Parkinson Hastalığının Etkinliğini Geliştirmek için Beyin Hedefli Protocells Kullanan Levodopa ve Curcumin'in Birlikte Yüklenmesi

Parkinson's disease (PD), one of the most common movement and neurodegenerative disorders, is challenging to treat. Levodopa is a common clinical drug for controlling the symptoms of PD, but it only replenishes the missing dopamine, can’t protect dopaminergic neurons. While curcumin as a neuroprotective agent has been reported for treatment of PD. Herein, we present a novel organic-inorganic composite nanoparticle with brain targeting (lf-protocells) for co-delivery of levodopa and curcumin, and demonstrate its attractive use as a biocompatible platform for PD treatment. The nanoparticle system is comprised of a lactoferrin (lf) modified lipid bilayer (LB) containing curcumin as its outer membrane and mesoporous silica nanoparticles (MSNs) containing levodopa as its supporting inner core. Our studies illustrate that the lf-protocells have a spherical morphology, and can be used to co-load levodopa and curcumin efficiently; the combination of curcumin and levodopa alleviates the apoptosis of PD cells, decreases the expression of a-synuclein and increase the expression of tyrosine hydroxylase in SH-SY5Y cells as compared to single drug; the binary-drug loaded lf-protocells ameliorate oxidative stress and mitochondrial dysfunction as compared to combination of free drugs; lf-protocells improve significantly the distribution in brain compared with unmodified protocells; binary-drug loaded lf-protocells have better performance of motor function in mouse than unmodified protocells and combination of free drugs. In conclusion, binary-drug loaded lf-protocells show better therapeutic efficacy in both cell model and mouse model of PD than combination of free drugs and lower toxicity than bare MSNs. These results suggest that lf-protocells can be used as a promising drug delivery platform for targeted therapy against PD and other diseases of the central nervous system.