[Quality control of Tianwang Buxin Pills based on UPLC fingerprint and multi-component quantification].

Tianwang Buxin Pills have demonstrated therapeutic effects in clinical practice, whereas there is a serious lack of comprehensive quality control to ensure the safety and effectiveness of clinical medication. In this study, ultra-performance liquid chromatography(UPLC) was employed to establish the fingerprint and the method for simultaneously determining the content of seven components of Tianwang Buxin Pills. Furthermore, chemometrics was employed to identify the key factors for the stable quality, which provided a reference for the comprehensive quality control and evaluation of this preparation. There were 25 common peaks in the UPLC fingerprints of 15 batches of Tianwang Buxin Pills, from which thirteen compounds were identified. A quantitation method was established for seven pharmacological components(α-linolenic acid, salvianolic acid B, glycyrrhetinic acid, schisandrin A, ß-asarone, 3,6'-disinapoylsucrose, and ligustilide). The principal component analysis(PCA) and partial least square discriminate analysis(PLS-DA) were performed to determine the key pharmacological components for controlling the quality stability of Tianwang Buxin Pills, which included 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone. The established fingerprint and multi-component content determination method have strong specificity, stability, and reliability. In addition, 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone are the key pharmacological components that ensure the quality stability between batches and can be used to comprehensively control the quality of Tianwang Buxin Pills. The findings provide a scientific basis for the quality evaluation and standard establishment of Tianwang Buxin Pills.

Sucralose (C12H19Cl3O8) impact on microbial activity in estuarine and freshwater marsh soils.

As the general population's diet has shifted to reflect current weight-loss trends, there has been an increase in zero-calorie artificial sweetener usage. Sucralose (C12H19Cl3O8), commonly known as Splenda® in the USA, is a primary example of these sweeteners. In recent years, sucralose has been identified as an environmental contaminant that cannot easily be broken down via bacterial decomposition. This study focuses on the impact of sucralose presence on microbial communities in brackish and freshwater systems. Microbial respiration and fluorescence were measured as indicators of microbial activity in sucralose-dosed samples taken from both freshwater and estuarine marsh environments. Results showed a significant difference between microbial concentration and respiration when dosed with varying levels of sucralose. Diatom respiration implied a negative correlation of community abundance with sucralose concentration. The freshwater cyanobacterial respiration increased in the presence of sucralose, implying a positive correlation of community abundance with sucralose concentration. This was in direct contrast to its brackish water counterpart. However, further investigation is necessary to confirm any potential utility of these communities in the breakdown of sucralose in the marsh environment.

Increased Intestinal Permeability and Decreased Resiliency of the Intestinal Barrier in Alcoholic Liver Disease.

INTRODUCTION: Only 20%-30% of individuals with alcohol use disorder (AUD) develop alcoholic liver disease (ALD). While the development of gut-derived endotoxemia is understood to be a required cofactor, increased intestinal permeability in ALD is not completely understood. METHODS: We recruited 178 subjects-58 healthy controls (HCs), 32 with ALD, 53 with AUD but no liver disease (ALC), and 35 with metabolic dysfunction-associated steatotic liver disease (MASLD). Intestinal permeability was assessed by a sugar cocktail as a percentage of oral dose. The permeability test was repeated after an aspirin challenge in a subset. RESULTS: Five-hour urinary lactulose/mannitol ratio (primarily representing small intestinal permeability) was not statistically different in HC, ALC, ALD, and MASLD groups ( P = 0.40). Twenty-four-hour urinary sucralose (representing whole gut permeability) was increased in ALD ( F = 5.3, P < 0.01) and distinguished ALD from ALC; 24-hour sucralose/lactulose ratio (primarily representing colon permeability) separated the ALD group ( F = 10.2, P < 0.01) from the MASLD group. After aspirin challenge, intestinal permeability increased in all groups and ALD had the largest increase. DISCUSSION: In a group of patients, we confirmed that (i) the ALD group has increased intestinal permeability compared with the HC, ALC, or MASLD group. In addition, because small bowel permeability (lactulose/mannitol ratio) is normal, the disruption of intestinal barrier seems to be primarily in the large intestine; (ii) decreased resiliency of intestinal barrier to injurious agents (such as NSAID) might be the mechanism for gut leak in subset of AUD who develop ALD.

Chronic sucralose consumption inhibits farnesoid X receptor signaling and perturbs lipid and cholesterol homeostasis in the mouse livers, potentially by altering gut microbiota functions.

