Development of an Auraptene-Loaded Transdermal Formulation Using Non-ionic Sugar Ester Surfactants.

Auraptene (Aur) is a naturally occurring monoterpene coumarin ether that exhibits numerous therapeutic properties. Its high lipophilicity and low skin penetration, however, limit its potential application for local and transdermal delivery. Biocompatible non-ionic sugar esters (SEs) possess beneficial properties for the development of transdermal formulations in delivering pharmaceutically challenging molecules such as graphene and Aur. In the present study, we conducted a series of experiments to demonstrate the effect of several previously unstudied SEs on the skin permeation and distribution of Aur by preparing gel- and dispersion-type formulations. Skin permeation and deposition experiments were conducted using a Franz diffusion cell with rat skin as the membrane. The dispersion-type formulations prepared using SEs had higher entrapment efficiency, as well as better skin permeation and retention profiles. The dispersion-type formulation containing sucrose palmitate (sSP) exhibited the highest skin permeation over 8 h. Notably, the enhancement effects on Aur concentration in full-thickness skin after the application of the dispersion-type formulation was higher than those of the control formulation. These results indicated that the prepared formulation has potential for use in the transdermal delivery of Aur in pharmaceutical and cosmetic products.

Aqueous Sugar-Based Amphiphile Systems: Recent Advances in Phase Behavior and Nanoarchitectonics.

Currently, numerous fascinating molecular assemblies are used in food, cosmetics, and pharmaceuticals. Sugar-based amphiphiles are representative constituents of these molecular assemblies. Despite numerous studies on these generic compounds, many aspects remain unexplored even in aqueous systems. In this review, molecular assembly studies of sugar-based amphiphiles in aqueous systems are summarized. First, recent advances in molecular assembly studies, including the glassy state of lyotropic and thermotropic liquid crystalline (LC) phases, modulated crystal phases, and coagels consisting of nanofibers of alkyl ß-D-glycosides, are presented. Second, research on thermotropic LC phases under desiccated conditions of trehalose fatty acid monoesters to clarify the fundamental behaviors of the glassy state and their use as stabilizers of glass-forming surfactants for pharmaceutical applications are discussed. Several effective X-ray analytical approaches are included to identify or clarify these phenomena, unknown or unsolved for a long time. Third, a comprehensive analysis of vitamin E (tocopherol)-cyclodextrin in aqueous systems is presented. Along with these topics, the importance of investigating stabilizer-free functional components, considered minor components, is highlighted. These unveiled phenomena or concepts will contribute to the development of nanoarchitectonics covering the self-assembly and selforganization of soft molecules.

The useful biological properties of sucrose esters: Opportunities for the development of new functional foods.

Sucrose esters have been deployed as surfactants in many food products since the 1950s. In addition to their useful physical characteristics, sucrose esters also have interesting biological properties that enhance their utility. This review critically examines the broad suite of biological activities that has been attributed to both synthetically-derived and naturally-occurring sucrose esters. These include insecticidal, molluscicidal, plant growth-regulating, anti-microbial, anti-tumor, anti-oxidant, anti-depressive, neuro-protective, anti-inflammatory and anti-plasmodial effects. In addition to providing a summary of the structure-activity profiles of sucrose esters, the various known mechanisms-of action of these compounds are also discussed. Furthermore, since sucrose esters are well-known surfactants, the potential to advantageously apply their industrially desirable physical characteristics in combination with their biological properties is considered. Recent advances in synthetic chemistry that have facilitated the deployment of biologically active sucrose esters as food additives are also described.

Chemical Constituents from the Leaves of Ligustrum robustum and Their Bioactivities.

The leaves of Ligustrum robustum have been consumed as Ku-Ding-Cha for clearing heat and removing toxins, and they have been used as a folk medicine for curing hypertension, diabetes, and obesity in China. The phytochemical research on the leaves of L. robustum led to the isolation and identification of two new hexenol glycosides, two new butenol glycosides, and five new sugar esters, named ligurobustosides X (1a), X1 (1b), Y (2a), and Y1 (2b) and ligurobustates A (3a), B (3b), C (4b), D (5a), and E (5b), along with seven known compounds (4a and 6-10). Compounds 1-10 were tested for their inhibitory effects on fatty acid synthase (FAS), α-glucosidase, and α-amylase, as well as their antioxidant activities. Compound 2 showed strong FAS inhibitory activity (IC50 4.10 ± 0.12 µM) close to that of the positive control orlistat (IC50 4.46 ± 0.13 µM); compounds 7 and 9 revealed moderate α-glucosidase inhibitory activities; compounds 1-10 showed moderate α-amylase inhibitory activities; and compounds 1 and 10 displayed stronger 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) ammonium salt (ABTS) radical scavenging effects (IC50 3.41 ± 0.08~5.65 ± 0.19 µM) than the positive control l-(+)-ascorbic acid (IC50 10.06 ± 0.19 µM). This study provides a theoretical foundation for the leaves of L. robustum as a functional tea to prevent diabetes and its complications.

