Use of Active Salmon-Lecithin Nanoliposomes to Increase Polyunsaturated Fatty Acid Bioavailability in Cortical Neurons and Mice

Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play an important role in the development, maintenance, and function of the brain. Dietary supplementation of n-3 PUFAs in neurological diseases has been a subject of particular interest in preventing cognitive deficits, and particularly in age-related neurodegeneration. Developing strategies for the efficient delivery of these lipids to the brain has presented a challenge in recent years. We recently reported the preparation of n-3 PUFA-rich nanoliposomes (NLs) from salmon lecithin, and demonstrated their neurotrophic effects in rat embryo cortical neurons. The objective of this study was to assess the ability of these NLs to deliver PUFAs in cellulo and in vivo (in mice). NLs were prepared using salmon lecithin rich in n-3 PUFAs (29.13%), and characterized with an average size of 107.90 ± 0.35 nm, a polydispersity index of 0.25 ± 0.01, and a negative particle-surface electrical charge (−50.4 ± 0.2 mV). Incubation of rat embryo cortical neurons with NLs led to a significant increase in docosahexaenoic acid (DHA) (51.5%, p < 0.01), as well as palmitic acid, and a small decrease in oleic acid after 72 h (12.2%, p < 0.05). Twenty mice on a standard diet received oral administration of NLs (12 mg/mouse/day; 5 days per week) for 8 weeks. Fatty acid profiles obtained via gas chromatography revealed significant increases in cortical levels of saturated, monounsaturated, and n-3 (docosahexaenoic acid,) and n-6 (docosapentaenoic acid and arachidonic acid) PUFAs. This was not the case for the hippocampus or in the liver. There were no effects on plasma lipid levels, and daily monitoring confirmed NL biocompatibility. These results demonstrate that NLs can be used for delivery of PUFAs to the brain. This study opens new research possibilities in the development of preventive as well as therapeutic strategies for age-related neurodegeneration.

Transfer Phenomena of Nanoliposomes by Live Imaging of Primary Cultures of Cortical Neurons

“…The particle mean size was found to be 103.5 ± 1.5 nm ( n = 3). These NL contain multiple bilayers and the NL’s size was further confirmed via transmission electron microscopy (TEM) that also confirmed their spherical morphology ( Figure 1 C), as previously shown [ 14 , 15 , 32 , 33 ].…”

“…Results showed that salmon lecithin was composed primarily of phospholipids (67.65 ± 0.90%), then triglycerides (31.20 ± 0.40%) and a low level of total cholesterol (1.15 ± 0.10%), ( n = 10). Phosphatidylcholine (PC) was the most abundant class of total phospholipids (42%) [ 15 ]. Hence, although salmon lecithin was found to be composed primarily of phospholipids, it contains neutral lipids and a low level of total cholesterol.…”

“…Recent results have demonstrated the neurotrophic effects of NL in an in cellulo model as well as their bioavailability in vivo [ 14 , 15 ]. Nevertheless, little information is available on NL interaction with neurons and the mechanisms of internalization involved at the cellular level.…”

“…We recently demonstrated, for the first time, the bioavailability of NL PUFA in neuronal cell culture and mouse models, with a higher enrichment in n-3 PUFA after administration of NL at the cerebral level, in particular in the cortex, compared with the peripheral tissues (liver). In addition, these naturally-derived NL have been shown to be biocompatible in vivo [ 15 ].…”

Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA

“…We used the salmon-derived Lip, which are an intriguing type of Lip because they present a double functionality, since they are rich in bioactive ω-3 and ω-6 polyunsaturated fatty acids, and they can encapsulate bioactive molecules [33][34][35][36]. Lip were enzymatically extracted from salmon fish heads and EVs were isolated from neonatal rat cardiac fibroblasts (CFs)s culture media and used to produce loaded hELs via incubation followed by probesonication as shown in figure 1(A) [35,37,38].…”