Sucralose has raised concerns regarding its safety and recent studies have demonstrated that sucralose consumption can disrupt the normal gut microbiome and alter metabolic profiles in mice. However, the extent to which this perturbation affects the functional interaction between the microbiota and the host, as well as its potential impact on host health, remains largely unexplored. Here, we aimed to investigate whether chronic sucralose consumption, at levels within the Acceptable Daily Intake (ADI), could disturb key gut microbial functions and lead to adverse health effects in mice. Following six-month sucralose consumption, several bacterial genera associated with bile acid metabolism were decreased, including Lactobacillus and Ruminococcus. Consequently, the richness of secondary bile acid biosynthetic pathway and bacterial bile salt hydrolase gene were decreased in the sucralose-treated gut microbiome. Compared to controls, sucralose-consuming mice exhibited significantly lower ratios of free bile acids and taurine-conjugated bile acids in their livers. Additionally, several farnesoid X receptor (FXR) agonists were decreased in sucralose-treated mice. This reduction in hepatic FXR activation was associated with altered expression of down-stream genes, in the liver. Moreover, the expression of key lipogenic genes was up-regulated in the livers of sucralose-treated mice. Changes in hepatic lipid profiles were also observed, characterized by lower ceramide levels, a decreased PC/PE ratio, and a mildly increase in lipid accumulation. Additionally, sucralose-consumed mice exhibited higher hepatic cholesterol level compared to control mice, with up-regulation of cholesterol efflux genes and down-regulation of genes associated with reverse cholesterol transport. In conclusion, chronic sucralose consumption disrupts FXR signaling activation and perturbs hepatic lipid and cholesterol homeostasis, potentially by diminishing the bile acid metabolic capacity of the gut microbiome. These findings shed light on the complex interplay between sucralose, the gut microbiota, and host metabolism, raising important questions about the safety of its long-term consumption.

Sucralose regulates postprandial blood glucose in mice through intestinal sweet taste receptors Tas1r2/Tas1r3.

BACKGROUND: Non-nutritive sweeteners (such as sucralose) bind to sweet receptors Tas1r2/Tas1r3 on intestinal endocrine L cells after diets to upregulate blood glucose. However, the mechanism by which sucralose regulates postprandial blood glucose (PBG) has not been clarified to date. We hypothesized that the gut sweet taste receptor was one of the targets for sucralose to regulate PBG. The aim of this study was to examine the effect of sucralose on PBG based on the gut sweet taste receptor signaling pathway and to explore the mechanism. Therefore, we examined PBG, genes, and proteins associated with the gut sweet receptor pathway in sucralose-exposed mice. RESULTS: The results showed that after 12 weeks of sucralose exposure the PBG of mice increased significantly, and the expression of intestinal sweet taste receptors increased correspondingly. Within the concentration range of this experiment, a significant increase of PBG was observed in mice fed on sucralose with a concentration equal to or higher than 0.33 g L-1 . CONCLUSION: Long-term consumption of sucralose may increase body weight and the risk of elevated PBG, resulting in overexpression of sweetness receptors and glucose transporters. The mechanism of these effects might be the result of non-nutritive sweeteners binding to sweetness receptors Tas1r2/Tas1r3 in gut endocrine cells and upregulating Slc5a1 and Slc2a2. But we cannot rule out that the rise in PBG is the result of a combination of sweet receptors and gut microbes. Therefore, the effect of gut microbes on PBG needs to be studied further. © 2023 Society of Chemical Industry.

Ice cream with sucralose, stevioside, and erythritol as sugar substitutes: Sensory profile and customer preference.

Sugar-free food has been gaining popularity because of low-calorie content. But sugar replacement by high-intensity sweeteners can negatively affect sensory. In this study, the effect of the addition of sucralose (Suc), stevioside (Ste), and erythritol (Ery) as sugar substitutes on the sensory profile and overall acceptance of ice cream were evaluated by penalty analysis (PA) based on the check-all-that apply (CATA) method, with those of the partial least squares (PLS) regression. Twelve sweetening agents of ice cream samples were presented to 106 consumers who answered on an overall liking question using the 15-point hedonic scale and a CATA question with 32 attributes that described the sensory characteristics of ice cream. The results showed that mixed sweeteners (60%Suc+20%Ste+20%Ery or 60%Suc+10%Ste+30%Ery) can present an advantageous performance when used separately, and making ice cream similar to that of sucrose (Sac) added. Adding Suc, Ste, and Ery to ice cream hardly felt bitterness, astringency, and chemical-like sensations of the sweetening agent. The significant difference between different sweeteners is the intensity and speed of sweetness. Developing combination of high-potency sweeteners that can make sweetness appear quickly could open up new ways to design sugar-free ice cream.

