Optimising the production of PLGA nanoparticles by combining design of experiment and machine learning

Seegobin, Nidhi; Abdalla, Youssef; Li, Ge; Murdan, Sudaxshina; Shorthouse, David; Basit, Abdul W.

doi:10.1016/j.ijpharm.2024.124905

International Journal of Pharmaceutics

2024

DOI: 10.1016/j.ijpharm.2024.124905

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Optimising the production of PLGA nanoparticles by combining design of experiment and machine learning

Nidhi Seegobin,

Youssef Abdalla,

Ge Li

et al.

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Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model

Seegobin,

McCoubrey,

Vignal

et al. 2024

Drug Deliv. and Transl. Res.

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Inflammatory bowel disease (IBD) affects over 7 million people worldwide and significant side effects are associated with current therapies such as tofacitinib citrate (TFC), which is linked to increased risks of malignancy and congestive heart issues. To mitigate these systemic adverse effects, localised drug delivery via nano-sized carriers to inflamed gut tissues represents a promising approach. Herein, we aimed to optimise the synthesis of nanoparticles (NPs) using a low molecular weight grade of Poly(lactic-co-glycolic acid) (PLGA) 50:50 loaded with TFC. This approach leverages the dual anti-inflammatory action of TFC and the local production of anti-inflammatory short-chain fatty acids from the degradation of PLGA by colonic gut microbiota. NPs were produced by nanoprecipitation and characterised for their drug release profile in vitro. The efficacy of the enhanced PLGA-TFC NPs was then tested in a C57BL/6 DSS colitis mouse model. The release profile of TFC from the enhanced PLGA NPs showed a 40% burst release within the first hour, followed by up to 80% drug release in the colonic environment. Notably, the degradation of PLGA by colonic gut microbiota did not significantly influence TFC release. In the mouse model, neither PLGA NPs alone nor TFC alone showed significant effects on weight loss compared to the TFC-loaded PLGA NPs, emphasising the enhanced efficacy potential of the combined formulation. Altogether, these results suggest a promising role of NP delivery systems in enhancing TFC efficacy, marking a significant step towards reducing dosage and associated side effects in IBD treatment. This study underscores the potential of PLGA-TFC NPs in providing targeted and effective therapy for IBD. Graphical Abstract

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Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model

Seegobin,

McCoubrey,

Vignal

et al. 2024

Drug Deliv. and Transl. Res.

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show abstract

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Optimising the production of PLGA nanoparticles by combining design of experiment and machine learning

Cited by 1 publication

References 40 publications

Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model

Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model

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