Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson's disease following intranasal administration.

Odorranalectin (OL) was recently identified as the smallest lectin with much less immunogenicity than other members of the lectin family. In this study, to improve nose-to-brain drug delivery and reduce the immunogenicity of traditional lectin modified delivery system, OL was conjugated to poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles and its biorecognitive activity on nanoparticles was verified by haemagglutination tests. Nose-to-brain delivery characteristic of OL-conjugated nanoparticles (OL-NP) was investigated by in vivo fluorescence imaging technique using DiR as a tracer. Besides, urocortin peptide (UCN), as a macromolecular model drug, was incorporated into nanoparticles and evaluated for its therapeutic efficacy on hemiparkinsonian rats following intranasal administration by rotation behavior test, neurotransmitter determination and tyrosine hydroxylase (TH) test. The results suggested that OL modification increased the brain delivery of nanoparticles and enhanced the therapeutic effects of UCN-loaded nanoparticles on Parkinson's disease. In summary, the OL-NPs could be potentially used as carriers for nose-to-brain drug delivery, especially for macromolecular drugs, in the treatment of CNS disorders.