Exploiting Fat Absorption to Enhance Oral Bioavailability of Drugs

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Researchers at the ARC Centre of Excellence in Convergent Bio-Nano Science (CBNS) in Melbourne, Australia have developed a drug-delivery technology that circumvents first pas metabolism in the liver, thereby, enabling higher drug levels to reach the systemic circulation.

Researchers at the ARC Centre of Excellence in Convergent Bio-Nano Science (CBNS) in Melbourne, Australia, have published a patented technology of drug delivery that exploits fat absorption pathways, thereby, enabling orally administered drugs to circumvent the liver and avoid first pass metabolism. The liver functions as a filter that protects the body from foreign materials. Because of this protective mechanism, most orally administered drugs tend to be broken down in the liver, hence, reducing the amount of drug entering the bloodstream and reaching the site of action.

In this approach, a natural nano-scale lipid transport system is used to deliver the drug from the small intestine, through the lymphatic system, directly into the blood circulation. According to findings published in the European journal Angewandte Chemie International Edition, the technology has been evaluated in animal studies, using testosterone as the model drug. Professor Chris Porter, from CBNS, however, noted that the technology can potentially be applied to a range of drugs that suffer from first pass metabolism in the liver as well as molecules targeted to the lymphatic system.

Professor Porter and his team from the CBNS at the Monash Institute of Pharmaceutical Sciences, have been working on their technology, which specifically targets drug absorption via the lymphatic system and avoids the liver (i.e., the hepatic portal blood). The technology chemically modifies the drug so that it resembles dietary fats and is absorbed through the lipid digestion system.

According to Professor Porter, this drug-delivery technology has two main 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," he said in a press statement.

"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, for example, fight cancer, or to suppress the immune system to fight autoimmune diseases such as Crohn's Disease."


Using testosterone as the model drug, researchers have found that their new delivery system enhances drug uptake into the intestinal lymphatics. Testosterone levels in the blood were up to 90 times higher were observed compared to the current commercial product.

"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," Professor Porter said.

Source: Science Daily