A prodrug nanoparticle approach for the oral delivery of a hydrophilic peptide, leucine(5)-enkephalin, to the brain.
|Title||A prodrug nanoparticle approach for the oral delivery of a hydrophilic peptide, leucine(5)-enkephalin, to the brain.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Lalatsa A, Lee V, Malkinson JP, Zloh M, Schätzlein AG, Uchegbu IF|
|Date Published||2012 Jun 4|
|Keywords||Administration, Oral, Animals, Blood-Brain Barrier, Brain, Enkephalins, Hydrophobic and Hydrophilic Interactions, Magnetic Resonance Spectroscopy, Male, Mass Spectrometry, Mice, Nanoparticles, Peptides, Prodrugs, Rats, Rats, Wistar|
The 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.
|Alternate Journal||Mol. Pharm.|
|Grant List||/ / Wellcome Trust / United Kingdom|