New paper in Nature Nanotechnology

Our computational nanoparticle design work was just published in Nature Nanotechnology.

Nanoparticles are an important drug delivery tool to improve targeting, stability, or safety of medications. However, they are often complex to manufacture and carry only very little drug. Recent work in the laboratories of Brian & Molly Shoichet and Dan Heller has shown that self-assembly of chemotherapeutics with molecular dyes leads to ultra-highly loaded nanoparticles. We wondered whether this phenomena is applicable to a broader range of drugs and using other excipients.

We developed a platform consisting of high-throughput experiments, molecular simulations, and machine learning to assess the co-aggregation potential of 2.1 million possible combinations of drugs with excipients such as established food and drug additives. We identified 100 novel nanoparticles, and showed that they can improve drug dispersion. We further characterized two nanoparticles as proof of concepts. Terbinafine – taurocholic acid as a potential antifungal therapy and sorafenib – glycyrrhizins for applications in cancer therapy. The nanoparticles improve targeting to the desired tissue in vitro, ex vivo, and in vivo. For the sorafenib – glycyrrhizin particles, we performed a full in vivo validation and show that the particles are better at treating liver cancer compared to any of the control treatments.

Given ease of synthesis and high drug loading, we expect that this platform will facilitate the generation of novel nanomedicines. Through “mix and match” of drugs and excipients, we hope this will provide a new path for personalized drug delivery.