Self-assembled polymersomes conjugated with lactoferrin as novel drug carrier for brain delivery

Abstract

Purpose: To develop a novel brain drug delivery system based on self-assembled poly(ethyleneglycol)-poly (D,L-lactic-co-glycolic acid) (PEG-PLGA) polymersomes conjugated with lactoferrin (Lf-POS). The brain delivery properties of Lf-POS were investigated and optimized.

Method: Three formulations of Lf-POS, with different densities of lactoferrin on the surface of polymersomes, were prepared and characterized. The brain delivery properties in mice were investigated using 6-coumarin as a fluorescent probe loaded in Lf-POS (6-coumarin-Lf-POS). A neuroprotective peptide, S14G-humanin, was incorporated into Lf-POS (SHN-Lf-POS); a protective effect on the hippocampuses of rats treated by Amyloid-β(25-35) was investigated by immunohistochemical analysis.

Results: The results of brain delivery in mice demonstrated that the optimized number of lactoferrin conjugated per polymersome was 101. This obtains the greatest blood-brain barrier (BBB) permeability surface area(PS) product and percentage of injected dose per gram brain (%ID/g brain). Immunohistochemistry revealed the SHN-Lf-POS had a protective effect on neurons of rats by attenuating the expression of Bax and caspase-3 positive cells. Meanwhile, the activity of choline acetyltransferase (ChAT) had been increased compared with negative controls.

Conclusion: These results suggest that lactoferrin functionalized self-assembled PEG-PLGA polymersomes could be a promising brain-targeting peptide drug delivery system via intravenous administration.