survival/drug effects/physiology
MH  - Chlorocebus aethiops
MH  - Cricetinae
MH  - DNA/*administration & dosage/genetics
MH  - Drug Delivery Systems/*methods
MH  - Gene Expression Regulation/genetics
MH  - *Gene Transfer Techniques
MH  - Genetic Therapy/methods
MH  - Lipids/*administration & dosage/genetics
MH  - Transgenes/*genetics
EDAT- 2003/12/04 05:00
MHDA- 2004/04/13 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/04/13 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - S0022-3549(16)31394-6 [pii]
AID - 10.1002/jps.10519 [doi]
PST - ppublish
SO  - J Pharm Sci. 2004 Jan;93(1):108-23. doi: 10.1002/jps.10519.