Cyclodextrin-modified polyethylenimine polymers for gene delivery.
Linear and branched poly(ethylenimines), lPEI and bPEI, respectively, grafted with beta-cyclodextrin are prepared to give CD-lPEI and CD-bPEI, respectively, and are investigated as in vitro and in vivo nonviral gene delivery agents. The in vitro toxicity and transfection efficiency are sensitive to the level of cyclodextrin grafting. The cyclodextrin-containing polycations, when combined with adamantane-poly(ethylene glycol) (AD-PEG) conjugates, form particles that are stable at physiological salt concentrations. PEGylated CD-lPEI-based particles give in vitro gene expression equal to or greater than lPEI as measured by the percentage of EGFP expressing cells. Tail vein injections into mice of 120 microg of plasmid DNA formulated with CD-lPEI and AD-PEG do not reveal observable toxicities, and both nucleic acid accumulation and expression are observed in liver.
Pun
Suzie H
SH
Insert Therapeutics Inc., 2585 Nina Street, Pasadena, California 91107, USA.
Bellocq
Nathalie C
NC
Liu
Aijie
A
Jensen
Greg
G
Machemer
Todd
T
Quijano
Erlinda
E
Schluep
Thomas
T
Wen
Shufen
S
Engler
Heidrun
H
Heidel
Jeremy
J
Davis
Mark E
ME
D000818:Animals; D045744:Cell Line, Tumor; D003505:Cyclodextrins / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D015394:Molecular Structure; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000633:toxicity; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D012492:Salts / Q000494:pharmacology; D012997:Solvents; D017186:Titrimetry; D014162:Transfection
D003505:Cyclodextrins; D011108:Polymers; D012492:Salts; D012997:Solvents; D011094:Polyethyleneimine