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Open AccessArticle

Orphan Designation and Cisplatin/Hyaluronan Complex in an Intracavitary Film for Malignant Mesothelioma

1
Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy
2
Food and Drug Department, University of Parma, Parco Area delle Scienze 27A, 43124 Parma, Italy
3
PlumeStars srl, c/o Food & Drug Department, Parco Area delle Scienze 27A, 43124 Parma, Italy
4
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Paola Minghetti
Pharmaceutics 2021, 13(3), 362; https://doi.org/10.3390/pharmaceutics13030362
Received: 19 February 2021 / Revised: 2 March 2021 / Accepted: 4 March 2021 / Published: 9 March 2021
Pleural mesothelioma is a lung diffuse tumor, whose complete resection is unlikely. Consequently, metastases reappear where the primary tumor was removed. This paper illustrates the orphan medicine designation procedure of an intracavitary cisplatin film and related pharmaceutical development aspects requested by the European Medicines Agency (EMA) in its Scientific Advice. Since cisplatin pharmacokinetics from the implanted film in sheep resulted substantially modified compared to intravenous administration, the formation of a cisplatin/hyaluronan complex had been hypothesized. Here, the interaction between sodium hyaluronate (NaHA) and cisplatin (CisPt) was demonstrated. Size exclusion chromatography qualitatively evidenced the complex in the film-forming mixture, only showing the NaHA peak. Atomic absorption spectroscopy of the corresponding fraction revealed platinum, confirming the interaction. Reverse phase HPLC quantified about 5% free cisplatin in the film-forming mixture, indirectly meaning that 95% was complexed. Finally, a study of CisPt release from the film assessed how CisPt/NaHA complex affected drug availability. In water, a medium without chloride ions, there was no release and the film remained intact for 48 h and longer, whereas the placebo film dissolved in 15 min. In 0.9% NaCl medium, the film became more soluble, dissolving within 3–4 h. However, cisplatin release was still controlled by the existing complex in solution until chloride ions displaced it. While the film modified its dissolution with aging, CisPt release remained unaffected (90% released in 48 h). View Full-Text
Keywords: cisplatin; sodium hyaluronate; complex; film; intracavitary; intrapleural; mesothelioma; orphan designation cisplatin; sodium hyaluronate; complex; film; intracavitary; intrapleural; mesothelioma; orphan designation
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MDPI and ACS Style

Banella, S.; Quarta, E.; Colombo, P.; Sonvico, F.; Pagnoni, A.; Bortolotti, F.; Colombo, G. Orphan Designation and Cisplatin/Hyaluronan Complex in an Intracavitary Film for Malignant Mesothelioma. Pharmaceutics 2021, 13, 362. https://doi.org/10.3390/pharmaceutics13030362

AMA Style

Banella S, Quarta E, Colombo P, Sonvico F, Pagnoni A, Bortolotti F, Colombo G. Orphan Designation and Cisplatin/Hyaluronan Complex in an Intracavitary Film for Malignant Mesothelioma. Pharmaceutics. 2021; 13(3):362. https://doi.org/10.3390/pharmaceutics13030362

Chicago/Turabian Style

Banella, Sabrina; Quarta, Eride; Colombo, Paolo; Sonvico, Fabio; Pagnoni, Antonella; Bortolotti, Fabrizio; Colombo, Gaia. 2021. "Orphan Designation and Cisplatin/Hyaluronan Complex in an Intracavitary Film for Malignant Mesothelioma" Pharmaceutics 13, no. 3: 362. https://doi.org/10.3390/pharmaceutics13030362

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