RELEASE PROFILE OF SILVER FROM A BACTERIAL CELLULOSE MEMBRANE LOADED WITH A SILVER-NIMESULIDE COMPLEX

Abstract

Introduction

Topical drug delivery systems have been developed with the aim of promoting localized pharmacological action in a prolonged and safe manner. Among the different strategies employed, bacterial cellulose membranes (BCM) stand out due to their ability to act as biocuratives applied directly on to cutaneous lesions. We previously evaluated the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in devices based on BCM, named AgNMS@BCM, on topic skin squamous cell carcinoma (SSCC) treatment in pre-clinical experiments. The AgNMS showed antiproliferative effects in the SCC4, SCC15 and FaDu SCC lines, and the AgNMS@BCM induced reduction of tumor size up to 75%, without toxicity, in a skin carcinogenesis model in mice. Facing these exciting results, we are testing the efficacy and safety of AgNMS@BCM in humans in a phase I/II study. From a regulatory perspective, demonstrating the release of active compounds incorporated into a BCM is a fundamental requirement of health authorities, which makes specific release assays essential for the characterization of the drug release profile. Within this context, the objective of the present study was defined.

Objective

This study aimed to evaluate the silver(I) release profile from BCM impregnated with a AgNMS complex.

Materials and Methods

Release experiments were performed using Franz diffusion cells, employing BCM loaded with the AgNMS complex at a concentration of 0.5 mg/cm², with phosphate-buffered saline (PBS) 1% used as the receptor medium. Samples from the receptor medium were collected (300 µl) at predefined time intervals (0, 1, 4, 8, 12, and 24 h) and subsequently subjected to silver(I) quantification by inductively coupled plasma mass spectrometry (ICP-MS), with each sample analyzed in triplicate. In addition, the quantification of NMS by UV–Vis spectrophotometry, as well as morphological analyses by scanning electron microscopy, are currently underway.

Results

The results were expressed as mean ± standard deviation as a function of time, with the following values observed: T0 (6.82 ± 2.29), T1 – 1h (89.22 ± 23.04), T2 – 4h (248.95 ± 65.84), T3 – 8h (303.29 ± 56.31), T4 – 12h (454.76 ± 79.45), and T5 – 24h (455.78 ± 45.56). Overall, the data demonstrated that the BCM promotes a gradual release of the metallic complex up to 8h, followed by a release plateau at 12h and 24h.

Conclusion

Therefore, it can be concluded that BCM represents a promising sustained-release system for the AgNMS complex, meeting regulatory requirements for drug release characterization. This behavior supports the maintenance of the biocurative throughout the treatment period and reinforces the translational potential of AgNMS@BCM for clinical application in patients with SSCC.