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pH-Sensitive Multi-PEGylated Block Copolymer as a Bioresponsive pDNA Delivery Vector

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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 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.

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.

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Authors and Affiliations

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

    Tsz Chung Lai & Glen S. Kwon

  2. Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, Kentucky, 40536-0082, USA

    Younsoo Bae

  3. Astellas Pharma Inc., 180, Ozumi, Yaizu-shi, Shizuoka, 425-0072, Japan

    Takayuki Yoshida

  4. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Kazunori Kataoka

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  1. Tsz Chung Lai
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  2. Younsoo Bae
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  3. Takayuki Yoshida
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  4. Kazunori Kataoka
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  5. Glen S. Kwon
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Correspondence to Glen S. Kwon.

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Lai, T.C., Bae, Y., Yoshida, T. et al. pH-Sensitive Multi-PEGylated Block Copolymer as a Bioresponsive pDNA Delivery Vector. Pharm Res 27, 2260–2273 (2010). https://doi.org/10.1007/s11095-010-0092-z

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  • DOI: https://doi.org/10.1007/s11095-010-0092-z

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