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Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site

Muresan, Paula; McCrorie, Phoebe; Smith, Fiona; Vasey, Catherine; Taresco, Vincenzo; Scurr, David J; Kern, Stefanie; Smith, Stuart; Gershkovich, Pavel; Rahman, Ruman; Marlow, Maria

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Authors

Paula Muresan

Fiona Smith

Catherine Vasey

DAVID SCURR DAVID.SCURR@NOTTINGHAM.AC.UK
Principal Research Fellow

Stefanie Kern

STUART SMITH stuart.smith@nottingham.ac.uk
Clinical Associate Professor



Abstract

Systemic drug delivery to the central nervous system (CNS) has been historically impeded by the presence of the blood brain barrier rendering many therapies inefficacious to any cancer cells residing within the brain. Therefore, local drug delivery systems are being developed to overcome this shortfall. Here we have manufactured polymeric microneedle (MN) patches, which can be anchored within a resection cavity site following surgical removal of a tumour such as isocitrate dehydrogenase wild type glioblastoma (GBM). These biodegradable MN patches have been loaded with polymer coated nanoparticles (NPs) containing cannabidiol (CBD) or olaparib (OLA) and applied to an in vitro brain simulant and ex vivo rat brain tissue to assess drug release and distance of penetration. MN patches loaded with methylene blue dye were placed into a cavity of 0.6% agarose to simulate brain tissue. The results showed that clear channels were generated by the MNs and the dye spread laterally throughout the agarose. When loaded with CBD-NPs, the agarose showed a CBD concentration of 12.5 µg/g at 0.5 cm from the MN insertion site. Furthermore, high performance liquid chromatography of ex vivo brain tissue following CBD-NP/MN patch insertion showed successful delivery of 59.6 µg/g into the brain tissue. Similarly, OLA-NP loaded MN patches showed delivery of 5.2 µg/g OLA into agarose gel at 0.5 cm distance from the insertion site. Orbitrap secondary ion mass spectrometry (OrbiSIMS) analysis confirmed the presence of OLA and the MN patch at up to 6 mm away from the insertion site following its application to a rat brain hemisphere. This data has provided insight into the capabilities and versatility of MN patches for use in local brain drug delivery, giving promise for future research.

Citation

Muresan, P., McCrorie, P., Smith, F., Vasey, C., Taresco, V., Scurr, D. J., …Marlow, M. (2023). Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site. European Journal of Pharmaceutics and Biopharmaceutics, 182, 53-61. https://doi.org/10.1016/j.ejpb.2022.11.016

Journal Article Type Article
Acceptance Date Nov 16, 2022
Online Publication Date Nov 24, 2022
Publication Date 2023-01
Deposit Date Dec 1, 2022
Publicly Available Date Nov 25, 2023
Journal European Journal of Pharmaceutics and Biopharmaceutics
Print ISSN 0939-6411
Electronic ISSN 1873-3441
Publisher Elsevier BV
Peer Reviewed Peer Reviewed
Volume 182
Pages 53-61
DOI https://doi.org/10.1016/j.ejpb.2022.11.016
Keywords Microneedles, nanoparticles, isocitrate dehydrogenase wild type glioblastoma
Public URL https://nottingham-repository.worktribe.com/output/14315663
Publisher URL https://www.sciencedirect.com/science/article/abs/pii/S0939641122002752?via%3Dihub

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