Small-molecule therapeutics treat a wide variety of diseases, but their effectiveness is often diminished because of their pharmacokinetics — what the body does to a drug. After administration, the body dictates how much of the drug is absorbed, which organs the drug enters, and how quickly the body metabolizes and excretes the drug again.
Nanoparticles, usually made out of lipids, polymers, or both, can improve the pharmacokinetics, but they can be complex to produce and often carry very little of the drug.
Some combinations of small-molecule cancer drugs and two small-molecule dyes have been shown to self-assemble into nanoparticles with extremely high payloads of drugs, but it is difficult to predict which small-molecule partners will form nanoparticles among the millions of possible pairings.
MIT researchers have developed a screening platform that combines machine learning with high-throughput experimentation to identify self-assembling nanoparticles quickly. In a study published in Nature Nanotechnology, researchers screened 2.1 million pairings of small-molecule drugs and “inactive” drug ingredients, identifying 100 new nanoparticles with potential applications that include the treatment of cancer, asthma, malaria, and viral and fungal infections.
“We have previously described some of the negative and positive effects that inactive ingredients can have on drugs, and here, through a concerted collaboration across our laboratories and core facilities, describe an approach focusing on the potential positive effects these can have on nanoformulation,” says Giovanni Traverso, the Karl Van Tassel (1925) Career Development Professor of Mechanical Engineering, and senior corresponding author of the study.
Their findings point to a strategy for that solves for both the complexity of producing nanoparticles and the difficulty of loading large amounts of drugs onto them.
“So many drugs out there don’t live up to their full potential because of insufficient targeting, low bioavailability, or rapid drug metabolism,” says Daniel Reker, lead author of the study and a former postdoc in the laboratory of Robert Langer. “By working at the interface of data science, machine learning, and drug delivery, our hope is to rapidly expand our tool set for making sure a drug gets to the place it needs to be and can actually treat and help a human being.”
Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute for Integrative Cancer Research, is also a senior author of the paper.
A cancer therapy meets its match
In order to develop a machine learning algorithm capable of identifying self-assembling nanoparticles, researchers first needed to build a dataset on which the algorithm could train. They selected 16 self-aggregating smal
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