Steric stabilisers govern the colloidal and chemical stability but not in vitro cellular toxicity of linoleoylethanolamide cubosomes

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 192; p. 111063
• Main Authors: Mohammad, Younus, Fallah, Anita B., Reynolds, John N.J., Boyd, Ben J., Rizwan, Shakila B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2020
• Subjects: bicontinuous cubic phase; blood-brain barrier; cubosomes; Linoleoylethanolamide; liquid crystals; Pluronic F127; Pluronic F68; stabilisers; Tween 80; blood-brain barrier; Pluronic F68; Pluronic F127; cubosomes; liquid crystals; Linoleoylethanolamide; stabilisers; Tween 80; bicontinuous cubic phase
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2020.111063

[Display omitted] •Effect of Tween 80 on stability and structure of LEA dispersions was investigated•Effect of Pluronics on stability and structure of LEA dispersions was investigated•Pluronics were more effective in stabilising LEA dispersions compared to Tween 80•LEA was chemically unstable in the presence of Tween 80 upon storage Linoleoylethanolamide (LEA) is an endogenous lipid with remarkable neuromodulatory properties. However, its therapeutic potential is limited by rapid clearance in vivo, targetability and solubility. This study aimed to formulate LEA into liquid crystalline nanoparticles (cubosomes) as a strategy to address the aforementioned challenges. The influence of three different steric stabilisers: Tween 80 and Pluronic F68, both of which have the potential to interact with receptors expressed at the blood-brain barrier and Pluronic F127 as a control, on colloidal stability, internal structure, chemical stability and cytotoxicity of the dispersions were investigated. We found that for effective stabilization of LEA dispersions, a higher concentration of Tween 80 was required compared to Pluronics. Freshly prepared dispersions showed mean particle size of <250 nm and low PDIs (<0.2), with an Im3m type cubic structure but with different lattice parameters. Upon storage at ambient temperature for a week, increased mean particle size and PDI, with a significant reduction in the concentration of LEA was observed in Tween 80-stabilised dispersions. Greater than 80% cell viability was observed at concentrations of up to 20 μg/mL LEA in the presence of all three stabilisers. Collectively, our results suggest that the stabiliser type influences colloidal and chemical stability but not cytotoxicity of LEA cubosomes. This study highlights the potential of endogenous bioactive lipids to be utilized as core cubosome forming lipids with the view to improving their solubility, rapid clearance and targetability to enable delivery of these bioactive molecules to the brain.