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The AAPS Journal

, 11:395 | Cite as

PEG-conjugated PAMAM Dendrimers Mediate Efficient Intramuscular Gene Expression

  • Rong QiEmail author
  • Yu Gao
  • Yin Tang
  • Rui-Rui He
  • Tao-Le Liu
  • Yun He
  • Sheng Sun
  • Bo-Yu Li
  • Yang-Bing Li
  • George LiuEmail author
Research Article

Abstract

Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity and unsatisfied in vivo efficacy limit their applications. In this study, to improve their characteristics as gene delivery carriers, polyethylene glycol (PEG, molecular weight 5,000) was conjugated to G5 and G6 PAMAM dendrimers (PEG-PAMAM) at three different molar ratios of 4%, 8%, and 15% (PEG to surface amine per PAMAM dendrimer molecular). Compared with unconjugated PAMAM dendrimers, PEG conjugation significantly decreased the in vitro and in vivo cytotoxicities and hemolysis of G5 and G6 dendrimers, especially at higher PEG molar ratios. Among all of the PEG-PAMAM dendrimers, 8% PEG-conjugated G5 and G6 dendrimers (G5-8% PEG, G6-8% PEG) resulted in the most efficient muscular gene expression when polyplexes were injected intramuscularly to the quadriceps of neonatal mice. Consistent with the in vivo results, these two 8% PEG-conjugated PAMAM dendrimers could also mediate the highest in vitro transfection in 293A cells. Therefore, G5-8% PEG and G6-8% PEG possess a great potential for gene delivery both in vivo and in vitro.

Key words

intramuscular gene delivery PAMAM dendrimer PEG conjugation toxicity 

Abbreviations

DMEM

Dulbecco’s modified Eagle’s medium

DMSO

dimethyl sulfoxide

FBS

fetal bovine serum

G5

PAMAM dendrimer at generation 5

G6

PAMAM dendrimer at generation 6

MW

molecular weight

PAMAM

polyamidoamine

PEI

poly(ethyleneimine)

PEG

poly(ethylene glycol)

PLL

polylysine

pEGFP

plasmid enhanced green fluorescent protein

THF

tetrahydrofuran

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 30500197).

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Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Rong Qi
    • 1
    • 3
    Email author
  • Yu Gao
    • 2
  • Yin Tang
    • 1
    • 3
  • Rui-Rui He
    • 2
  • Tao-Le Liu
    • 2
  • Yun He
    • 2
  • Sheng Sun
    • 2
  • Bo-Yu Li
    • 2
  • Yang-Bing Li
    • 2
  • George Liu
    • 1
    • 3
    Email author
  1. 1.Peking University Institute of Cardiovascular SciencesPeking University Health Science Center, Peking UniversityBeijingChina
  2. 2.School of Pharmacy, Peking University Health Science CenterPeking UniversityBeijingChina
  3. 3.Key Laboratory of Molecular Cardiovascular SciencesMinistry of EducationBeijingChina

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