Purpose: The purpose of this study was to evaluate formulation factors causing improvement in brain delivery of a small peptide after encapsulation into a targeted nanocarrier in vivo.
Methods: The evaluation was performed in rats using microdialysis, which enabled continuous sampling of the released drug in both the brain (striatum) and blood. Uptake in brain could thereby be studied in terms of therapeutically active, released drug.
Results: We found that encapsulation of the peptide DAMGO in fast-releasing polyethylene glycol (PEG)ylated liposomes, either with or without the specific brain targeting ligand glutathione (GSH), doubled the uptake of DAMGO into the rat brain. The increased brain delivery was observed only when the drug was encapsulated into the liposomes, thus excluding any effects of the liposomes themselves on the blood-brain barrier integrity as a possible mechanism. The addition of a GSH coating on the liposomes did not result in an additional increase in DAMGO concentrations in the brain, in contrast to earlier studies on GSH coating. This may be caused by differences in the characteristics of the encapsulated compounds and the composition of the liposome formulations.
Conclusions: We were able to show that encapsulation into PEGylated liposomes of a peptide with limited brain delivery could double the drug uptake into the brain without using a specific brain targeting ligand.
Keywords: blood–brain barrier; brain delivery; liposomes; microdialysis; opioid peptide.