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  • Title: Envelope-type lipid nanoparticles incorporating a short PEG-lipid conjugate for improved control of intracellular trafficking and transgene transcription.
    Author: Masuda T, Akita H, Niikura K, Nishio T, Ukawa M, Enoto K, Danev R, Nagayama K, Ijiro K, Harashima H.
    Journal: Biomaterials; 2009 Sep; 30(27):4806-14. PubMed ID: 19520424.
    Abstract:
    Lipid envelope-type nanoparticles are promising carriers for gene delivery. The modification of liposomes with polyethyleneglycol (PEG) can often be useful in liposomal formation and pharmacokinetics. However, there is a dilemma concerning the use of PEG because of its poor intracellular trafficking properties. To overcome this problem, in the present study, we report on a strategy for improving the intracellular trafficking of PEG-modified lipid particles by incorporating a short PEG lipid. The findings presented here show that the incorporation of tetra(ethylene)glycol (TEG)-conjugated cholesterol into a liposome composition is useful in controlling the number of lipid envelopes, resulting in an improvement in particle uniformity with a reduced particle size. The TEG-modified lipid particles were found to enhance transfection activity by more than 100-fold. This increase is attributed to an enhancement of cellular uptake, and nuclear transcription by improving intracellular decoating. Moreover, the use of a various short PEG lipids in lipid particle formation showed a clear threshold polymerization degree (less or equal 25: PEG1100), for achieving stimulated transfection activity. Collectively, the use of short PEG lipid promises to be useful in developing an efficient non-viral gene vector.
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