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Record W2976785851 · doi:10.1101/786251

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

2019· preprint· en· W2976785851 on OpenAlexaff
Daniel Reker, Yulia Rybakova, Ameya R. Kirtane, Ruonan Cao, Jee Won Yang, Natsuda Navamajiti, Apolonia Gardner, Rosanna M. Zhang, Tina Esfandiary, Johanna L’Heureux, Thomas von Erlach, Elena M. Smekalova, Dominique Leboeuf, Kaitlyn Hess, Aaron Lopes, Jaimie Rogner, Joy Collins, Siddartha Tamang, Keiko Ishida, P. Chamberlain, Dong Soo Yun, Abigail Lytoon-Jean, Christian K. Soule, Jaime H. Cheah, Alison Hayward, Róbert Langer, Giovanni Traverso

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacological Effects of Natural Compounds
Canadian institutionsUniversity of Toronto
FundersNational Cancer InstituteNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungSkolkovo Institute of Science and TechnologyKoch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyPharmaceutical Research and Manufacturers of America Foundation
KeywordsDrugNanotechnologyDrug discoveryNanoparticleComputer sciencePharmacologyChemistryMaterials scienceMedicine

Abstract

fetched live from OpenAlex

Abstract Nanoformulations are transforming our capacity to effectively deliver and treat a myriad of conditions. However, many nanoformulation approaches still suffer from high production complexity and low drug loading. One potential solution relies on harnessing co-assembly of drugs and small molecular excipients to facilitate nanoparticle formation through solvent exchange without the need for chemical synthesis, generating nanoparticles with up to 95% drug loading. However, there is currently no understanding which of the millions of possible combinations of small molecules can result in the formation of these nanoparticles. Here we report the development of a high-throughput screening platform coupled to machine learning to enable the rapid evaluation of such nanoformulations. Our platform identified 101 novel self-assembling drug nanoparticles from 2.1 million pairings derived from 788 candidate drugs with one of 2686 excipients, spanning treatments for multiple diseases and often harnessing well-known food additives, vitamins, or approved drugs as carrier materials – with potential for accelerated approval and translation. Given their long-term stability and potential for clinical impact, we further characterize novel sorafenib-glycyrrhizin and terbinafine-taurocholic acid nanoparticles ex vivo and in vivo . We anticipate that this platform could accelerate the development of safer and more efficacious nanoformulations with high drug loadings for a wide range of therapeutics.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.039
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.079
GPT teacher head0.360
Teacher spread0.282 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations11
Published2019
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicPharmacological Effects of Natural CompoundsFrench-language works237,207