In vivo gene transfection via intravitreal injection of cationic liposome/plasmid DNA complexes in rabbits.

Abstract:

:To optimize the in vivo ocular transfection efficiency of plasmid DNA (pDNA)/cationic liposome complexes, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/dioleoylphosphatidylethanolamine (DOPE) (1:1 molar ratio) liposomes and DOTMA/cholesterol (Chol) (1:1 molar ratio) liposomes were prepared with varying amounts of pDNA. pDNA/cationic liposome complexes were intravitreally injected (100 microL) in rabbits, and luciferase activity in the cornea, aqueous humor, iris-ciliary body, lens, vitreous body, and retina was measured. Transfection efficiency of pDNA alone did not change with pDNA ranging from 40 to 85 mg. In contrast, transfection efficiency of pDNA complexed with DOTMA/Chol liposomes significantly increased with the amount of pDNA ranging from 40 to 85 microg (P < 0.05). pDNA complexed with DOTMA/DOPE liposomes could not be prepared with pDNA greater than 60 microg. Among these experiments, pDNA (85 microg) complexed with DOTMA/Chol liposomes (pDNA:cationic liposome charge ratio (- : +) = 1.0:2.0) showed the highest transfection efficiency in the ocular tissue and its transfection-mediated luciferase activity peaked at 3 days. Among the ocular tissues, the highest gene expression was observed in the aqueous humor.

journal_name

Int J Pharm

authors

Kawakami S,Harada A,Sakanaka K,Nishida K,Nakamura J,Sakaeda T,Ichikawa N,Nakashima M,Sasaki H

doi

10.1016/j.ijpharm.2004.03.013

keywords:

subject

Has Abstract

pub_date

2004-07-08 00:00:00

pages

255-62

issue

2

eissn

0378-5173

issn

1873-3476

pii

S0378517304002017

journal_volume

278

pub_type

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