title: Fibrin gels loaded with cisplatin and cisplatin-hyaluronate complexes tested in a subcutaneous human melanoma model.
abstract: Fibrin gels are attractive biomaterials for local delivery of a variety of agents, from drugs to proteins. Similarly, polymer-anticancer-drug conjugates and nanoparticles are emerging as potential candidates for cancer treatment. Combining these different approaches, we have studied the efficacy of fibrin gels loaded with cisplatin (DDP) and a complex of DDP with hyaluronate (DDP-HA) for tumor growth inhibition in a melanoma model. Loaded gels prepared at relatively high fibrinogen concentration (22 mg/ml) showed good in vitro antiproliferative activities, prolonged release of the anticancer drug, and a long persistence (10-15 days) in vivo when implanted subcutaneously (sc) in immunodeficient mice. Gels loaded with DDP or DDP-HA containing 1/3 or even 1/6 of their systemic dose (6 mg/kg) and positioned under the tumor mass in mice bearing a sc human SK-Mel-28 tumor showed an antitumor activity better than that of the original parent compound given intraperitoneally (ip). Moreover, in an additional experiment in vivo, fibrin gels loaded with N-trimethyl chitosan-based nanoparticles containing a DDP-HA complex were assayed, resulting in a further 8 % improvement of anticancer activity, with lesser adverse systemic toxic effects. Taken together, these results suggest that the combination of fibrin gels and drugs complexed with suitable macromolecules holds great promise for loco-regional anticancer therapy of melanoma and other surgically removable cancer types.
authors.affiliation: U.O.C. Bioterapie, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132, Genova, Italy. maurizio.viale@hsanmartino.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viale
authors.affiliation: U.O.C. Bioterapie, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132, Genova, Italy.|S.C. Farmacia Interna, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Dipartimento di Farmacia, Università di Genova, Viale Cembrano 4, 16148, Genova, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Russo
authors.affiliation: U.O.S. Animal Facility, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Cilli
authors.affiliation: U.O.S. Biopolimeri e Proteomica, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Aprile
authors.affiliation: U.O.S. Biopolimeri e Proteomica, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Profumo
authors.affiliation: U.O.C. Plastic and Reconstructive Surgery, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Santi
authors.affiliation: Dipartimento di Biologia e Biotecnologie, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Fenoglio
authors.affiliation: Dipartimento di Farmacia, Università di Genova, Viale Cembrano 4, 16148, Genova, Italy. cafaggi@difar.unige.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Cafaggi
authors.affiliation: U.O.S. Biopolimeri e Proteomica, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Rocco
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005337:Fibrin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005782:Gels; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D005782:Gels; D005337:Fibrin; D006820:Hyaluronic Acid; D002945:Cisplatin
keywords: Cisplatin; Cisplatin-hyaluronate complex; Fibrin gel; Local treatment; Melanoma; Nanoparticles