Silk fibroin membranes for controlled release of drugs: incorporation method, chemical and morphological characteristics

Abstract

Event Abstract Back to Event Silk fibroin membranes for controlled release of drugs: incorporation method, chemical and morphological characteristics Bruno Tomoda1, Marisa Beppu1, Mariana Agostini De Moraes1, 2 and Giovana M. Genevro1 1 University of Campinas, School of Chemical Engineering, Brazil 2 Federal University of São Paulo, Department of Exact and Earth Science, Brazil Introduction: Silk fibroin (SF) is a natural polymer present in the cocoons of silkworms, which has been studied in the biomaterials area[1],[2]. SF membranes have good water vapor and oxygen permeability, blood compatibility and improve collagen formation and fibroblast proliferation[3], which makes them a promising material for application as wound dressings. The aim of this work is to study the incorporation of a model drug in dense membranes of silk fibroin and evaluate the drug release kinetics, aiming application as high performance wound dressing. Materials and Methods: Silk fibroin solution was prepared from cocoons of Bombyx mori silkworm (provided by Bratac, Bastos/ SP/Brazil) according to previously published procedure[4],[5]. SF membranes were prepared by casting SF aqueous solution. Diclofenac sodium (DS), an anti-inflammatory and analgesic drug used worldwide, was chosen as drug model. Two different methods for DS solution (10 mg/mL) incorporation were studied: 1) Incorporation of DS solution directly in SF solution, prior to membrane preparation; 2) Incorporation of DS on SF membrane by adsorption. The membranes were characterized by FTIR and SEM-EDS. Drug release was performed in phosphate buffer saline (PBS) and in water. Samples were collected at fixed time intervals and analyzed by UV/vis spectroscopy, at 276 nm. Results and Discussion: FTIR results (Figure 1), show that pure SF membranes undergo conformation transition from random coil/α-helix to stable β-sheets when ethanol post-treatment is performed[5]. Interestingly, when DS solution is incorporated in SF solution, prior to membrane preparation, the same conformational transition is observed. For the incorporation method by adsorption, ethanol post-treatment of SF membranes was necessary, to avoid membrane degradation prior to the DS incorporation. Thus, ethanol post-treatment is a step of production that can be eliminated when DS solution incorporation method is performed. SEM micrographs (Figure 2) revealed that SF membranes prepared by DS incorporation in SF solution present globular structures of regular size and shape and uniformly distributed within the membranes. The process of globule formation was spontaneous and allowed the encapsulation of DS inside the globules, as confirmed by EDS mapping. On the contrary, when the adsorption method was performed, DS was found just on the surface of the membrane. Drug release results (Figure 3) demonstrate that DS has a faster initial release in water than in PBS. Moreover, DS was completely released in water, whereas in PBS just 70% of DS was released. This difference is related to DS solubility, which is higher in water than in PBS. The release equilibrium was reached after 100 minutes for both media. Conclusion: The method of DS solution incorporation directly in SF solution, prior to membrane preparation, was the most promising one. By this method SF underwent conformation transition to a more stable form, avoiding additional post-treatments. Furthermore, SF self-assembled into globular structures containing the DS encapsulated, which is usually desired for controlled release applications. SF membranes showed a fast initial release and equilibrium was reached after approximately 100 minutes of release. These results revealed an excellent drug incorporation method and confirm the potential application of SF membranes in wound dressings; however, further studies should be carried out in order to obtain a slow release kinetics. CNPq; FAPESP