Silver Nimesulide Complex in Bacterial Cellulose Membranes as an Innovative Therapeutic Method for Topical Treatment of Skin Squamous Cell Carcinoma

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Candido, Tuany Zambroti ; Ferraz de Paiva, Raphael Enoque ; Figueiredo, Mariana Cecchetto ; Coser, Lilian de Oliveira ; Lazarini Frajacomo, Silmara Cristina ; Abbehausen, Camilla ; Cardinalli, Izilda Aparecida ; Lustri, Wilton Rogerio ; Carvalho, Joao Ernesto ; Tasca Gois Ruiz, Ana Lucia ; Corbi, Pedro Paulo ; Passos Lima, Carmen Silvia

• Document type: Journal article
• Source: PHARMACEUTICS; v. 14, n. 2, p. 18-pg., 2022-02-01.

Abstract

Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical resection, which can cause various sequelae. Silver ions have in vitro activities over tumor cells, while nimesulide has antioxidant and anti-inflammatory activities. This study aimed to evaluate the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in a sustained release device based on bacterial cellulose membrane, named AgNMS@BCM, on topic SSCC treatment. The antiproliferative effect of AgNMS complex was evaluated in the SCC4, SCC15 and FaDu SCC lines. AgNMS complex activity on exposure of phosphatidylserine (PS) residues and multicaspase activation were evaluated on FaDu cells by flow cytometry. The AgNMS@BCM effects were evaluated in a SSCC model induced by 7,12-dimethylbenzanthracene/12-o-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) in mice. Toxicity and tumor size were evaluated throughout the study. AgNMS complex showed antiproliferative activity in SCC15 and FaDu lines in low to moderate concentrations (67.3 mu M and 107.3 mu M, respectively), and induced multicaspase activation on FaDu cells. The AgNMS@BCM did not induce toxicity and reduced tumor size up to 100%. Thus, the application of AgNMS@BCM was effective and safe in SSCC treatment in mice, and can be seen as a potential and safe agent for topic treatment of SSCC in humans. (AU)

• FAPESP's process: 16/07729-4 - Metal complex from golden, palladium and silver in the treatment of skin squamous cell carcinoma
• Grantee: Tuany Zambroti Cândido
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/12062-4 - Synthesis, characterization and studies of interaction with biomolecules of metal complexes containing biologically active ligands: a strategy in the preparation of new agents with antibacterial and antiviral activities
• Grantee: Pedro Paulo Corbi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/09833-0 - Sustainable delivery system based on biocellulose/metallic complexes containing bioactive ligands
• Grantee: Wilton Rogério Lustri
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/12719-0 - Fighting bacterial resistance: metal complexes and the metallo-beta-lactamases inhibition
• Grantee: Camilla Abbehausen
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/12590-0 - Synthesis of metal complexes with bioactive N,N or N,O-coordinating ligands for use in sustainable delivery system based on bacterial cellulose
• Grantee: Wilton Rogério Lustri
• Support Opportunities: Regular Research Grants