Supramolecular vesicular aggregates (SVAs) have the advantage of combining the safe and biocompatibleproperties of colloidal vesicular carriers based on phospholipids with those of polymeric materials, i.e.polyaspartyl-hydrazide (PAHy) copolymers. To provide SVAs with a certain tumour selectivity, folatemoieties were chemically conjugated to PAHy copolymers. Physicochemical properties (mean sizes, polydispersityindex and zeta potential) of folate-targeted SVAs (FT-SVAs) loaded with gemcitabine were evaluated.The antiproliferative and anticancer activity of gemcitabine-loaded FT-SVAs was evaluated againsttwo cancer cell lines, i.e. MCF-7 cells which over-express the folate receptor and the BxPC-3 cells, which donot over-express this receptor. Gemcitabine-loaded FT-SVAs showed a significantly (p < 0.001) greater andmore specific in vitro anticancer activity with respect to both the free drug and the drug-loaded conventionalliposomes or untargeted SVAs. Confocal microscopy, flowcytometry analysis and b-scintillation highlightedthat FT-SVAswere able to interact with MCF-7 cells after just 3 h and to increase the amount internalizationin cells over-expressing the folate receptor. The in vivo biodistribution and pharmacokinetic experimentsshowed that gemcitabine-loaded SVAs and FT-SVAs were removed from the circulatory system at a slowerrate than the native drug and a prolonged gemcitabine plasma concentration was observed for up to 16 h.SVAswere accumulated mainly in the lungs, spleen and kidneys, while FT-SVAswere also up taken by brain.These interesting and stimulating results suggest the existence of a possible in vivo application of SVAs andencourage the use of folate as a targeting agent in anticancer therapy.
|Numero di pagine||15|
|Stato di pubblicazione||Published - 2010|
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