Sterically stabilized BGTC-based lipoplexes: structural features and gene transfection into the mouse airways in vivo
✍ Scribed by Bruno Pitard; Noufissa Oudrhiri; Olivier Lambert; Eric Vivien; Christophe Masson; Barbara Wetzer; Michelle Hauchecorne; Daniel Scherman; Jean-Louis Rigaud; Jean-Pierre Vigneron; Jean-Marie Lehn; Pierre Lehn
- Book ID
- 102341785
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 343 KB
- Volume
- 3
- Category
- Article
- ISSN
- 1099-498X
- DOI
- 10.1002/jgm.211
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✦ Synopsis
Background:
Colloidal stability of lipid/dna aggregates is a major requirement for cationic lipid-mediated transfection which is particularly difficult to fulfil at the high dna concentrations used for in vivo gene delivery. thus, we have investigated the potential of poly(ethyleneglycol) (peg) conjugates for steric stabilization of lipoplexes formed by bis(guanidinium)-tren-cholesterol/dioleoyl phosphatidylethanolamine (bgtc/dope) liposomes, a class of cationic liposomes we have developed over the past few years.
Methods and results:
We demonstrate that adequate lipophilic peg derivatives can stabilize bgtc/dope lipoplexes formed at high dna concentration. we also report the results of cryotransmission electron microscopy studies indicating that peg-stabilized lipoplexes form dna-coated structures which assemble into clusters exhibiting various complex morphologies. finally, we report data from in vivo transfection experiments suggesting that peg-mediated colloidal stabilization of concentrated lipoplex solutions may allow enhanced transfection of the mouse airways via intranasal administration.
Conclusion:
Our results represent an important step towards the design of multimodular bgtc-based systems for improved in vivo gene transfection.