posted on 2023-09-20, 05:03authored byNikolina Kalčec, Nikolina Peranić, Ivan Mamić, Maja Beus, Christopher R. Hall, Trevor A. Smith, Marc Antoine Sani, Petra Turčić, Frances Separovic, Ivana Vinković Vrček
The development of efficient drug formulations for Parkinson’s
disease (PD) treatment is challenged by achieving pharmacokinetic
profiles, reduced side effects, and better permeability through the
blood–brain barrier (BBB). As nanoparticles may facilitate
the delivery of drugs in the brain due to their high-loading capacity
and ability to cross biological barriers, we designed two different
types of selenium nanoparticles (SeNPs) that may increase the transport
of drugs across the BBB and may act as antioxidants at the site of
action. The SeNPs were functionalized with polyvinylpyrrolidone (PVP)
and polysorbate 20 (Tween) and characterized in terms of their size,
size distribution, shape, surface charge, and colloidal stability
in relevant biological media. Their drug-loading capacity was tested
using dopamine and l-DOPA as therapeutically active agents
for PD. Thermodynamic analysis revealed that binding processes occurred
spontaneously through hydrogen bond/van der Waals interactions or
electrostatic interactions. The strongest interaction was observed
between PVP-SeNPs and l-DOPA or dopamine, which was characterized
by a binding constant several orders of magnitude higher than for
Tween-SeNPs. However, the addition of human transferrin as a model
plasma protein significantly reduced this difference, which indicates
the crucial role of protein corona formation in the design of drug
nanodelivery systems. In vitro evaluation by cell-free
and cellular transwell models showed efficient internalization of
SeNP-loaded l-DOPA/dopamine by human endothelial brain cells,
while facilitated BBB permeability for l-DOPA, and dopamine
was achieved using PVP-SeNPs. Overall, the high potential of SeNPs
as drug-delivery vehicles in PD treatment was demonstrated.