Abstract
After more than fifty years, the administration of levodopa (LDOPA), a
prodrug that crosses the blood-brain barrier and is metabolized to
dopamine in the central nervous system, remains the most effective
treatment for Parkinson's disease, despite the manifestation of
significant side effects. The development of carrier systems to increase
the rate of LDOPA crossing the blood-brain barrier, to achieve stable
therapeutic plasma levels and minimize side effects, has been a
challenge. Innovative nanosystems for delivering LDOPA are being tested
for improved Parkinson's disease therapy. In particular,
buckminsterfullerene C-60 is promising, due to its ability to penetrate
through the skin and the gastrointestinal tract, as well as its
biomedical applications to enhance drug delivery. Aiming to give
theoretical support to attempts in developing levodopa preparations for
transdermal and oral administration that may provide more continuous
dopamine stimulation and fewer side effects, we present a computational
study of levodopa adsorption on C-60 fullerene in the 2-8 pH range. The
LDOPA state with COO- and NH3+ protonated (LDOPAc) is investigated, with
classical molecular dynamics (CMD) and density functional theory (DFT)
simulations being undertaken to describe the LDOPAc adsorption onto C-60 fullerene, LDOPAc@C-60. Annealing calculations were performed to explore the space of molecular configurations of LDOPAc@C-60 to obtain optimal
geometries. From the DFT simulations, we found a four-level adsorption
pattern, which is in agreement with the shell distribution of LDOPAc
around C-60 that we have obtained from our CMD simulations. Four van der Waals-like interaction potentials, characteristic of the LDOPAc@C-60
adsorption levels were estimated, each one related to an -OH group, with
energy minima varying from -0.35 eV to -0.73 eV, and centroid-centroid
distances in the 6.5-8.8 angstrom range. Infrared absorption and Raman
scattering spectra of the four adsorption configurations were evaluated,
allowing us to determine vibrational signatures, which can be very
useful in probing the existence of the four adsorption levels.
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