Ultrasound-mediated gastrointestinal drug delivery
Author(s)Brugge, W. R.; Lauwers, Gregory Yves; Schoellhammer, Carl Magnus; Swiston Jr, Albert J.; Zervas, Michael J.; Traverso, Carlo Giovanni; Anderson, Daniel Griffith; Blankschtein, Edmundo D; Langer, Robert S; Maa, Ruby C.; Schroeder, Avraham Dror; Barman, Ross; DiCiccio, Angela M; ... Show more Show less
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There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn’s and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.
available in PMC 2016 April 08
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Mechanical Engineering
Science Translational Medicine
American Association for the Advancement of Science (AAAS)
Schoellhammer, C. M., A. Schroeder, R. Maa, G. Y. Lauwers, A. Swiston, M. Zervas, R. Barman, et al. “Ultrasound-Mediated Gastrointestinal Drug Delivery.” Science Translational Medicine 7, no. 310 (October 21, 2015): 310ra168–310ra168.
Author's final manuscript