Delivery and expression of pDNA embedded in collagen matrices.
Collagen matrices can be used as non-viral biocompatible gene carriers for localized implantable gene therapy. Collagen matrices embedding pDNA with enhanced binding through condensing agent linkage to the matrix or to the pDNA have been formulated, and characterized in various systems. pDNA and condensed pDNA were released intact from the matrices within 1-2 days. In vitro transfection with collagen matrices containing pDNA (luciferase encoding), pDNA in liposome (LIP), and pDNA with polyethylenimine (PEI) resulted in significantly higher expression levels in comparison to naked pDNA. pDNA-LIP matrices exhibited a dose response transfection of NIH 3T3, 293, MDA-MB-231 and smooth muscle cells (SMCs) in cell cultures. Subdermal implantations of collagen-polylysine-pDNA matrices in rats resulted in significantly higher gene expression levels in comparison to non-condensed pDNA matrices. Perivascular treatment with pDNA matrix and of naked pDNA solution in balloon-injured rat carotid arteries resulted in significant expression. In conclusion, a facile method for embedding cationic formulations of pDNA in collagen matrices was developed. These bioactive matrices seem to be suitable for tissue engineering and local gene therapy strategies.
Cohen-Sacks
Hagit
H
Department of Pharmaceutics, Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, Post Office Box 12065, 91120 Jerusalem, Israel.
Elazar
Victoria
V
Gao
Jianchuan
J
Golomb
Assaf
A
Adwan
Hassan
H
Korchov
Nikoly
N
Levy
Robert J
RJ
Berger
Martin R
MR
Golomb
Gershon
G
D016475:3T3 Cells; D000818:Animals; D020212:Carotid Artery Injuries / Q000503:physiopathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003094:Collagen; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D019344:Lactic Acid; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011091:Polyesters; D011094:Polyethyleneimine; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D011094:Polyethyleneimine; D003094:Collagen; D004247:DNA; D008156:Luciferases