A nanophytosomes formulation based on elderberry anthocyanins and Codium lipids to mitigate mitochondrial dysfunctions

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 mu M 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 degrees C. 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.

Automated summary

The innovative SC-Nanophytosomes developed with mitochondriotropic elderberry anthocyanin-enriched extract and self-assembling membrane polar lipids from Codium tomentosum show potential in targeting mitochondria and improving mitochondrial function, as well as enhancing cellular resistance to toxins.