The administration of levodopa/carbidopa, prodrugs that cross the blood–brain barrier and are metabolized to dopamine in the central nervous system, remains the most effective treatment for Parkinson’s disease. The development of carrier systems to increase the rate of blood–brain barrier crossing has been a challenge. In particular, buckminsterfullerene C60 is promising, due to its ability to penetrate through the skin and the gastrointestinal tract. Aiming to give theoretical support to attempts in developing levodopa/carbidopa preparations for transdermal and oral administration looking for more continuous dopamine stimulation, we present a computational study of them adsorbed on C60 fullerene in the 2–8 pH range. We use classical and quantum simulations as our computational tools. Annealing calculations were performed to explore the space of their molecular configurations to obtain optimal geometries. A detailed interpretation of their harmonic vibrational frequencies are also presented, through the analysis of their Raman and infrared spectra.

Ascorbic acid (AsA) and the nonsteroidal anti-inflammatory drug ibuprofen (IBU), adsorbed noncovalently on buckminsterfullerene C60 for its transdermal delivery, are investigated using Classical Molecular Dynamics and Density Functional Theory. Classical annealing is performed to explore the molecular configurations of both AsA and IBU adsorbed on C60, searching for optimal geometries. In particular, it is shown that IBU assumes two distinct adsorption geometries, giving rise to a two-level adsorption, leading to an extended anti-inflammatory delivery time. A vibrational analysis was also carried out for adsorbed IBU, depicting the IR and Raman spectra for both geometries. Furthermore, we investigated also the binding of IBU to human serum albumin (HSA) by using a fragmentation strategy together with a dispersion corrected exchange–correlation functional. Our computer simulations are valuable for a better understanding of the binding mechanism of AsA and IBU, looking for rational design and the development of novel drugs with improved potency.