Supramolecular vesicular aggregates (SVAs) have the advantage of combining the safe and biocompatible properties 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, folate moieties were chemically conjugated to PAHy copolymers. Physicochemical properties (mean sizes, polydispersity index 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 against two cancer cell lines, i.e. MCF-7 cells which over-express the folate receptor and the BxPC-3 cells, which do not over-express this receptor. Gemcitabine-loaded FT-SVAs showed a significantly (p < 0.001) greater and more specific in vitro anticancer activity with respect to both the free drug and the drug-loaded conventional liposomes or untargeted SVAs. Confocal microscopy, flowcytometry analysis and b-scintillation highlighted that FT-SVAswere able to interact with MCF-7 cells after just 3 h and to increase the amount internalization in cells over-expressing the folate receptor. The in vivo biodistribution and pharmacokinetic experiments showed that gemcitabine-loaded SVAs and FT-SVAs were removed from the circulatory system at a slower rate 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 and encourage the use of folate as a targeting agent in anticancer therapy.

LICCIARDI, M., PAOLINO, D., CELIA, C., GIAMMONA, G., CAVALLARO, G., FRESTA, M. (2010). FOLATE-TARGETED SUPRAMOLECULAR VESICULAR AGGREGATES BASED ON POLYASPARTYL-HYDRAZIDE COPOLYMERS FOR THE SELECTIVE DELIVERY OF ANTITUMORAL DRUGS. BIOMATERIALS, 31, 7340-7354 [10.10016/J.biomaterials 2010.05.060].

FOLATE-TARGETED SUPRAMOLECULAR VESICULAR AGGREGATES BASED ON POLYASPARTYL-HYDRAZIDE COPOLYMERS FOR THE SELECTIVE DELIVERY OF ANTITUMORAL DRUGS

LICCIARDI, Mariano;GIAMMONA, Gaetano;CAVALLARO, Gennara;
2010-01-01

Abstract

Supramolecular vesicular aggregates (SVAs) have the advantage of combining the safe and biocompatible properties 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, folate moieties were chemically conjugated to PAHy copolymers. Physicochemical properties (mean sizes, polydispersity index 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 against two cancer cell lines, i.e. MCF-7 cells which over-express the folate receptor and the BxPC-3 cells, which do not over-express this receptor. Gemcitabine-loaded FT-SVAs showed a significantly (p < 0.001) greater and more specific in vitro anticancer activity with respect to both the free drug and the drug-loaded conventional liposomes or untargeted SVAs. Confocal microscopy, flowcytometry analysis and b-scintillation highlighted that FT-SVAswere able to interact with MCF-7 cells after just 3 h and to increase the amount internalization in cells over-expressing the folate receptor. The in vivo biodistribution and pharmacokinetic experiments showed that gemcitabine-loaded SVAs and FT-SVAs were removed from the circulatory system at a slower rate 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 and encourage the use of folate as a targeting agent in anticancer therapy.
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
LICCIARDI, M., PAOLINO, D., CELIA, C., GIAMMONA, G., CAVALLARO, G., FRESTA, M. (2010). FOLATE-TARGETED SUPRAMOLECULAR VESICULAR AGGREGATES BASED ON POLYASPARTYL-HYDRAZIDE COPOLYMERS FOR THE SELECTIVE DELIVERY OF ANTITUMORAL DRUGS. BIOMATERIALS, 31, 7340-7354 [10.10016/J.biomaterials 2010.05.060].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/53510
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