Silk Fibroin-Based Coatings for Pancreatin-Dependent Drug Delivery

J Pharm Sci. 2024 Mar;113(3):718-724. doi: 10.1016/j.xphs.2023.09.001. Epub 2023 Sep 9.

Abstract

Triggerable coatings, such as pH-responsive polymethacrylate copolymers, can be used to protect the active pharmaceutical ingredients contained within oral solid dosage forms from the acidic gastric environment and to facilitate drug delivery directly to the intestine. However, gastrointestinal pH can be highly variable, which can reduce delivery efficiency when using pH-responsive drug delivery technologies. We hypothesized that biomaterials susceptible to proteolysis could be used in combination with other triggerable polymers to develop novel enteric coatings. Bioinformatic analysis suggested that silk fibroin is selectively degradable by enzymes in the small intestine, including chymotrypsin, but resilient to gastric pepsin. Based on the analysis, we developed a silk fibroin-polymethacrylate copolymer coating for oral dosage forms. In vitro and in vivo studies demonstrated that capsules coated with this novel silk fibroin formulation enable pancreatin-dependent drug release. We believe that this novel formulation and extensions thereof have the potential to produce more effective and personalized oral drug delivery systems for vulnerable populations including patients that have impaired and highly variable intestinal physiology.

Keywords: Enteric coating; In vivo validation; Pancreatin-dependent drug delivery; Silk fibroin–polymethacrylate copolymers; Triggered release.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Delivery Systems
  • Fibroins*
  • Humans
  • Pancreatin
  • Polymers
  • Polymethacrylic Acids
  • Silk

Substances

  • Fibroins
  • polymethacrylic acid
  • Pancreatin
  • Polymethacrylic Acids
  • Polymers
  • Silk