One-pot lipase-catalyzed esterification of ε-caprolactone with methyl-d-glucopyranoside and its elongation with free 6-hydroxyhexanoate monomer units.

One-pot synthesis of sugar-functionalized oligomeric caprolactone was carried out by lipase-catalyzed esterification of ε-caprolactone (ECL) with methyl-d-glucopyranoside (MGP) followed by the elongation of functionalized oligomer chain. Functionalization was performed in a custom-fabricated glass reactor equipped with Rushton turbine impeller and controlled temperature at 60 °C using tert-butanol as reaction medium. The overall reaction steps include MGP esterification of ECL monomer and its subsequent elongation by free 6-hydroxyhexanoate monomer units. A ping-pong bi-bi mechanism without ternary complex was proposed for esterification of ECL and MGP with apparent values of kinetic constant, namely maximal velocity (Vmax ), Michaelis constant for MGP (KmMGP ), and Michaelis constant for ECL (KmECL ) at 3.848 × 10-3  M H-1 , 8.189 × 10-2  M, and 6.050 M, respectively. Chain propagation step of MGP-functionalized ECL oligomer exhibits the properties of living polymerization mechanism. Linear relationship between conversion (%) and number average molecular weight, Mn (g mol-1 ), of functionalized oligomer was observed. Synthesized functionalized oligomer showed narrow range of molecular weight from 1,400 to 1,600 g mol-1 with more than 90% conversion achieved. Structural analysis confirmed the presence of covalent bond between the hydroxyl group in MGP with carboxyl end group of ECL oligomer.

Lipase-Catalyzed Synthesis of Sugar Esters in Honey and Agave Syrup.

Honey and agave syrup are high quality natural products and consist of more than 80% sugars. They are used as sweeteners, and are ingredients of cosmetics or medical ointments. Furthermore, both have low water content, are often liquid at room temperature and resemble some known sugar-based deep eutectic solvents (DES). Since it has been shown that it is possible to synthesize sugar esters in these DESs, in the current work honey or, as vegan alternative, agave syrup are used simultaneously as solvent and substrate for the enzymatic sugar ester production. For this purpose, important characteristics of the herein used honey and agave syrup were determined and compared with other available types. Subsequently, an enzymatic transesterification of four fatty acid vinyl esters was accomplished in ordinary honey and agave syrup. Notwithstanding of the high water content for transesterification reactions of the solvent, the successful sugar ester formation was proved by thin-layer chromatography (TLC) and compared to a sugar ester which was synthesized in a conventional DES. For a clear verification of the sugar esters, mass determinations by ESI-Q-ToF experiments and a NMR analysis were done. These environmentally friendly produced sugar esters have the potential to be used in cosmetics or pharmaceuticals, or to enhance their effectiveness.

Lactose esters: synthesis and biotechnological applications.

Biodegradable nonionic sugar esters-based surfactants have been gaining more and more attention in recent years due to their chemical plasticity that enables the various applications of these molecules. In this review, various synthesis methods and biotechnological implications of lactose esters (LEs) uses are considered. Several chemical and enzymatic approaches are described for the synthesis of LEs, together with their applications, i.e. function in detergents formulation and as additives that not only stabilize food products but also protect food from undesired microbial contamination. Further, this article discusses medical applications of LEs in cancer treatment, especially their uses as biosensors, halogenated anticancer drugs, and photosensitizing agents for photodynamic therapy of cancer and photodynamic inactivation of microorganisms.

Naturally Occurring Cinnamic Acid Sugar Ester Derivatives.

Cinnamic acid sugar ester derivatives (CASEDs) are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic of great interest over the past several decades. In particular the compound 3',6-disinapoylsucrose, the index component of Yuanzhi (a well-known Traditional Chinese Medicine or TCM), presents antidepressant effects at a molecular level, and has become a hotspot of research on new lead drug compounds. Several other similar cinnamic acid sugar ester derivatives are reported in traditional medicine as compounds to calm the nerves and display anti-depression and neuroprotective activity. Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae. This overview discusses the isolation of cinnamic acid sugar ester derivatives from plants, together with a systematic discussion of their distribution, chemical structures and properties and pharmacological activities, with the hope of providing references for natural product researchers and draw attention to these interesting compounds.

Antibacterial Effect of Fructose Laurate Synthesized by Candida antarctica B Lipase-Mediated Transesterification.

Sugar esters are valuable compounds composed of various sugars and fatty acids that can be used as antibacterial agents and emulsifiers in toothpaste and canned foods. For example, fructose fatty acid esters suppress growth of Streptococcus mutans, a typical pathogenic bacterium causing dental caries. In this study, fructose laurate ester was chosen as a target material and was synthesized by a transesterification reaction using Candida antarctica lipase B. We performed a solvent screening experiment and found that a t-butanol/dimethyl sulfoxide mixture was the best solvent to dissolve fructose and methyl laurate. Fructose laurate was synthesized by transesterification of fructose (100 mM) with methyl laurate (30 mM) in t-butanol containing 20% dimethyl sulfoxide. The conversion yield was about 90%, which was calculated based on the quantity of methyl laurate using high-performance liquid chromatography. Fructose monolaurate (Mr 361) was detected in the reaction mixture by high-resolution mass spectrometry. The inhibitory effect of fructose laurate on growth of oral or food spoilage microorganisms, including S. mutans, Bacillus coagulans, and Geobacillus stearothermophilus, was evaluated.

