Oral Delivery of Macromolecules

Certain drugs that are large proteins cannot be administered orally due to their slow transportation across the intestinal membrane. Chemical enhancers can increase the permeability of this membrane. Single enhancers have limited use as their potency is often linked to their toxicity. Therefore, we searched for synergistic combinations of these permeation enhancers that work better than their single counterparts. We performed a series of enhancement potential experiments on Caco-2 cell monolayers that mimic the epithelial membrane in the intestine, and recorded the resistance of the monolayer after being exposed to the enhancer combinations for fixed time intervals. We tested 16 different enhancers from nine chemically distinct categories. Based on current results, we concluded that zwittorionic surfactants and fatty esters are more likely to produce synergistic combinations than any other categories. This study has provided the preliminary results needed to intelligently select the enhancers we choose to study in the future.