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: Maurizio Viale, Marta Rossi, Eleonora Russo, Michele Cilli, Anna Aprile, Aldo Profumo, Pierluigi Santi, Carla Fenoglio, Sergio Cafaggi, Mattia Rocco
• Journal: Investigational new drugs (Invest New Drugs) Vol. 33 Issue 6 Pg. 1151-61 (Dec 2015) ISSN: 1573-0646 [Electronic] United States
• PMID: 26445859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gels
• Fibrin
• Hyaluronic Acid
• Cisplatin

Topics

• Animals
• Cisplatin (administration & dosage, pharmacokinetics)
• Female
• Fibrin (administration & dosage, pharmacokinetics)
• Gels
• Humans
• Hyaluronic Acid (administration & dosage, pharmacokinetics)
• Melanoma (drug therapy, metabolism)
• Mice
• Mice, Nude
• Xenograft Model Antitumor Assays (methods)