Local delivery for cancer chemioterapy of a cisplatin-hyaluronic acid complex entrapped in fibrin gels

Surgical removal of cancer lesions is often the elective treatment, but complete eradication cannot always be achieved, increasing the risk of primary tumour recurrence. Systemic chemotherapy is therefore mandatory, but drug uptake at the required site could be problematic, and its side effects can be severe. Local delivery of antineoplastic agents would therefore be highly desirable. Fibrin is an attractive vehicle for local delivery of a variety of agents, from drugs to proteins. Similarly, polymer-anticancer-drug conjugates are emerging as potential candidates for cancer treatment and the application of personalized therapies. Joining these different approaches, we have employed fibrin gels loaded with a cisplatin-hyaluronic acid complex that previously demonstrated a good antitumour activity. Our 22 mg/ml gels prepared in the presence of 0.25 NIH units thrombin/mg fibrinogen and 2.5 mM CaCl2 showed good in vitro antiproliferative activities, prolonged release of the anticancer drug, and a long permanence in vivo (10-15 days) when implanted subcutaneously. When charged with the complex containing 1/6 of the ip dose of cisplatin (6 mg/Kg) administered to treat mice bearing a sc SK-Mel-28 tumour, our gels positioned under the tumour mass showed an antitumour activity similar to that of the original parent compound given ip. At the dose of 2 mg/Kg, the effect of our gels was even better than that observed with 6 mg/Kg ip cisplatin. Our data show that fibrin gels represent a good tool to deliver anticancer drugs complexed with suitable macromolecules and in a loco-regional way.