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

Gaetano Giammona, Mariano Licciardi, Gennara Cavallaro, Christian Celia, Donatella Paolino, Massimo Fresta, Gaetano Giammona

Risultato della ricerca: Article

50 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)7340-7354
Numero di pagine15
RivistaBiomaterials
Volume31
Stato di pubblicazionePublished - 2010

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gemcitabine
Folic Acid
Copolymers
Pharmaceutical Preparations
MCF-7 Cells
Pharmacokinetics
Confocal microscopy
Phospholipids
Scintillation
Zeta potential
Cardiovascular System
Tumors
Brain
Confocal Microscopy
Antineoplastic Agents
Cells
Neoplasms
Spleen
Plasmas
Kidney

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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FOLATE-TARGETED SUPRAMOLECULAR VESICULAR AGGREGATES BASED ON POLYASPARTYL-HYDRAZIDE COPOLYMERS FOR THE SELECTIVE DELIVERY OF ANTITUMORAL DRUGS. / Giammona, Gaetano; Licciardi, Mariano; Cavallaro, Gennara; Celia, Christian; Paolino, Donatella; Fresta, Massimo; Giammona, Gaetano.

In: Biomaterials, Vol. 31, 2010, pag. 7340-7354.

Risultato della ricerca: Article

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abstract = "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.",
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T1 - FOLATE-TARGETED SUPRAMOLECULAR VESICULAR AGGREGATES BASED ON POLYASPARTYL-HYDRAZIDE COPOLYMERS FOR THE SELECTIVE DELIVERY OF ANTITUMORAL DRUGS

AU - Giammona, Gaetano

AU - Licciardi, Mariano

AU - Cavallaro, Gennara

AU - Celia, Christian

AU - Paolino, Donatella

AU - Fresta, Massimo

AU - Giammona, Gaetano

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - DRUG DELIVERY

KW - FOLATE

KW - POLYASPARTYLHYDRAZIDE

UR - http://hdl.handle.net/10447/53510

M3 - Article

VL - 31

SP - 7340

EP - 7354

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -