Feasibility and Application of Machine Learning Enabled Fast Screening of Poly-Beta- Amino-Esters for Cartilage Therapies

Despite the large prevalence of diseases affecting cartilage (with knee osteoarthritis affecting 16% of population globally), no curative treatments are available because of the limited capacity of drugs to localise in such tissues caused by the 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) polymers 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 MARS returned the best performance and was used on the remaining (n = 3915) possible PBAEs resulting in the recognition of pivotal features; further refinements of such characteristics (n = 150) enabled the identification of a leading candidate predicted to improve drug uptake > 20 folds over conventional clinical treatment. 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.