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 output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish
Pages (from-to)2260-2273
Number of pages14
JournalPharmaceutical Research
Issue number11
StatePublished - Nov 2010


  • PEG
  • non-viral gene delivery
  • pH-sensitive
  • polyplex

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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