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Feasibility and application of machine learning enabled fast screening of poly-beta-amino-esters for cartilage therapies

Perni, Stefano and Prokopovich, Polina ORCID: 2022. Feasibility and application of machine learning enabled fast screening of poly-beta-amino-esters for cartilage therapies. Scientific Reports 12 (1) , 14215. 10.1038/s41598-022-18332-3

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Despite the large prevalence of diseases affecting cartilage (e.g. knee osteoarthritis affecting 16% of population globally), no curative treatments are available because of the limited capacity of drugs to localise in such tissue caused by low vascularisation and electrostatic repulsion. While an effective delivery system is sought, the only option is using high drug doses that can lead to systemic side effects. We introduced poly-beta-amino-esters (PBAEs) to effectively deliver drugs into cartilage tissues. PBAEs are copolymer of amines and di-acrylates further end-capped with other amine; therefore encompassing a very large research space for the identification of optimal candidates. In order to accelerate the screening of all possible PBAEs, the results of a small pool of polymers (n = 90) were used to train a variety of machine learning (ML) methods using only polymers properties available in public libraries or estimated from the chemical structure. Bagged multivariate adaptive regression splines (MARS) returned the best predictive performance and was used on the remaining (n = 3915) possible PBAEs resulting in the recognition of pivotal features; a further round of screening was carried out on PBAEs (n = 150) with small variations of structure of the main candidates from the first round. The refinements of such characteristics enabled the identification of a leading candidate predicted to improve drug uptake > 20 folds over conventional clinical treatment; this uptake improvement was also experimentally confirmed. This work highlights the potential of ML to accelerate biomaterials development by efficiently extracting information from a limited experimental dataset thus allowing patients to benefit earlier from a new technology and at a lower price. Such roadmap could also be applied for other drug/materials development where optimisation would normally be approached through combinatorial chemistry.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Pharmacy
Additional Information: License information from Publisher: LICENSE 1: URL:, Type: open-access
Publisher: Nature Research
ISSN: 2045-2322
Funders: Wellcome Trust
Date of First Compliant Deposit: 22 August 2022
Date of Acceptance: 9 August 2022
Last Modified: 08 Sep 2023 17:07

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