Self‐Assembled Nanocarriers of Synthetic and Natural Plasmalogens for Potential Nanomedicine Development

Abstract Plasmalogens are bioactive glycerophospholipids with a vinyl ether bond at the sn‐1 position of the glycerol backbone, which imparts free‐radical scavenging properties. Amelioration of the plasmalogen levels, which decline with aging, is required for novel metabolic therapies for Parkinson's disease (PD), Alzheimer's disease (AD), and dementia. This work designed, prepared, and in vitro characterized plasmalogen‐loaded lipid nanoparticles with neuroprotective potential for neuronanomedicine. Liquid crystalline nanoparticles formed by natural scallop‐derived plasmalogens are in vitro evaluated with respect to synthetic docosapentaenoyl (DPA) plasmenyl (vinyl ether) glycerophospholipids, formulated with the helper lipid monoolein (MO). The structural organization of the lipid nanoparticles is characterized by synchrotron small‐angle X‐ray scattering (SAXS). The employed self‐assembly technique yielded plasmalogen‐based nanoassemblies of hexosome, cubosome, vesicular, or intermediate topology types. The internalization of fluorescently‐labeled nanoparticles in differentiated human neuroblastoma SH‐SY5Y cells is followed by flow cytometry. Under the investigated conditions, the scallop‐derived plasmalogen nanocarriers significantly influenced the measured mitochondrial membrane potential compared to those involving synthetic plasmalogens with DPA chains. Levels of protein biomarkers, such as brain‐derived neurotrophic factor (BDNF), can be regulated depending on the nanocarrier type. The results identified cubosome, hexosome, and vesicular types of plasmalogen nanocarriers presenting antioxidant properties and preserving neuronal cell integrity and viability.