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  • Title: Enzyme-induced shedding of a poly(amino acid)-coating triggers contents release from dioleoyl phosphatidylethanolamine liposomes.
    Author: Romberg B, Flesch FM, Hennink WE, Storm G.
    Journal: Int J Pharm; 2008 May 01; 355(1-2):108-13. PubMed ID: 18206323.
    Abstract:
    The enzymatically degradable poly(amino acid)-lipid conjugate poly(hydroxyethyl l-glutamine)-N-succinyl-dioctadecylamine (PHEG-DODASuc) has been shown to effectively prolong liposome circulation times. In this paper, we investigated whether PHEG-DODASuc can stabilize liposomes composed of the fusogenic, non-bilayer-forming lipid dioleoyl phosphatidylethanolamine (DOPE). Moreover, we evaluated the release of an entrapped compound after enzyme-induced shedding of the PHEG-coating, interbilayer contact and membrane destabilizing phase changes. Contents release was monitored using the fluorescent model compound calcein. Liposome destabilization and lipid mixing was studied by dynamic light scattering (DLS), fluorescence resonance energy transfer (FRET) and cryogenic-temperature transmission electron microscopy (cryo-TEM). It was shown that PHEG-DODASuc is able to stabilize DOPE-based liposomes and that contents release can be triggered by shedding of the PHEG-coating.
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