Two bioengineers explain how we could deliver drugs that better withstand stomach acid

To compensate for degradation in the stomach, oral medications typically come in doses that are higher than necessary. This strategy works for many common small-molecule drugs that have a low mass. They are often more stable and can more easily enter cells compared to other types of drugs. However, increasing dosage is not a viable approach for treatments that easily build up to toxic levels, are too sensitive to the acidity of the stomach, or are very costly.

A stomach acid-resistant material

To help drugs withstand the harsh environment of the stomach, our research team developed a new type of material called polyzwitterionic complexes, or pZCs. pZCs are composed of two types of polymers, or large molecules made of a string of repeating smaller molecules. As the name suggests, pZCs are made of polyzwitterions, which are both positively and negatively charged, and polyelectrolytes, which are exclusively positive or negative.

Through a process called complex coavcervation that joins oppositely charged molecules, these two polymers self-assemble to form pZC droplets that are sensitive to acidity. In principle, these droplets could encapsulate and protect a therapeutic cargo as it travels through the highly acidic stomach, but disassemble and release the drug upon reaching the more neutral environment of the small intestine.

We first tested whether the pZC droplets were able to encapsulate a protein as a test cargo. Once we were successfully able to place the cargo in the droplet, we then measured how much protein cargo was released in varying levels of acidity through spectrophotometry, a method that uses light absorption to measure the amount of substance present in a sample. We found that the pZC droplets retained their protein cargo in acidic conditions and steadily released it as acidity decreased.