What's Next for Gastrointestinal Disorders: No Needles?

J Control Release. 2016 Jan 10:221:48-61. doi: 10.1016/j.jconrel.2015.11.031. Epub 2015 Dec 2.

Abstract

A myriad of pathologies affect the gastrointestinal tract, citing this affected area as a significant target for therapeutic intervention. One group of therapeutic agents, antisense and oligonucleotides and small interfering RNAs, offer a promising platform for treating a wide variety of diseases ranging from cancer to auto-immune diseases. Current delivery methods are carried out either systemically or locally into diseased areas, both of which involve needles. The challenge in orally administering this type of treatment lies in the complications that arise due to the vast environmental extremes found within the gastrointestinal tract, owing to the fact that, as the drug travels down the gastrointestinal tract, it is subjected to pH changes and interactions with bacteria and a variety of digestive and protective enzymes including proteases, DNAses, and RNAses. Overcoming these challenges to allow the practical application of these drugs is a priority that has invoked a multitude of research in the chemical, biological, and material sciences. In this review, we will address common gastrointestinal pathologies, the barriers to oral-based therapies and antisense-interfering technologies, the approaches that have already been applied for their delivery, and the current status of antisense drug therapy clinical trials for gastrointestinal-related disorders.

Keywords: Antisense; Gastrointestinal tract; Oligonucleotides; Oral delivery; Small interfering RNAs.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems*
  • Gastrointestinal Diseases / pathology
  • Gastrointestinal Diseases / therapy*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology
  • Gene Transfer Techniques*
  • Humans
  • Needles
  • Oligonucleotides, Antisense / administration & dosage*
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / therapeutic use
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / therapeutic use

Substances

  • Oligonucleotides, Antisense
  • RNA, Small Interfering