Oral toxicity of an artificial sweetener sucralose on the German cockroach (Blattodea: Ectobiidae) and its impact on water balance and gut microbiome.

Artificial or non-nutritive sweeteners are indigestible by most animals. Some sweeteners are orally toxic to insects and have received recent interest as potential safe insecticides due to their low mammalian toxicity. In this study, we investigated the oral toxicity of sucralose on insecticide-susceptible and resistant German cockroaches, Blattella germanica (L.). In a nonchoice test, we evaluated 5, 10, and 20% sucralose solutions. Depending on the cockroach strains, mean mortality ranged from 62.5 to 92.5%, 15 to 55%, and 2.5 to 27.5% for 20, 10, and 5% sucralose, respectively. Next, we measured the impact of a 20% sucralose treatment on water loss rates in the cockroach strains. All strains lost 23.0-30.29% of body water by 6 d. Dehydrated cockroaches were more prone to be killed by sucralose than nondehydrated ones. Lastly, we evaluated the effect of 20% sucralose treatment on gut bacterial composition and found the diversity of gut bacteria in treated cockroaches was significantly reduced after 3 days, implicating a rapid change in the alimentary environment.

The dietary sweetener sucralose is a negative modulator of T cell-mediated responses.

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2-5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.

Simultaneous determination of lactulose, sucrose, sucralose, and mannitol using high-performance liquid chromatography-refractive index to estimate intestinal permeability in patients with active ulcerative colitis.

OBJECTIVES: The intestinal permeability (IP) of sugars and their derivatives has been widely used to assess mucosal damage in gastrointestinal diseases. Ulcerative colitis (UC) is a recurring and relapsing disease that causes inflammation of the gut. IP of sugars can be evaluated and correlated with the flare of UC. MATERIALS AND METHODS: A prospective study was conducted on 91 patients with active UC at the tertiary care center in North India. Mayo grading system assessed disease activity, and IP was assessed by measuring sucrose, lactulose, mannitol, and sucralose in urine samples from UC patients. A high-performance liquid chromatography (HPLC) method to detect all of these sugars simultaneously using a refractive index detector was developed and further validated in patients with UC. RESULTS: The analytical recovery rate of the tested sugars ranged from 95% to 146% in the urine matrix. The limit of detection and limit of quantification were 78.838 mg/L and 262.79 mg/L for sucrose, 84.994 mg/L and 283.31 mg/L for lactulose, 74.789 mg/L and 249.30 mg/L for mannitol, and 50.908 mg/L and 169.69 mg/L for sucralose. CONCLUSION: The standardized HPLC method is sensitive and suitable for the simultaneous detection and determination of different sugar moieties in the urine sample. Patients with UC can be evaluated indirectly for the flare by estimating the recovery rate of sugars through gut permeability. The procedure is noninvasive and thus improves the quality of life of chronically ill patients.

Improvement of methods for analysing sucrose acetate isobutyrate (SAIB) in soft drinks using GC-FID and evaluating antioxidant effects in the SAIB emulsion system.

Sucrose acetate isobutyrate SAIB (E444) is a mixture produced by the esterification of sucrose with acetic anhydride and isobutyric anhydride. It is a food additive that is used as an emulsifier in soft drinks. It is difficult to analyse SAIB quantitatively because there are 256 synthesisable structures in the mixture. This study developed an analytical method for SAIB using gas chromatography-flame ionization detection (GC-FID). The pre-treatment of SAIB in soft drinks was performed using a liquid-liquid extraction method, which demonstrated a recovery rate of 107.8 ± 7.2%. In the GC-FID analysis of SAIB, numerous peaks were observed in the chromatogram, and the content of SAIB was calculated as the sum of these peak areas. A series of analytical methods were validated according to International Conference for Harmonization (ICH) guidelines. Accordingly, the applicability of the developed analytical method was confirmed for both domestic and imported soft drinks distributed in Korea. Additionally, in the linoleic acid emulsion, SAIB exhibited better lipid oxidation stability than the natural antioxidant α-tocopherol and had similar efficacy to the synthetic antioxidant butylated hydroxytoluene (BHT). Although SAIB has excellent lipid oxidation stability, it must be used within legal standards according to consumer demand to reduce the use of synthetic materials in processed foods. The validated GC-FID analytical method will enable subsequent monitoring of the distributed products.

Sucralose hydrogels: Peering into the reactivity of sucralose versus sucrose under lipase catalyzed trans-esterification.

Sucralose differs from sucrose only by virtue of having three Cl groups instead of OH groups. Its intriguing features include being noncaloric, noncariogenic, ∼600 times sweeter than sucrose, stable at high temperatures/acidic pH's, and void of disagreeable aftertastes. These properties are attractive as food additive, one of which is as hydrogel obtainable via the technique of molecular gelation using a sucralose-derived low-molecular weight gelator (LMWG). Such hydrogels are highly responsive to external stimuli like temperature, because the LMWGs self-assemble via non-covalent interactions and could thus be utilized in applications like control-release. We found that sucralose to be unreactive under lipase biocatalysis, unlike sucrose. Hence, the aim of this work was (i) to use computational simulations to further understand sucralose's lack of enzymatic reactivity and (ii) to synthesize the sucralose-based amphiphiles using conventional chemical synthesis and systematically study their tendency towards hydrogelation. Sucrose and sucralose were docked with a high-resolution atomic structure of lipase B from Candida antarctica, modeling the esterification transition state with an active site serine. In extended molecular dynamics simulations, sucrose remained in the active site due to multiple sugar-protein hydrogen bonds. The oxygen-to-chlorine substitutions in sucralose disrupted this hydrogen bonding network. Consistent with observed lack of enzymatic conversion, in multiple simulations, sucralose would rapidly dissociate from the active site. The sucralose-based LMWGs were subsequently synthesized using base-catalyzed conventional chemical synthesis. Three of the sucralose-based amphiphiles (SL-5, SL-6 and SL-7) proved to be successful hydrogelators. The gelators also showed the ability to gel selected beverages. The LMWGs gelled quantities of water and beverage up to 71 and 55 times their weight, respectively, and remain thermally stable up to 144 °C.

Sucralose as an oxidative-attenuation tracer for characterizing the application of in situ chemical oxidation for the treatment of 1,4-dioxane.

In situ chemical oxidation (ISCO) has become a widely used soil and groundwater remediation method. Oxidative-attenuation tracers can be used to provide real-time, explicit delineation of contaminant mass-transfer and transformation behavior during an ISCO remediation project. The objective of this study was to evaluate the potential of employing sucralose, a widely used artificial sweetener, as an oxidative-attenuation tracer to characterize the remediation efficiency of 1,4-dioxane (dioxane) by persulfate-based ISCO. Batch and miscible-displacement experiments were conducted to examine the degradation rate and transport behavior of sucralose compared to that of dioxane. Comparable magnitudes and rates of degradation were observed for sucralose and dioxane in batch-reactor experiments with soil and persulfate. The breakthrough curves of sucralose and dioxane transport in a soil-packed column were coincident. The retardation factors were 1.1 for both compounds, indicating limited sorption for both sucralose and dioxane by the soil. Limited degradation was observed in the miscible-displacement experiments, consistent with the short residence time compared to the half-lives of sucralose and dioxane. Persulfate transport and decomposition behavior in the soil-packed columns was similar in the presence of sucralose or dioxane. A simulated tracer test was conducted to illustrate the application of sucralose as an oxidative-attenuation tracer at the pilot scale. These results demonstrate the potential of sucralose as an oxidative-attenuation tracer to support the robust design of ISCO applications for dioxane. The oxidative-attenuation tracer test method is anticipated to be an effective approach for characterizing mass-removal behavior of other emerging contaminants with appropriate selection of tracer.

A Potential Role of Keratinocyte-Derived Bilirubin in Human Skin Yellowness and Its Amelioration by Sucrose Laurate/Dilaurate.

