Low-frequency ultrasound for the delivery of therapeutics to the gastrointestinal tract

Abstract

Rapid and effective drug delivery to the gastrointestinal (GI) tract can be a significant challenge. This is because of the harsh environment present in the GI tract and fast transit times in disease states. Physical enhancers, such as ultrasound (US), may enable the rapid delivery of therapeutics while circumventing the need for formulation development. Despite being investigated for other uses, low frequency US has not been studied for GI-based delivery previously. Our group has developed a hand-held device for the rapid delivery of therapeutics to the colonic mucosa. The device utilizes low-frequency US, which is able to painlessly and reversibly permeabilize the tissue. Short, 1-minute treatments in 80 kg Yorkshire pigs were found to enhance the delivery of mesalamine, a drug used for the treatment of inflammatory bowel disease, 22.4-fold over a conventional enema. The safety and efficacy of US were further validated in a rodent colitis model. The delivery of proteins was also possible. US-mediated GI delivery has many potential applications ranging from localized treatment with anti-inflammatories to the more broad delivery of macromolecules. This new technology could prove invaluable in both clinical and research settings, enabling improved therapies and expansion of research techniques applied to the GI tract.

Getting Drugs Across Biological Barriers

“…For example, a more than 20-fold enhancement of drug permeation compared to a conventional enema has been achieved by applying a 1-minute treatment of low-frequency ultrasound generated by a rectal probe in Yorkshire pigs. [259] Similar enhancement can be achieved for the delivery of hydrocortisone and mesalamine. [136] …”

Recent advances in mesalamine colonic delivery systems

“…This approach employs a low frequency ultrasound to trigger drug delivery at lower GIT via causing transient cavitation, which produce microjets to enhance drug permeation through gastrointestinal mucosa [46]. Schoellhammer et al [47] reported the development a hand-held device, which use a low frequency ultrasound, as a reversible and painless method to enhance mesalamine delivery in the treatment of ulcerative colitis and Crohn' disease. This device was coadministered superficially into the rectum of Yorkshire pigs with a mesalamine enema.…”