title: Ultradeformable liposomes as multidrug carrier of resveratrol and 5-fluorouracil for their topical delivery.
abstract: Ultradeformable liposomes represent useful formulations able to increase the skin permeation of drug compounds. In this study, resveratrol- and 5-fluorouracil-loaded ultradeformable liposomes were investigated for the potential treatment of non-melanoma skin cancer. The in vitro anticancer activity of ultradeformable liposomes was tested on human skin cancer cells through viability-, cell cycle- and apoptosis-analysis. Furthermore, we tested the percutaneous permeation of ultradeformable liposomes using human stratum corneum and viable epidermis. The co-encapsulation of resveratrol and 5-fluorouracil (multi-drug carrier) in ultradeformable liposomes improved their anticancer activity on skin cancer cells as compared to both the free drug form and the single entrapped agents. These multi-drug ultradeformable liposomes arrest cell proliferation in G1/S, thus modifying the action of 5-fluorouracil and increasing the activity of resveratrol. This effect might depend on the ultradeformable liposomes, which may accumulate in deeper skin layers, thus generating a cutaneous depot from which resveratrol and 5-fluorouracil are gradually released. Resveratrol and 5-fluorouracil co-loaded ultradeformable liposomes could be a new nanomedicine for the treatment of squamous cell carcinoma, i.e., actinic keratosis, Bowen's disease, and keratoacanthoma.
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy; IRC FSH - Interregional Research Center for Food Safety & Health, University of Catanzaro "Magna Græcia", Campus Universitario "S. Venuta" - Building of BioSciences, Viale S. Venuta, I-88100 Germaneto, Catanzaro, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Cosco
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy; IRC FSH - Interregional Research Center for Food Safety & Health, University of Catanzaro "Magna Græcia", Campus Universitario "S. Venuta" - Building of BioSciences, Viale S. Venuta, I-88100 Germaneto, Catanzaro, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Paolino
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Maiuolo
authors.affiliation: Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, I-66100 Chieti, Italy.
authors.forename: Luisa Di
authors.initials: LD
authors.lastname: Marzio
authors.affiliation: Department of Drug Chemistry and Technologies, University "Sapienza" of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Carafa
authors.affiliation: Department of Drug Science and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Cinzia A
authors.initials: CA
authors.lastname: Ventura
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy; IRC FSH - Interregional Research Center for Food Safety & Health, University of Catanzaro "Magna Græcia", Campus Universitario "S. Venuta" - Building of BioSciences, Viale S. Venuta, I-88100 Germaneto, Catanzaro, Italy. Electronic address: fresta@unicz.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fresta
mesh_terms: D000279:Administration, Cutaneous; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D000077185:Resveratrol; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012878:Skin Neoplasms / Q000188:drug therapy; D013267:Stilbenes / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D013267:Stilbenes; D000077185:Resveratrol; D005472:Fluorouracil
keywords: Multi-drug colloidal carriers; Skin cancer; Skin delivery; Supramolecular therapeutics; Ultradeformable liposomes