Data-driven development of an oral lipid-based nanoparticle formulation of a hydrophobic drug.

Autor: Bao Z; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada., Yung F; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada., Hickman RJ; Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6, Canada.; Department of Computer Science, University of Toronto, Toronto, ON, M5S 2E4, Canada.; Vector Institute for Artificial Intelligence, Toronto, ON, M5S 1M1, Canada., Aspuru-Guzik A; Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6, Canada.; Department of Computer Science, University of Toronto, Toronto, ON, M5S 2E4, Canada.; Vector Institute for Artificial Intelligence, Toronto, ON, M5S 1M1, Canada.; Lebovic Fellow, Canadian Institute for Advanced Research (CIFAR), Toronto, ON, M5S 1M1, Canada.; Department of Chemical Engineering & Applied Chemistry, University of Toronto, Toronto, ON, M5S 3E5, Canada.; Department of Materials Science & Engineering, University of Toronto, Toronto, ON, M5S 3E4, Canada.; CIFAR Artificial Intelligence Research Chair, Vector Institute, Toronto, ON, M5S 1M1, Canada.; Acceleration Consortium, Toronto, ON, M5S 3H6, Canada., Bannigan P; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada. pauric.bannigan@utoronto.ca., Allen C; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada. cj.allen@utoronto.ca.; Department of Chemical Engineering & Applied Chemistry, University of Toronto, Toronto, ON, M5S 3E5, Canada. cj.allen@utoronto.ca.; Acceleration Consortium, Toronto, ON, M5S 3H6, Canada. cj.allen@utoronto.ca.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2024 Jul; Vol. 14 (7), pp. 1872-1887. Date of Electronic Publication: 2023 Dec 29.
DOI: 10.1007/s13346-023-01491-9
Abstrakt: Due to its cost-effectiveness, convenience, and high patient adherence, oral drug administration normally remains the preferred approach. Yet, the effective delivery of hydrophobic drugs via the oral route is often hindered by their limited water solubility and first-pass metabolism. To mitigate these challenges, advanced delivery systems such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been developed to encapsulate hydrophobic drugs and enhance their bioavailability. However, traditional design methodologies for these complex formulations often present intricate challenges because they are restricted to a relatively narrow design space. Here, we present a data-driven approach for the accelerated design of SLNs/NLCs encapsulating a model hydrophobic drug, cannabidiol, that combines experimental automation and machine learning. A small subset of formulations, comprising 10% of all formulations in the design space, was prepared in-house, leveraging miniaturized experimental automation to improve throughput and decrease the quantity of drug and materials required. Machine learning models were then trained on the data generated from these formulations and used to predict properties of all SLNs/NLCs within this design space (i.e., 1215 formulations). Notably, formulations predicted to be high-performers via this approach were confirmed to significantly enhance the solubility of the drug by up to 3000-fold and prevented degradation of drug. Moreover, the high-performance formulations significantly enhanced the oral bioavailability of the drug compared to both its free form and an over-the-counter version. Furthermore, this bioavailability matched that of a formulation equivalent in composition to the FDA-approved product, Epidiolex ® .
(© 2023. Controlled Release Society.)
Databáze: MEDLINE
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