Trehalose is a bisacetal, non-reducing homo-disaccharide in which two glucose units are linked together via a α-1,1-glycosidic bond, often considered the gold standard for cryoprotection [92, 114]. It is commonly found amongst organisms capable of withstanding extreme drought and cold in nature e.g. water bear and yeast, whereas mammalian cells unfortunately lack the mechanism to synthesise trehalose endogenously [115]. The ability of trehalose to produce a better cyroprotective effect in terms of the water replacement hypothesis has been attributed to the absence of internal hydrogen bonds. Therefore, this enables a more flexible formation for hydrogen bonds to form with nanoparticles, so that their functional conformation can be retained …show more content…
It is the most abundant disaccharide in the biological world, synthesised by plants and other oxygenic photosynthetic organisms, but principally obtained from the juice of sugar cane and sugar beets [117, 118]. Sucrose possesses many comparable characteristics to trehalose for its use as a cryoprotectant, including being chemically innocuous, hydrophilic, having a low hygroscopicity and having a positive influence on the glass transition temperature [90]. However, L. Zhang et al. [105] showed sucrose displayed the largest increase in particle size and distribution compared to the four other cryoprotectants studied. Although despite this, in a study by M. Holzer et al. [90] the ability of sucrose in maintaining particle size following reconstitution after freeze drying was expressed, with the initial size (162.1 ± 0.8 nm) remaining almost unaffected after freeze-drying (162.7 ± 1.1 nm). This was reiterated in a study carried out by P. Fonte et al. [72] showing that sucrose maintained the particle size of the insulin loaded nanoparticles after freeze-drying, whilst maintaining the overall zeta