title: Folate-targeted supramolecular vesicular aggregates based on polyaspartyl-hydrazide copolymers for the selective delivery of antitumoral drugs.
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, flow cytometry analysis and beta-scintillation highlighted that FT-SVAs were 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. SVAs were accumulated mainly in the lungs, spleen and kidneys, while FT-SVAs were 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.
authors.affiliation: Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Licciardi
authors.forename: Donatella
authors.initials: D
authors.lastname: Paolino
authors.forename: Christian
authors.initials: C
authors.lastname: Celia
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
authors.forename: Gennara
authors.initials: G
authors.lastname: Cavallaro
authors.forename: Massimo
authors.initials: M
authors.lastname: Fresta
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001386:Azides / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008422:Materials Testing; D018613:Microscopy, Confocal; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D014018:Tissue Distribution; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D001386:Azides; D001672:Biocompatible Materials; D004337:Drug Carriers; D010455:Peptides; D011108:Polymers; D003841:Deoxycytidine; C017645:polyaspartate; D005492:Folic Acid; D000093542:Gemcitabine