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Optimisation and feature selection of poly-beta-amino-ester as a drug delivery system for cartilage

Perni, Stefano and Prokopovich, Polina 2020. Optimisation and feature selection of poly-beta-amino-ester as a drug delivery system for cartilage. Journal of Materials Chemistry. B 8 (23) , pp. 5096-5108. 10.1039/C9TB02778E

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Abstract

Drug localisation is still one of the main challenges in treating pathologies affecting cartilage; poly-beta-amino-esters (PBAEs) drug conjugates are a possible solution; however, their efficacy highly depends on the polymer structure hence the full potential of this delivery system is still unknown. For the purpose of optimising the delivery system design, a large library of PBAEs was synthesised and dexamethasone (DEX) uptake in cartilage was determined. All three components of PBAE (amine, acrylate and end-capping) impacted the outcome. The most effective PBAE identified enhanced DEX uptake by 8 folds compared to an equivalent dose of the commercial formulation and also prevented, through delivery of DEX, the cartilage degradation caused by IL-1α (interleukine1α). A chemometrics based predictive model was constructed and PBAEs properties most affecting the performance of the drug delivery systems were identified. This model will allow further computer based PBAEs optimisation and fast track the bench to market process for this delivery system.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Royal Society of Chemistry
ISSN: 2050-750X
Funders: Wellcome Trust
Date of First Compliant Deposit: 18 May 2020
Date of Acceptance: 14 April 2020
Last Modified: 02 Jul 2020 10:41
URI: http://orca-mwe.cf.ac.uk/id/eprint/131767

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