Pharmaceutical Research

, Volume 27, Issue 11, pp 2260–2273

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

  • Tsz Chung Lai
  • Younsoo Bae
  • Takayuki Yoshida
  • Kazunori Kataoka
  • Glen S. Kwon
Research Paper
  • 304 Downloads

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.

KEY WORDS

non-viral gene delivery PEG pH-sensitive polyplex 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Tsz Chung Lai
    • 1
  • Younsoo Bae
    • 2
  • Takayuki Yoshida
    • 3
  • Kazunori Kataoka
    • 4
  • Glen S. Kwon
    • 1
  1. 1.Division of Pharmaceutical Sciences, School of PharmacyUniversity of Wisconsin – MadisonMadisonUSA
  2. 2.Division of Pharmaceutical Sciences, College of PharmacyUniversity of KentuckyLexingtonUSA
  3. 3.Astellas Pharma Inc.ShizuokaJapan
  4. 4.Department of Materials Engineering, Graduate School of EngineeringThe University of TokyoTokyoJapan

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