Computationally guided high-throughput design of self-assembling drug nanoparticles.

Journal Article (Journal Article)

Nanoformulations of therapeutic drugs are transforming our ability to effectively deliver and treat a myriad of conditions. Often, however, they are complex to produce and exhibit low drug loading, except for nanoparticles formed via co-assembly of drugs and small molecular dyes, which display drug-loading capacities of up to 95%. There is currently no understanding of which of the millions of small-molecule combinations can result in the formation of these nanoparticles. Here we report the integration of machine learning with high-throughput experimentation to enable the rapid and large-scale identification of such nanoformulations. We identified 100 self-assembling drug nanoparticles from 2.1 million pairings, each including one of 788 candidate drugs and one of 2,686 approved excipients. We further characterized two nanoparticles, sorafenib-glycyrrhizin and terbinafine-taurocholic acid both ex vivo and in vivo. We anticipate that our platform can accelerate the development of safer and more efficacious nanoformulations with high drug-loading capacities for a wide range of therapeutics.

Full Text

Duke Authors

Cited Authors

  • Reker, D; Rybakova, Y; Kirtane, AR; Cao, R; Yang, JW; Navamajiti, N; Gardner, A; Zhang, RM; Esfandiary, T; L'Heureux, J; von Erlach, T; Smekalova, EM; Leboeuf, D; Hess, K; Lopes, A; Rogner, J; Collins, J; Tamang, SM; Ishida, K; Chamberlain, P; Yun, D; Lytton-Jean, A; Soule, CK; Cheah, JH; Hayward, AM; Langer, R; Traverso, G

Published Date

  • June 2021

Published In

Volume / Issue

  • 16 / 6

Start / End Page

  • 725 - 733

PubMed ID

  • 33767382

Pubmed Central ID

  • PMC8197729

Electronic International Standard Serial Number (EISSN)

  • 1748-3395

International Standard Serial Number (ISSN)

  • 1748-3387

Digital Object Identifier (DOI)

  • 10.1038/s41565-021-00870-y


  • eng