Solid lipid nanoparticles as carriers for Ulva rigida peptide extract with demonstrated anti-β-amyloid and antioxidant properties

Tânia Sofia Granja Tavares^*Iva CarvalhoMaria João RamalhoStéphanie AndradeMaria Do Carmo Pereira^*Joana A. Loureiro^*

• LEPABE, Faculty of Engineering, University of Porto, Porto, Portugal

Alzheimer's disease (AD) remains one of the greatest challenges in neurodegenerative research, largely due to the toxic aggregation of the β-amyloid (Aβ) peptide and the difficulty of delivering therapeutic compounds across the blood-brain barrier (BBB). This work explored Ulva rigida (U. rigida), a green macroalga rich in bioactive peptides, as a natural source of anti-amyloidogenic and antioxidant agents. First, the peptides extraction process was optimized by design of experiments (DoE). Peptides extracted and hydrolyzed under optimized conditions showed antioxidant capacity (2.51 ± 0.18 μmolTrolox equivalent/ mghydrolyzed protein), and the fraction of peptides with a molecular weight lower than 3 kDa was able to reduce the aggregation of Aβ₁₋₄₂ peptide in vitro by around 60%. To overcome the issue of limited bioavailability, we encapsulated these peptides in solid lipid nanoparticles (SLNs). The developed nanoformulation displayed a size of 158 ± 14 nm, narrow polydispersity, and near-neutral zeta potential (-4.7 ± 0.6 mV), with an encapsulation efficiency (EE) of 54.1 ± 0.1% and suitable stability under simulated gastrointestinal and storage conditions. By combining biological activity with a delivery platform, this study highlights the potential of Ulva rigida peptides as a promising source of bioactive peptides candidate with the potential to delay thefor further preclinical evaluation for delaying the onset or progression of AD..