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Nanoparticulate Peptide Delivery Exclusively to the Brain Produces Tolerance Free Analgesia

Godfrey, L; Iannitelli, A; Garrett, NL; Moger, J; Imbert, I; King, T; Porreca, F; ... Uchegbu, IF; + view all (2018) Nanoparticulate Peptide Delivery Exclusively to the Brain Produces Tolerance Free Analgesia. Journal of Controlled Release , 270 pp. 135-144. 10.1016/j.jconrel.2017.11.041. Green open access

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Abstract

The delivery of peptide drugs to the brain is challenging, principally due to the blood brain barrier and the low metabolic stability of peptides. Exclusive delivery to the brain with no peripheral exposure has hitherto not been demonstrated with brain quantification data. Here we show that polymer nanoparticles encapsulating leucine5-enkephalin hydrochloride (LENK) are able to transport LENK exclusively to the brain via the intranasal route, with no peripheral exposure and nanoparticle localisation is observed within the brain parenchyma. Animals dosed with LENK nanoparticles (NM0127) showed a strong anti-nociceptive response in multiple assays of evoked and on going pain whereas animals dosed intranasally with LENK alone were unresponsive. Animals did not develop tolerance to the anti-hyperalgesic activity of NM0127 and NM0127 was active in morphine tolerant animals. A microparticulate formulation of clustered nanoparticles was prepared to satisfy regulatory requirements for nasal dosage forms and the polymer nanoparticles alone were found to be biocompatible, via the nasal route, on chronic dosing.

Type: Article
Title: Nanoparticulate Peptide Delivery Exclusively to the Brain Produces Tolerance Free Analgesia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jconrel.2017.11.041
Publisher version: http://doi.org/10.1016/j.jconrel.2017.11.041
Language: English
Additional information: © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Keywords: Nanoparticles; Microparticles; Chitosan amphiphiles; Leucine5-enkephalin; Intranasal; Analgesia; Brain delivery; Delta opioid receptor
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10039394
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