Fabio Sonvico1,2, Stefano Barbieri1,2, Paolo Colombo2,3, Claudio Mucchino4, Elisabetta Barocelli2, Anna Maria Cantoni5, Andrea Cavazzoni6, Pier Giorgio Petronini6, Michele Rusca7, Paolo Carbognani7, Luca Ampollini7. 1. Biopharmanet-TEC, University of Parma, Parma, Italy. 2. Department of Food and Drug, University of Parma, Parma, Italy. 3. Plumestars s.r.l., Via Inzani 1, Parma, Italy. 4. Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy. 5. Department of Veterinary Sciences, University of Parma, Parma, Italy. 6. Department of Medicine and Surgery, University of Parma, Parma, Italy. 7. Thoracic Surgery, Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy.
Abstract
BACKGROUND: Malignant mesothelioma is an invasive neoplasm arising from mesothelial surfaces of the pleural and peritoneal cavities. Mesothelioma treatment is unsatisfactory and recurrence is common. Here an innovative locoregional treatment for malignant pleural mesothelioma is presented. METHODS: Chitosan- and hyaluronate-based films were loaded with 0.5% and 4% w/w cisplatin and were studied for their physicochemical, mechanical and drug release characteristics. The performance of the drug delivery systems was assessed in vitro on A549 cells and on an orthotopic model of MPM recurrence in rats. RESULTS: Polysaccharide films produced were thin, flexible and resistant. Cisplatin was completely released from hyaluronic acid films within 96 hours, while drug release was found to be much more prolonged with chitosan films. The drug released from hyaluronate films was effective against A549 cell line, while for chitosan films the release was too slow to produce cytotoxicity. Similarly, cisplatin-loaded chitosan films in vivo released minimal quantities of cisplatin and induced inflammation and foreign body reaction. Cisplatin-loaded hyaluronate acid films on the contrary were able to prevent tumor recurrence. The cisplatin-loaded hyaluronate films provided higher Cmax and AUC compared to a solution of cisplatin administered intrapleurally, but did not show any sign of treatment related toxicity. CONCLUSIONS: Hyaluronate-based films appear as an optimal platform for the development of drug delivery systems suitable for the loco-regional post-surgical treatment of lung malignancies.
BACKGROUND: Malignant mesothelioma is an invasive neoplasm arising from mesothelial surfaces of the pleural and peritoneal cavities. Mesothelioma treatment is unsatisfactory and recurrence is common. Here an innovative locoregional treatment for malignant pleural mesothelioma is presented. METHODS: Chitosan- and hyaluronate-based films were loaded with 0.5% and 4% w/w cisplatin and were studied for their physicochemical, mechanical and drug release characteristics. The performance of the drug delivery systems was assessed in vitro on A549 cells and on an orthotopic model of MPM recurrence in rats. RESULTS: Polysaccharide films produced were thin, flexible and resistant. Cisplatin was completely released from hyaluronic acid films within 96 hours, while drug release was found to be much more prolonged with chitosan films. The drug released from hyaluronate films was effective against A549 cell line, while for chitosan films the release was too slow to produce cytotoxicity. Similarly, cisplatin-loaded chitosan films in vivo released minimal quantities of cisplatin and induced inflammation and foreign body reaction. Cisplatin-loaded hyaluronate acid films on the contrary were able to prevent tumor recurrence. The cisplatin-loaded hyaluronate films provided higher Cmax and AUC compared to a solution of cisplatin administered intrapleurally, but did not show any sign of treatment related toxicity. CONCLUSIONS: Hyaluronate-based films appear as an optimal platform for the development of drug delivery systems suitable for the loco-regional post-surgical treatment of lung malignancies.
Entities:
Keywords:
Cisplatin; hyaluronate; loco-regional; mesothelioma; thin film
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