Mesalamine and fucoxanthin co-loaded SNEDDS for neuroprotection in Parkinson’s disease

Parkinson’s (PD) disease is a progressive neurodegenerative disorder characterized by impaired movement due to diminished dopamine levels. Self‑nanoemulsifying drug delivery systems (SNEDDS) offer a favorable approach to elevating the bioavailability of poorly water‑soluble anti‑Parkinsonian agents by increasing their solubility, intestinal uptake, and brain delivery. In this work, we developed and optimized an SNEDDS co‑encapsulating Mesalamine and Fucoxanthin as a potential PD therapy. A central composite design was utilized to inspect how the proportions of liquid lipid, surfactant, and co‑surfactant affected critical quality attributes, namely particle size, zeta potential, polydispersity index, and drug loading. Perturbation plots and three‑dimensional response surfaces were then used to visualize the effects of these formulation variables. Optimized Mesalamine–Fucoxanthin SNEDDS exhibited an average particle diameter of 156.45 ± 26.8 nm, a surface charge of −20.89 ± 6.04 mV, a PDI of 0.33, and drug‑loading efficiencies of 93.81 ± 1.75% (Mesalamine) and 88.32 ± 1.33% (Fucoxanthin), all of which met the predefined acceptance criteria. Transmission electron microscopy (TEM) confirmed that the particles were spherical in shape and under 200 nm, in agreement with dynamic light‑scattering results. In vitro cytotoxicity study evaluated by MTT assay in SH‑SY5Y cells showed over 95% viability after 24 h, indicating that the formulation is biocompatible. In addition to this, Mesalamine-Fucoxanthin SNEDDS significantly suppressed the production of inflammatory markers, showing 1.6-fold and 3.25-fold depletion in IL-6 and TNF-α, respectively, at a concentration of 10 µg/mL, as contrasted to the inflammation-induced group.