Perfluoroalkylated fatty acid monoesters of trehalose and sucrose for biomedical applications: Remarkable emulsifying properties of 6‐O‐[3′‐(perfluorooctyl) propanoyl]‐trehalose

Abstract

A new series of perfluoroalkylated fatty acid monoesters of a,~trehalose and sucrose has been evaluated with respect to their physicochemical and biological properties for possible biomedical use. These water-soluble compounds strongly reduce the water surface tension and fluorocarbon/water interracial tension. As cc~surfaetants in perfluorodecalin/Pluronic F4}8 type emulsions they significantly increase the stability of these emulsions. Remarkably stable concentrated perfluorodee~qlin-in-water (50% w/v) emulsions were obtained when the CsF]TCH2CH2C(O~a,a-trehalose monoester was used as the sole surfaetant, while no emulsion could be obtained with its maltoside analogue. No significant effect on the growth and viability of Namalva cell cultures and no hemolytic activity on human erythrocytes at concentrations up to 50 g/L were detected for these amphiphiles in spite of their high surface activity. The LDs0 was found to be in the range of 250-375 mg/kg of body weight Lv. in mice.KEY WORDS: Fluorocarbon emulsion, perfluorodecalin emulsion, perfluoroalkylated fatty acid monoester of sucrose, perfluoroalkylated fatty acid monoester of trehalose, perfluoroalkylated stu ~ factant, 6-O-[3'-(perfluorooctyl) propanoyl]-trehalose.

Hydrophobic tail length, degree of fluorination and headgroup stereochemistry are determinants of the biocompatibility of (fluorinated) carbohydrate surfactants

“…For example, the haemolytic activity of short-chain surfactants (C 8 to C 12 ) decreases with decreasing size of the carbohydrate headgroup (disaccharide > monosaccharide headgroup) and flexibility of the headgroup (pyranoside > straight polyhydroxylated chain), but increases with increasing tail length [1, 33]. In contrast, a fluorinated tail protects against haemolysis, with high micromolar or low millimolar concentrations typically displaying no haemolytic activity [10, 12, 34]. In agreement with these earlier studies, maltopyranosides displayed more haemolytic activity compared to gluco- and galactopyranosides and a fluorinated tail protected against haemolysis by β-glucopyranosides and maltopyranosides.…”

Synthesis and biocompatibility evaluation of fluorinated, single-tailed glucopyranoside surfactants

“…This is in contrast to the positive control, octylthioglucoside (OTG), which showed significant cytotoxicity over the same concentration range. Similarly, partially fluorinated surfactants derived from maltose, 47 mannitol, 48 sorbitan, 48 sucrose, 49 trehalose, 49 and xylitol 50 also display moderate-to-low toxicity in cells in culture, with EC 50 typically 4100 mM. In contrast, glucopyranosides with shorter fluorinated chains (r12 carbon atoms) appear to be more cytotoxic than glucopyranosides 8a-f. 25 For example, 7,7,8,8,9,9,10,10,11,11,12,12,12-tridecafluorododecyl-b-D-glucopyranoside was cytotoxic at concentrations of 50 mM.…”

“…Similar observations have been reported for various other fluorinated surfactants. 5,12,[47][48][49][50] In addition, the haemolytic activity decreased for structurally related glucopyranosides (i.e., 8a-d with ten and 8d-f with eleven methylene groups in the hydrocarbon spacer) with increasing Table 2 Assessment of cytotoxicity and haemolytic activity of partially fluorinated glucopyranosides and their hydrocarbon analogues in the B16F10 cell line. 12,46 Haemolytic activity, EC length of the perfluoroalkyl terminus.…”

Synthesis, emulsification and self-assembly properties of sugar-containing semifluorinated amphiphiles

“…sugar phosphates, amino sugars, etc), and have been used to prepare emulsions of perfluorocarbons. 12-16 Our goal was two-fold – first, it was to investigate the use of saccharide-perfluoroalkyl amphiphiles with respect to the sevoflurane-perfluorooctyl bromide system, and second, it was to explore convenient methods of introducing a perfluoroalkyl chain into a saccharide-based hydrophilic head. Perfluoroalkyl chains have been installed into saccharides by a number of different chemistries: glycosylation, 17-22 formal glycosylation, 23-24 ether formation, 13,14,25 ether formation by way of radical addition, 14,26 acetal formation, 27 carbon-carbon bond formation, 28 urea, 29,30 thiourea 29,31 and carbamate 32 formation, phosphoester formation, 33-35 ester 15,26,36 and amide 23,37-39 formation, as well as thiol-initiated Michael 40 and free radical 41 addition.…”