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Anionic polyethyleneglycol lipids added to cationic lipoplexes increase their plasmatic circulation time
Céline Nicolazzi1, Nathalie Mignet, Natalia de la Figuera
1CNRS-UMR7001/ENSCP/Gencell S A, Aventis Pharma, 13 Quai Jules Guesdes 94403, Vitry/Seine, France.
Summary
Novel anionic shielding of cationic liposomes improves DNA delivery. This approach enhances colloidal stability and reduces non-specific interactions, paving the way for effective in vivo gene therapy.
Area of Science:
- Biotechnology
- Nanomedicine
- Gene Therapy
Background:
- Cationic liposomes are effective DNA delivery agents in vitro.
- In vivo, cationic liposomes interact with blood components, limiting their therapeutic efficacy.
- Polyethyleneglycol (PEG) shielding has shown limited success for systemic administration.
Purpose of the Study:
- To develop an improved shielding strategy for cationic liposomes.
- To enhance the in vivo performance of DNA-compacting liposomes.
- To overcome limitations of current PEG shielding for gene delivery.
Main Methods:
- Insertion of anionic functions between the lipid and PEG layers of liposomes.
- Evaluation of lipoplex charge (zeta potential) and colloidal stability in serum.
- Assessment of in vivo gene transfection efficiency in lung and tumor tissues.
Main Results:
- Anionic shielding decreased lipoplex peripheral charge (zeta potential).
- Shielded liposomes exhibited enhanced colloidal stability in the presence of serum.
- Lung transfection was reduced, while tumor transfection remained unchanged.
Conclusions:
- Anionic shielding is a promising strategy to improve cationic liposome performance for gene delivery.
- This approach enhances stability and reduces non-specific interactions.
- Combining anionic shielding with active targeting may enable effective tumor gene delivery.