A Prodrug Nanoparticle Approach for the Oral Delivery of a Hydrophilic Peptide, Leucine(5)-enkephalin, to the Brain.

Submitted by info on Mon, 05/21/2012 - 11:38pm
TitleA Prodrug Nanoparticle Approach for the Oral Delivery of a Hydrophilic Peptide, Leucine(5)-enkephalin, to the Brain.
Publication TypeJournal Article
Year of Publication2012
AuthorsLalatsa A, Lee V, Malkinson JP, Zloh M, Schätzlein AG, Uchegbu IF
JournalMol Pharm
Volume9
Issue6
Pagination1665-80
Date Published2012 Jun 4
ISSN1543-8392
AbstractThe oral use of neuropeptides to treat brain disease is currently not possible because of a combination of poor oral absorption, short plasma half-lives and the blood-brain barrier. Here we demonstrate a strategy for neuropeptide brain delivery via the (a) oral and (b) intravenous routes. The strategy is exemplified by a palmitic ester prodrug of the model drug leucine(5)-enkephalin, encapsulated within chitosan amphiphile nanoparticles. Via the oral route the nanoparticle-prodrug formulation increased the brain drug levels by 67% and significantly increased leucine(5)-enkephalin's antinociceptive activity. The nanoparticles facilitate oral absorption and the prodrug prevents plasma degradation, enabling brain delivery. Via the intravenous route, the nanoparticle-prodrug increases the peptide brain levels by 50% and confers antinociceptive activity on leucine(5)-enkephalin. The nanoparticle-prodrug enables brain delivery by stabilizing the peptide in the plasma although the chitosan amphiphile particles are not transported across the blood-brain barrier per se, and are excreted in the urine.
DOI10.1021/mp300009u
Alternate JournalMol. Pharm.
PubMed ID22574705