Engineering controlled-release steroid therapeutics: fabrication and molecular design of self-assembled microparticles

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Abstract
Steroids, specifically bile salts and corticosteroids, treat bile synthesis disorders, liver dysfunction, and inflammation. However, these water-soluble steroid drugs are rapidly cleared from the desired sites of action in the body, necessitating multiple doses. Therefore, the development of particle-based steroid medications that offer elongated therapeutic activity is of paramount medical importance. Accordingly, steroid microparticles were developed via three fabrication processes in this work, where a metal or an organic acid facilitates steroid microparticle formation. Particles fabricated using these methods exhibit consistent shape, size, and crystallinity. Furthermore, results from our coarse-grained computational model show that hydrogen bonding dictates steroid monomer-monomer interactions that determine overall particle shape and size. In addition, we demonstrate the ability to induce steroid particle formation and tune the morphology of steroid drug particles by replacing the C21 side group (tail) with chemical analogs. Thus, this study opens opportunities for the clinical translation of particle-based steroid therapeutics as an alternative to the current steroid drug formulations.
Funding Information
  • National Science Foundation (DMR-1941731)
  • National Institutes of Health (NIH R21 AR080502-01A1)
  • National Institutes of Health (T32GM145304)
  • Johns Hopkins University (Start-up funds)
  • Johns Hopkins University (Advanced Research Computing Facility (ARCH))
  • Fast Forward Medical Innovation Mi-Kickstart and mid-stage MTRAC grants
  • AFOSR YIP Award (# FA9550-24-1-0100)

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