UNSPECIFIED. (2005) PEG shielded polymeric double-layered micelles for gene delivery. JOURNAL OF CONTROLLED RELEASE, 102 (3). pp. 711-724. ISSN 0168-3659

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Abstract

A combination of A-B and B-C block copolymers was used to encapsulate DNA inside pEG coated particles, where A is a cationic block (poly(dimethylaminoethyl methacrylate), pDMAEMA) for DNA binding and condensation, B is a hydrophobic block (poly(butylmethacrylate), pBMA) and C is a polyethylene glycol (pEG) block. The AB and BC block copolymers were synthesized by transition metal mediated radical polymerization. The AB block copolymer had a fixed pBMA molecular weight of 3800 g/mol and a varying pDMAEMA molecular weight (from 22 to 65 kg/mol), the BC block copolymer had a fixed composition (pBMA 9000 g/mol; pEG 2000 g/mol). Plasmid DNA containing particles were made via a detergent dialysis method. By this method, particles of approximately 120 rim, as determined by dynamic light scattering (DLS), with a near neutral charge were formed, independent of the DMAEMA block size. DLS measurements and gel electrophoresis indicated that the particles were very stable in cell culture medium at 37 degreesC and resistant to anionic exchange by poly-L-aspartic acid. The particles were able to transfect COS-7 and OVCAR-3 cells with minor toxicity if incubated for I or 4 h; incubation for 24 h resulted in an increased toxicity. This paper shows that small polyplexes with near neutral charge can be obtained via a convenient detergent dialysis method using pDMAEMA-b-pBMA and pBMA-b-pEG. These particles may be interesting for in vivo experiments where particles with high positive charges have adverse interactions with blood components. (C) 2004 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry R Medicine > RS Pharmacy and materia medica
Journal or Publication Title:	JOURNAL OF CONTROLLED RELEASE
Publisher:	ELSEVIER SCIENCE BV
ISSN:	0168-3659
Date:	16 February 2005
Volume:	102
Number:	3
Number of Pages:	14
Page Range:	pp. 711-724
Identification Number:	10.1016/j.jconrel.2004.11.005
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/7350

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