New system allows direct absorption of a drug and prevents first past metabolism.
By piggybacking onto natural fat absorption pathways, the utility of some drugs could be increased since they can now be absorbed directly via bypassing the liver.
Some medications never make it into the bloodstream because they are broken down in the liver first. Researchers have tried to prevent this process, called first past metabolism, since it prevents the drug from being useful.
However, Australian researchers created a patented technology that allows oral drugs to bypass the liver, according to a study published by Angewandte Chemie International Edition.
The researchers tested the delivery of testosterone through the new technique in animal models, but say that it could be used for other drugs that are susceptible to first past metabolism, such as lymphatic system drugs. Although the liver is able to filter toxins efficiently, it can also limit the efficacy of drugs.
"No matter how good the drug is, it needs to be absorbed (into the bloodstream) and to avoid this first pass metabolism in order to get to the general circulation where it acts," said researcher Christopher J.H. Porter, PhD.
In the study, researchers fine-tuned pro-drug technology that targets absorption to the lymphatic system, rather than through the liver. The technology is able to modify the drug, so it chemically mimics dietary lipids, since lipids are assembled into nano-sized lipid droplets and transported to the blood via the lymph after absorption, according to the study.
Researchers believe that the pro-drug technology has major benefits.
“Firstly, the lymphatics drain directly into the blood and do not pass through the liver. This can dramatically enhance the efficiency of drugs with first pass metabolism problems like testosterone,” Dr Porter said. “Second, the lymphatic system is a key part of the immune system and helps fight disease and regulates the immune response to infection. Drug delivery directly into the lymph may therefore enhance the utility of drugs that are designed to stimulate the immune system to eg. fight cancer, or to suppress the immune system to fight autoimmune diseases such as Crohn's Disease.”
Researchers found that their technology was able to boost the uptake of the drug to the intestinal lymphatics. They discovered that with their new technology, blood levels of testosterone were 90 times higher compared with standard treatment, according to the study.
“The advantage of our system is that drugs are shielded from degradation in the liver but are ultimately released when they reach their site of action, ensuring that the drug given to the patient goes where it is supposed to,” Dr Porter concluded.