A nanophytosomes formulation based on elderberry anthocyanins and Codium lipids to mitigate mitochondrial dysfunctions
Daniela Mendes, Patrı́cia Valentão, Maria Manuel Oliveira, Paula B. Andrade, Romeu A. Videira
Abstract
The development of nanomedicines to modulate the mitochondrial function is a great scientific challenge since mitochondrial dysfunction is a pathological hallmark of many chronic diseases, including degenerative brain pathologies like Parkinson's and Alzheimer's diseases. To address this challenge, the mitochondriotropic features of the elderberry anthocyanin-enriched extract (Sambucus nigra) were combined with the self-assembling properties of the membrane polar lipids from Codium tomentosum in an innovative SC-Nanophytosomes formulation. Membrane polar lipids, obtained by a new procedure as chlorophyll-free extract, are characterized by 26% of non-phosphorus polar lipids and 74% of phospholipids (dominated by anionic lipids) containing a high degree of polyunsaturated fatty acids. The anthocyanin-enriched extract is dominated by a mixture of four cyanidin-glycosides, representing about 86% of their phenolic content. SC-Nanophytosomes engineered with 600 µM algae membrane polar lipids and 0.5 mg/L of the anthocyanin-enriched extract are nanosized vesicles (diameter =108.74 ± 24.74 nm) with a negative surface charge (Zeta potential = -46.93 ± 6.63 mV) that exhibit stability during storage at 4 ºC. In vitro assays with SH-SY5Y cells showed that SC-Nanophytosomes have the competence to target mitochondria, improving the mitochondrial respiratory chain complexes I and II and preserving the mitochondrial membrane potential in the presence of rotenone. Additionally, SC-Nanophytosomes protect SH-SY5Y cells against the toxicity induced by rotenone or glutamate. Green-fluorescent labeled SC-Nanophytosomes were used to reveal that they are mainly internalized by cells via caveola-mediated endocytosis, escape from endosome and reach the cytoplasm organelles, including mitochondria. Overall, data indicate that SC-Nanophytosomes have the potential to support a mitochondria-targeted therapy for neurodegenerative diseases.