Analysis of Targeted Therapy of Parkinson’s Disease with Coloaded Nanoparticles

Abstract

The key to the treatment of Parkinson’s disease (PD) is delivering an effective amount of drugs into the brain to work, and supplementing the missing dopamine (Dop) in the brain is still the most effective treatment currently. In this research, borneol (Bor) was utilized to promote the drug to enter the brain through the nasal cavity, and lactoferrin (Lf) was utilized as the targeting molecule to modify the nanoparticles (NPs) so that they entered the brain and focused on the lesion site of PD to achieve targeting. They were then evaluated in vivo and in vitro , thus providing the basis for the development of the Lac-Bor/Dop NPs in PD therapy. In the experiment, the particle size of Lac-Bor/Dop NPs prepared by the optimal prescription process was 163.7±15.6 nm, the Dop drug loading was (7.86±1.68) %, and the Zeta potential was (−21.36±3.34) mV. The in vitro release confirmed that the Lac-Bor/Dop NPs had good sustained release characteristics in PBS medium. The cytotoxicity and uptake experiments confirmed that the cytotoxicity of Dop encapsulated in NPs was markedly inferior to that of free Dop ( P <0.05). For SH-SY5Y cells and 16HBE cells, Bor and Lf co-modified NPs can promote cell uptake. In vivo animal imaging counts confirmed that the coloaded NPs were capable of synergistic nasal drug delivery to the brain for better brain targeting. Furthermore, a PD model induced by dopaminergic neuron injury induced by unilateral striatal injection of 6-OHDA was constructed in rats and assigned into various groups to demonstrate the therapeutic effect of NPs on PD rats. The results revealed that relative to other groups, the contralateral rotations of rats in the Lac-Bor/Dop NP group were decreased drastically after 20 days of administration ( P <0.01), and the levels of Dop and dihydroxyphenylacetic acid (DOPAC) in the injured striatum were increased markedly ( P <0.01), demonstrating that the delivery system could achieve excellent PD therapy effects after nasal administration.