Efficient mono-acylation of fructose by lipase-catalyzed esterification in ionic liquid co-solvents.

Fructose monoesters are eco-friendly nonionic surfactants in various applications. Selective preparation of mono-acylated fructose is challenging due to the multiple hydroxyl sites available for acylation both chemically and enzymatically. Ionic liquids (ILs) have profound impacts not only on the reaction media but also on the catalytic properties of enzymes in the acylation process. In this study, utilizing an IL co-solvent system, selective synthesis of mono-acylated fructose with lauric acid catalyzed by immobilized Candida antarctica lipase B (CALB) was investigated. The imidazolium-based ILs selected as co-solvents with 2-methyl-2-butanol (2M2B) markedly improved the ratios of monolauroyl fructose in the presence of 60% [BMIM][TfO] (v/v) and 20% [BMIM][BF4] (v/v), in which the mono-acylated fructose was 85% and 78% respectively. Based on a Ping-Pong Bi-Bi model, a kinetic equation was fitted, by which the kinetic parameters revealed that the affinity between fructose and acyl-enzyme intermediate was enhanced. The inhibition effect of fructose on free enzyme was weakened in the presence of IL co-solvents. The conformation of CALB binding substrates also changed in the co-solvent system as demonstrated by Fourier transform infrared spectra. These results demonstrated that the variation of CALB kinetic characteristics was a crucial factor for the selectivity of mono-acylation in ILs/2M2B co-solvents.

Esterification degree of fructose laurate exerted by Candida antarctica lipase B in organic solvents.

Sugar esters of fatty acids have many applications as biocompatible and biodegradable emulsifiers, which are determined by their degrees of esterification (DE). Direct esterification of fructose with lauric acid in organic media used commercial immobilized Candida antarctica lipase B (CALB) was investigated for DE. Significant difference of DE was observed between 2-methyl-2-butanol (2M2B) and methyl ethyl ketone (MEK), as di-ester/mono-ester molar ratio of 1.05:1 in 2M2B and 2.79:1 in MEK. Fourier transform infrared (FTIR) spectra showed that the secondary structure of the enzyme binding mono-ester presented distinct difference in 2M2B and MEK. Contents of ß-turn and antiparallel ß-sheet of CALB in 2M2B were 26.9% and 16.2%, respectively, but 19.1% and 13.2% in MEK. To understand the relationship between the conformational changes and differences of DE, mono-ester and fatty acid were directly employed for synthesis of di-ester. The maximum initial velocity of di-ester synthesis in MEK was 0.59 mmolg(enzyme)(-1)h(-1), which was 2.19-fold as greater as that in 2M2B, indicating that CALB conformation in MEK was preferred for the synthesis of di-ester. These results demonstrated that the conformation of CALB binding mono-ester affected by organic solvents essentially determined DE.

Characterization of enzymatically prepared sugar medium-chain fatty acid monoesters.

BACKGROUND: Sugar medium-chain fatty acid esters are a new type of biodegradable, non-toxic, non-irritant and non-ionic surfactant with proven antimicrobial activity. Various sugar medium-chain fatty monoesters were prepared enzymatically using Lipozyme TLIM in organic solvent. Properties such as surface tension, antimicrobial activity, and ability to foam, emulsify and stabilize emulsions at room temperature were evaluated to conduct systematic studies on the structure-function relationships of these compounds. RESULTS: Results showed that all monoesters displayed good surface activity properties. In particular, sucrose monolaurate was the most excellent surfactant among 12 monoesters. Sugar monoesters containing C8 to C12 alkyl chains showed a broad spectrum of increasing antimicrobial activity. All tested monoesters were more effective against Staphylococcus aureus (Gram-positive bacterium) than Escherichia coli O157:H7 (Gram-negative bacterium). Methyl α-d-glycoside monoesters were the most effective, whereas raffinose monoesters possessed poor antimicrobial activity. CONCLUSIONS: Generally, the length of fatty acid chain (hydrophobic group) and sugar groups (hydrophilic group) for sugar medium-chain fatty acid monoesters both affected the surface properties and antimicrobial activities.

Sugar ester surfactants: enzymatic synthesis and applications in food industry.

Sugar esters are non-ionic surfactants that can be synthesized in a single enzymatic reaction step using lipases. The stability and efficiency of lipases under unusual conditions and using non-conventional media can be significantly improved through immobilization and protein engineering. Also, the development of de novo enzymes has seen a significant increase lately under the scope of the new field of synthetic biology. Depending on the esterification degree and the nature of fatty acid and/or sugar, a range of sugar esters can be synthesized. Due to their surface activity and emulsifying capacity, sugar esters are promising for applications in food industry.