Abstract

In this study, we propose a novel model of multi-layered, silk-based films for sustained and controlled release of multiple drugs for up to 25 days (600 h), with a prolonged tail-release phase extending to 45 days (1080 h), for biomedical applications. The compounds tested included ciprofloxacin (CIP, antibiotic) and dexamethasone (DEX, steroid) widely used in therapeutics formulations for the treatment of ear diseases like chronic otitis media. Using a layer-by-layer (LbL) assembly approach, sodium deoxycholate was also incorporated as a pH-sensitive, charge-interfacing agent between silk layers comprising of CIP or DEX, which proved critical in modulating interlayer interactions, enhancing drug loading, and enabling tunable release profiles of multiple drugs with varying chemical properties. In vitro drug release studies demonstrated that CIP was released more rapidly than DEX under physiological conditions and depending on the changes in the environmental pH, one drug will be selectively released prior to the other, which can be useful in applications involving treatment of bacterial infections. Incorporation of sodium deoxycholate is essential for achieving precise control over drug release kinetics, overcoming previous limitations of silk-based systems as drug vehicles for multiple drugs. The model could provide an avenue to incorporate multiple drugs in a single delivery vehicle which would be very relevant during combinatorial therapies for preventing drug resistance, targeting multiple treatment pathways, increasing treatment success, or reducing side effects.

Keywords

drug delivery, silk biomaterials, controlled release, ciprofloxacin, dexamethasone, biomedical engineering

Document Type

Journal Article

Date of Publication

1-1-2026

E-ISSN

26335409

Publication Title

Materials Advances

Publisher

Royal Society of Chemistry

School

Mineral Recovery Research Centre / School of Engineering

Funding Information

The authors would also like to acknowledge the philanthropic support of Channel 7 Telethon and The Ian Potter Foundation for funding the Jeol 7000 SEM and sputter coater.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Recommended Citation

Bacal, C. J. O., Dorishetty, P., Allardyce, B. J., Piyumantha, N., Ejeian, F., Razmjou, A., Clark, S., Thornton, R., & Valente, F. (2026). Controlled and long-term multi-drug release from silk films. Materials Advances, 7(19), 9857–9871. https://doi.org/10.1039/d6ma00627b

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Link to publisher version (DOI)

10.1039/d6ma00627b