To compensate for the breakdown in the stomach, oral medications usually come in doses that: higher than necessary† This strategy works for many common small molecule drugs that have a low mass. They are often more stable and can penetrate cells more easily compared to other types of drugs. However, increasing the dose is not a viable approach for treatments that easily reach toxic levels, are too sensitive to stomach acidity, or are very expensive.
A stomach acid resistant material
To help drugs withstand the harsh environment of the stomach, our research team has developed a new type of material called polyzwitterionic complexes, or pZCs† pZCs are composed of two types polymers, or large molecules made of a series of repeating smaller molecules. As the name suggests, pZCs are made of: polyzwitterionsthat are both positively and negatively charged, and polyelectrolytesthat are exclusively positive or negative.
Through a process called complex coavcervation connecting 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 break apart and release the drug upon reaching the more neutral environment of the small intestine.
We first tested whether the pZC droplets could encapsulate a protein as a test payload. After successfully placing the charge in the droplet, we measured how much protein charge was released in different acidities by spectrophotometry, a method that uses light absorption to measure the amount of substance in a sample. We found that the pZC droplets retained their protein charge in acidic conditions and released it steadily as the acidity decreased.
Making medicines more convenient
We believe that our pZC system could enable researchers to develop new and improved ways to deliver drugs through the gastrointestinal tract. Our future work will focus on a better understanding of how pZCs behave as their chemical properties change under different conditions. We are also experimenting with different types of polymers and drug loads.
We hope that our methods and conceptual framework will one day increase the number and variety of drugs that can be taken orally, making it easier to take your drug and improving patients’ lives.
Khatcher O. Margossian is an MD/PhD candidate in polymer science and engineering at the University of Massachusetts Amherst. Murugappan Muthukumar is a professor of polymer science and engineering at the University of Massachusetts Amherst.
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