Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia
Godfrey, Lisa and Iannitelli, Antonio and Garrett, Natalie L. and Moger, Julian and Imbert, Ian and King, Tamara and Porreca, Frank and Soundararajan, Ramesh and Lalatsa, Aikaterini and Schätzlein, Andreas G. and Uchegbu, Ijeoma F. (2018) Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia. Journal of Controlled Release, 270. pp. 135-144. ISSN 0168-3659 (https://doi.org/10.1016/j.jconrel.2017.11.041)
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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.
ORCID iDs
Godfrey, Lisa, Iannitelli, Antonio, Garrett, Natalie L., Moger, Julian, Imbert, Ian, King, Tamara, Porreca, Frank, Soundararajan, Ramesh, Lalatsa, Aikaterini ORCID: https://orcid.org/0000-0003-4791-7468, Schätzlein, Andreas G. and Uchegbu, Ijeoma F.;-
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Item type: Article ID code: 80838 Dates: DateEvent28 January 2018Published22 December 2017Published Online25 November 2017AcceptedSubjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 19 May 2022 15:11 Last modified: 19 Dec 2024 17:21 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/80838