TY - JOUR
T1 - PH-sensitive multi-PEGylated block copolymer as a bioresponsive pDNA delivery vector
AU - Lai, Tsz Chung
AU - Bae, Younsoo
AU - Yoshida, Takayuki
AU - Kataoka, Kazunori
AU - Kwon, Glen S.
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - PEG
KW - non-viral gene delivery
KW - pH-sensitive
KW - polyplex
UR - https://www.scopus.com/pages/publications/78549291065
UR - https://www.scopus.com/pages/publications/78549291065#tab=citedBy
U2 - 10.1007/s11095-010-0092-z
DO - 10.1007/s11095-010-0092-z
M3 - Article
C2 - 20300803
AN - SCOPUS:78549291065
SN - 0724-8741
VL - 27
SP - 2260
EP - 2273
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 11
ER -