Intestinal permeation enhancers: Lessons learned from studies using an organ culture model

Area of Science:

• Pharmacology and Drug Delivery
• Gastrointestinal Physiology

Background:

• Permeation enhancers (PEs) are crucial for improving the intestinal absorption of orally administered drugs with low bioavailability.
• Understanding the mechanisms by which PEs interact with the intestinal epithelium is essential for effective drug formulation.

Purpose of the Study:

• To review recent findings on permeation enhancers using an intestinal organ culture model.
• To elucidate the effects of different classes of PEs, specifically surfactants and cell penetrating peptides, on intestinal transport pathways.

Main Methods:

• Utilized an intestinal organ culture model to predict drug permeation pathways.
• Investigated the effects of surfactants and cell penetrating peptides on paracellular and transcellular transport.
• Analyzed the impact of PEs on transmembrane pathway generation, endocytosis, and cell membrane integrity.

Main Results:

• Permeation enhancers can create transmembrane transcellular pathways.
• Certain PEs, including surfactants and cell penetrating peptides, can inhibit apical endocytosis, a key step in transcytosis.
• These PEs also disrupt normal cell membrane integrity.

Conclusions:

• Surfactants and cell penetrating peptides are not ideal for oral drug delivery formulations designed to utilize transcytosis.
• The mechanisms of action of PEs suggest limitations for specific drug delivery strategies involving epithelial transport.