Influence of material format and surface chemistry for the sustained delivery and efficacy of silk drug delivery systems in vivo

Abstract

Silk fibroin materials are promising for use in controlled drug delivery in the field of tissue engineering and biomedical applications thanks to silk's generally established biocompatibility and tunable properties for implants and drug storage. Several factors must be considered in the materials design, including material format, drug properties and release kinetics, and the activity and stability of the drug after release. While numerous reviews described silk-based DDS that demonstrated controllable in vitro release, success in vivo has been limited, especially in some material formats. This review therefore aims to provide insight into the current material format and functionalization strategies to maximize in vivo performance by describing the in vivo activity of recently developed silk drug delivery systems. The review also aims to provide a fresh perspective on the suitable format and functionalization strategies for a target biomedical application. Based on the release behavior of drugs in various material formats, silk films, foams, and microneedles were better suited to serve as scaffolds for cell regeneration and improved recovery rate for biomedical applications involving wound healing and tissue engineering. Gels and particles could be incorporated within the films and foams but the purpose would be to serve as additional physical barriers towards drug diffusion in these types of application. For drugs or therapeutics that target internal organs (i.e. brain, liver, intestines, etc.), gels and particles were mainly used due to their size. In the event that the material format selection based on the target application does not contribute a lot to the prolonged release of drugs or therapeutic agents, hybrid functionalization strategies were adapted to make the surface chemistry of the material more responsive to the environmental stimuli for a more tunable silk DDS.