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Acta Pharmaceutica Sinica ; (12): 1303-1308, 2007.
Article Dans Chinois | WPRIM | ID: wpr-268187

Résumé

Poly (2-ethylacrylic acid) (PEAA) alkylamide derivatives were synthesized for constructing pH-sensitive liposomes by partially modification of carboxylic groups of PEAA with chemical reaction. These lipid derivatives of PEAA were synthesized by partially modification of carboxylic groups of PEAA with alkylamines. The acid-sensitive polymer associated liposomes were obtained by the method of polymer self-insertion in aqueous solutions through inserting hydrophobic lipid anchors of the polymer PEAA derivatives into the outer layer of vesicles. Factor effects on polymer insertion into liposomes were evaluated and the pH-sensitivity of the polymer associated liposomes was studied by calcein release assay. The PEAA-assoeiated-liposomes were prepared successfully by the methods of self-insertion. The PEAA-associated-liposomes are shown to be stable at neutral pH. (1) There was no correlate of anchor density of PEAA with length of the alkyl chain, but was positively correlated with the degree of PEAA modification. (2) Polymer insertion increased with initial ratio of polymer to lipid. (3) Unerting hydrophobic lipidr acidic conditions the associated polymer induces membrane disruption and fusion. (4) The PEAA-associated-liposomes shown pH-sensitive drug release property under acidic conditions. The anchored-poly (ethylacrylic acid) lipid derivatives can be useful in developing a potential pH sensitive drug delivery system.


Sujets)
Animaux , Acrylates , Pharmacocinétique , Cellules COS , Chlorocebus aethiops , Systèmes de délivrance de médicaments , Méthodes , Fluorescéines , Métabolisme , Concentration en ions d'hydrogène , Liposomes , Chimie , Pharmacocinétique , Taille de particule , Amides gras polyinsaturés N-alkylés , Pharmacocinétique
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