Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson's disease

Drug Deliv. 2019 Dec;26(1):700-707. doi: 10.1080/10717544.2019.1636420.

Abstract

Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC0-12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p < .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson's disease.

Keywords: Dopamine; Parkinson’s disease; borneol; lactoferrin; nose-to-brain targeted nanoparticles.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / pharmacokinetics
  • Antiparkinson Agents / pharmacology
  • Brain / metabolism*
  • Camphanes*
  • Cells, Cultured
  • Dopamine / administration & dosage*
  • Dopamine / pharmacokinetics
  • Dopamine / pharmacology
  • Drug Delivery Systems
  • Lactoferrin*
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Parkinson Disease / drug therapy
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antiparkinson Agents
  • Camphanes
  • Lactoferrin
  • isoborneol
  • Dopamine

Grants and funding

This work was supported by the Natural Science Foundation of Shandong Province (ZR2017LH076 and ZR2018ZC1055).