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Pharm Res. 2010 Nov;27(11):2260-73. doi: 10.1007/s11095-010-0092-z. Epub 2010 Mar 19.

pH-sensitive multi-PEGylated block copolymer as a bioresponsive pDNA delivery vector.

Author information

1
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin - Madison, 777 Highland Avenue, Madison, Wisconsin 53705-2222, USA.

Abstract

PURPOSE:

A reversibly-PEGylated diblock copolymer, poly(aspartate-hydrazide-poly(ethylene glycol))-block-poly(aspartate-diaminoethane) (p[Asp(Hyd-PEG)]-b-p[Asp(DET)]) was reported here for enhanced gene transfection and colloidal stability. The diblock copolymer possessed a unique architecture based on a poly(aspartamide) backbone. The first block, p[Asp(Hyd)], was used for multi-PEG conjugations, and the second block, p[Asp(DET)], was used for DNA condensation and endosomal escape.

METHODS:

p[Asp(Hyd-PEG)]-b-p[Asp(DET)] was synthesized and characterized by (1)H-NMR. Polyplexes were formed by mixing the synthesized polymers and pDNA. The polyplex size, ζ-potential, and in vitro transfection efficiency were determined by dynamic light scattering, ζ-potential measurements, and luciferase assays, respectively. pH-dependent release of PEG from the polymer was monitored by cationic-exchange chromatography.

RESULTS:

The polyplexes were 70-90 nm in size, and the surface charge was effectively shielded by a PEG layer. The transfection efficiency of the reversibly PEGylated polyplexes was confirmed to be comparable to that of the non-PEGylated counterparts and 1,000 times higher than that of the irreversibly PEGylated polyplexes. PEG release was demonstrated to be pH-sensitive. Fifty percent of the PEG was released within 30 min at pH 5, while the polymer incubated at pH 7.4 could still maintain 50% of PEG after 8 h.

CONCLUSION:

The reversibly PEGylated polyplexes were shown to maintain polyplex stability without compromising transfection efficiency.

PMID:
20300803
PMCID:
PMC2917510
DOI:
10.1007/s11095-010-0092-z
[Indexed for MEDLINE]
Free PMC Article
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