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Silver Nimesulide Complex in Bacterial Cellulose Membranes as an Innovative Therapeutic Method for Topical Treatment
Tuany Zambroti Candido1, Raphael Enoque Ferraz de Paiva2, Mariana Cecchetto Figueiredo3
1Department of Anesthesiology, Oncology and Radiology, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas 13083-887, SP, Brazil.
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 µM and 107.3 µM, 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.
Insights
A novel silver(I) complex with nimesulide (AgNMS) in a bacterial cellulose membrane (AgNMS@BCM) effectively treated skin squamous cell carcinoma (SSCC) in mice. This topical treatment demonstrated significant tumor reduction without toxicity, showing promise for human SSCC therapy.
Area of Science:
- Oncology
- Dermatology
- Materials Science
Background:
- Skin squamous cell carcinoma (SSCC) development is influenced by oxidative stress and inflammation.
- Current SSCC treatment, primarily surgical resection, can lead to adverse sequelae.
- Silver ions exhibit anti-tumor properties, while nimesulide possesses antioxidant and anti-inflammatory effects.
Purpose of the Study:
- To evaluate the efficacy and safety of a silver(I) complex with nimesulide (AgNMS) incorporated into a bacterial cellulose membrane (AgNMS@BCM) for topical SSCC treatment.
Main Methods:
- In vitro antiproliferative and apoptosis assays (phosphatidylserine exposure, multicaspase activation) of AgNMS complex on SSCC cell lines (SCC4, SCC15, FaDu).
- In vivo evaluation of AgNMS@BCM in a DMBA/TPA-induced SSCC mouse model.
- Assessment of toxicity and tumor size reduction in the animal model.
Main Results:
- AgNMS complex demonstrated antiproliferative activity against SCC15 and FaDu cell lines.
- AgNMS complex induced multicaspase activation in FaDu cells, indicating apoptosis.
- AgNMS@BCM treatment resulted in up to 100% tumor size reduction in the SSCC mouse model without observable toxicity.
Conclusions:
- The AgNMS@BCM formulation is an effective and safe topical treatment for SSCC in a preclinical mouse model.
- This novel AgNMS@BCM holds potential as a safe and effective agent for the topical treatment of human SSCC.
