Cholesterol has been widely utilized in nanoliposomes as a primary component. The inclusion of cholesterol in liposomes increases the membrane rigidity and limits the conformational alterations in the liposomal bilayer and eventually, decreases the rate of bioactive compound release, especially for hydrophilic compounds. In order to limit cholesterol usage, the replacement of cholesterol with plant sterols have also been considered in nanoliposome formulations. Plant sterols increased both the encapsulation of ascorbic acid (i.e., a hydrophilic solute) and the mean diameter of liposomes, therefore fine tuning of production methods would need to be carried out (Alexander, Lopez, Fang, & Corredig, 2012).
Similar to cholesterol, certain other compounds, such as phenolic compounds, have a bearing on the encapsulation, physical properties, and delivery characteristics of nanoliposomes (Demirci, Caglar et al., 2017). The variations in the structures of phenolic compounds can also be anticipated to alter encapsulation and stability characteristics of liposomal dispersions. In the case of tea catechins, e.g., the presence of gallic acid esters enhanced the affinity of EGCG molecules to the lipid/liposomal bilayers and induced the incorporation of significant amounts of polyphenols in the bilayers (Nakayama, Hashimoto, Kajiya, & Kumazawa, 2000). That also affected the membrane fluidity and morphology (Ikigai, Nakae, Hara, & Shimamura, 1993). The presence of catechins in the membranes enhanced the rigidity of cellular membranes as well. All these findings pointed out to liposomal encapsulation and stabilization of phenolic compounds.
The solvents applied in nanoliposome preparation (i.e., thin film hydration, solvent injection methods, etc.) also deeply affect the basic characteristics and liposomal performance. For example, methanolic extracts of polyphenols from cyanobacteria and algae were more concentrated in terms of polyphenol content compared to ethanolic extracts, whereas the encapsulation efficiency of the ethanolic extracts was found to be higher (de Assis, Machado, da Motta, Costa, & de Souza-Soares, 2014). However, in the context of food products and nutraceuticals, the extent of solvent and surfactant usage has to be clearly limited (i.e., toxicity, irritancy, etc.). Also at high surfactant concentrations, vesicle size growth and bilayer solubilization might take place (Alonso, Villena, & Gobi, 1981) which could rupture liposomal structures and render the encapsulation process unsuccessful.