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

Abstract

Soft nanoparticles, and in particular, nanoliposomes (NL), have attracted increasing interest for their use in food, nutraceuticals, and in particular, in pharmaceutics for drug delivery. Recent data using salmon lecithin NL suggest that these NL, rich in omega-3 (n-3) fatty acids, can improve the bioavailability and transport of molecules through the blood brain barrier (BBB) to target the brain for the prevention and treatment of neurodegenerative diseases. The objective of this study was to characterize the physicochemical properties and analyze the transfer phenomena of salmon lecithin NL over time in neurons to better understand the behavior of NL in an intracellular environment. To test this, primary cultures of cortical neurons from rat embryos were incubated with salmon lecithin NL from day 3 after cell culture, for up to 104 h. The physicochemical properties of NL such as size, speed, morphology and the diffusion coefficient in the live cultures, were studied over time. Image analysis of cell morphology showed dendritic growth and neuronal arborization after 48 h of exposure to NL, for up to 104 h. Results showed an NL stability in size, speed and diffusion coefficient over time, with a peak at 48 h, and then a return to baseline value at the end of incubation. The average speed and diffusion coefficient achieved provided important information on the mode of entry of NL into neurons, and on the slow diffusion rate of NL into the cells. Analysis of videos from 2 h to 104 h showed that significant levels of NL were already internalized by neurons after 3 h incubation. NL appearance and intracellular distribution indicated that they were packed in intracellular compartments similar to endocytic vesicles, suggesting internalization by an active endocytic-like process. The results obtained here demonstrate internalization of NL by cortical neurons by an active endocytic-like process, and suggest the potential use of NL for time-release of therapeutics aimed towards prevention or treatment of neurodegenerative diseases.

Neuroprotective Effect of Curcumin-Loaded RGD Peptide-PEGylated Nanoliposomes

“…We previously showed that NL particles can be internalized by neurons through a process resembling endocytosis [ 13 ]. We would thus propose that upon exposure to neurons, the curcumin-loaded NL formulations were internalized, allowing direct access to curcumin intracellularly.…”

“…Lecithin was extracted and purified from the heads of Salmo salar (Atlantic salmon) using a low-temperature enzymatic hydrolysis without any organic solvents [ 13 ]. Chloroform, methanol, and Dulbecco’s phosphate-buffered saline (DPBS) were purchased from Thermo Fisher Scientific (Ref: 14190144, Gibco, Massy, France).…”

“…Oral administration of these NL to mice led to an enrichment in PUFAs in their brains without significant weight gain or hepatic lipid accumulation, indicating the potential use of ω-3 PUFA-rich NL for delivery of PUFAs to the brain. Moreover, cell culture studies demonstrated the neurotrophic effects of NL in the primary culture of rat embryo neurons, which were able to internalize NL by a process resembling endocytosis [ 13 ]. By virtue of its properties, NL can be used to encapsulate both hydrophilic and hydrophobic molecules.…”

Ischemic Brain Injury: Involvement of Lipids in the Pathophysiology of Stroke and Therapeutic Strategies

“…Positive outcomes highlight the efficiency of lipid nanoparticles and nanostructured lipid carriers to target the brain and protect against ischemic stroke [ 161 , 162 , 163 ]. The intranasal route of PUFAs or other drug delivery via lipid nanoparticles is also very promising, allowing the drug to directly reach the brain by bypassing the blood–brain barrier, a structure that restricts the passage of therapeutic agents and limits the efficacity of the delivery [ 164 , 165 , 166 , 167 ].…”

Functionalized liposomes for targeted breast cancer drug delivery

“…Liposomes, first introduced in 1965, are rounded vesicles composed of either single or multiple lipid bilayers with an aqueous center [ [48] , [49] , [50] ]. These vesicles can spontaneously form when amphiphilic lipids, such as phospholipids, are dispersed in water and closely resemble our cellular membranes [ 51 , 52 ]. This similarity serves as an immense advantage for drug delivery in terms of biocompatibility and biodegradation.…”