pH-Sensitive Multi-PEGylated Block Copolymer as a Bioresponsive pDNA Delivery Vector
- Tsz Chung LaiAffiliated withDivision of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin – Madison
- , Younsoo BaeAffiliated withDivision of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky
- , Takayuki YoshidaAffiliated withAstellas Pharma Inc.
- , Kazunori KataokaAffiliated withDepartment of Materials Engineering, Graduate School of Engineering, The University of Tokyo
- , Glen S. KwonAffiliated withDivision of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin – Madison Email author
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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.
p[Asp(Hyd-PEG)]-b-p[Asp(DET)] was synthesized and characterized by 1H-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.
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.
The reversibly PEGylated polyplexes were shown to maintain polyplex stability without compromising transfection efficiency.
KEY WORDSnon-viral gene delivery PEG pH-sensitive polyplex
- pH-Sensitive Multi-PEGylated Block Copolymer as a Bioresponsive pDNA Delivery Vector
Volume 27, Issue 11 , pp 2260-2273
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- non-viral gene delivery
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- 1. Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin – Madison, 777 Highland Avenue, Madison, Wisconsin, 53705-2222, USA
- 2. Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky, 40536-0082, USA
- 3. Astellas Pharma Inc., 180, Ozumi, Yaizu-shi, Shizuoka, 425-0072, Japan
- 4. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan