Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia
Garrett, Natalie L.
Schätzlein, Andreas G.
Uchegbu, Ijeoma F.
AffiliationUniv Arizona, Coll Med, Dept Pharmacol
Delta opioid receptor
MetadataShow full item record
PublisherELSEVIER SCIENCE BV
CitationGodfrey, L., Iannitelli, A., Garrett, N. L., Moger, J., Imbert, I., King, T., Porreca, F. & Uchegbu, I. F. (2018). Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia. Journal of Controlled Release, 270, 135-144.
JournalJOURNAL OF CONTROLLED RELEASE
Rights© 2017 The Authors. Published by Elsevier B.V.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractThe 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 leucine(5)-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.
NoteOpen access article
VersionFinal published version
SponsorsUK Engineering and Physical Sciences Research Council [EP/K502340/1]; Nanomerics Ltd. [NM12TSB-NPP]; Innovate UK [16939-124181]