Sallow and/or dull skin appearance is greatly attributable to the yellow components of skin tone. Bilirubin is a yellow chromophore known to be made in the liver and/or spleen and is transported throughout the body via the blood stream. Recent publications suggest bilirubin may be synthesized in other cells/organs, including the skin. We found human keratinocytes express the transcripts involved in bilirubin biosynthesis. In parallel, we also found human keratinocytes could indeed synthesize bilirubin in monolayer keratinocytes and in a 3D human skin-equivalent model. The synthesized amount was substantial enough to contribute to skin yellowness. In addition, oxidative stress enhanced bilirubin production. Using UnaG, a protein that forms a fluorescent species upon binding to bilirubin, we also visualized the intracellular expression of bilirubin in keratinocytes. Finally, we screened a compound library and discovered that the sucrose laurate/dilaurate (SDL) combination significantly reduced bilirubin levels, as well as bilirubin-mediated yellowness. In conclusion, bilirubin is indeed synthesized in epidermal keratinocytes and can be upregulated by oxidative stress, which could contribute to chronic or transient yellow skin tone appearance. Application of SDL diminishes bilirubin generation and may be a potential solution to mitigate yellowish and/or dull skin appearance.

Potential Effects of Sucralose and Saccharin on Gut Microbiota: A Review.

Artificial sweeteners are additives widely used in our diet. Although there is no consensus, current evidence indicates that sucralose and saccharin could influence the gut microbiota. The aim of this study was to analyze the existing scientific evidence on the effects of saccharin and sucralose consumption on gut microbiota in humans. Different databases were used with the following search terms: sweeteners, non-caloric-sweeteners, sucralose, splenda, saccharin, sugartwin, sweet'n low, microbiota, gut microbiota, humans, animal model, mice, rats, and/or in vitro studies. In vitro and animal model studies indicate a dose-dependent relationship between the intake of both sweeteners and gut microbiota affecting both diversity and composition. In humans, long-term study suggests the existence of a positive correlation between sweetener consumption and some bacterial groups; however, most short-term interventions with saccharin and sucralose, in amounts below the ADI, found no significant effect on those groups, but there seems to be a different basal microbiota-dependent response of metabolic markers. Although studies in vitro and in animal models seem to relate saccharin and sucralose consumption to changes in the gut microbiota, more long-term studies are needed in humans considering the basal microbiota of participants and their dietary and lifestyle habits in all population groups. Toxicological and basal gut microbiota effects must be included as relevant factors to evaluate food safety and nutritional consequences of non-calorie sweeteners. In humans, doses, duration of interventions, and number of subjects included in the studies are key factors to interpret the results.

Acute exposure to environmentally relevant concentrations of sucralose disrupts embryonic development and leads to an oxidative stress response in Danio rerio.

Sucralose (SUC) is the most consumed artificial sweetener worldwide, not metabolized by the human body, and barely eliminated from water in wastewater treatment plants. Although different studies have reported high concentrations of this sweetener in aquatic environments, limited to no information is known about the toxic effects this drug may produce over water organisms. Moreover, most of the current studies have used non-environmentally relevant concentrations of SUC for these effects. Herein, we aimed to evaluate the harmful effects that environmentally relevant concentrations of SUC may induce in the early life stages of Danio rerio. According to our results, SUC altered the embryonic development of D. rerio, producing several malformations that led to their death. The major malformations were scoliosis, pericardial edema, yolk deformation, and tail malformation. However, embryos also got craniofacial malformations, eye absence, fin absence, dwarfism, delay of the hatching process, and hypopigmentation. SUC also generated an oxidative stress response in the embryos characterized by an increase in the levels of lipid peroxidation, hydroperoxides, and carbonyl proteins. To overcome this oxidative stress response, we observed a significant increase in the levels of antioxidant enzymes superoxide dismutase and catalase. Moreover, a significant boost in the expression of antioxidant defense-related genes, Nuclear respiratory factor 1a (Nrf1a) and Nuclear respiratory factor 2a (Nrf2a), was also observed at all concentrations. Concerning apoptosis-related genes, we observed the expression of Caspase 3 (CASP3) and Caspase 9 (CASP9) was increased in a concentration-dependent manner. Overall, we conclude environmentally relevant concentrations of SUC are harmful to the early life stages of fish as they produce malformations, oxidative stress, and increased gene expression of apoptosis-related genes on embryos.

Antibacterial mechanism of sucrose laurate against Bacillus cereus by attacking multiple targets and its application in milk beverage.

Sucrose laurate (SL) is a promising dual-functional additive due to its emulsification and antibacterial activity. However, the knowledge on the antibacterial action of SL against Bacillus cereus was lacking, and thus it was investigated from multiple targets. The antibacterial results demonstrated that the minimum inhibitory concentration of SL was 0.3125 mg/mL, and the time-killing curve confirmed the strong antibacterial activity of SL. The alkaline phosphatase assay suggested that SL disrupted the cell wall integrity. The flow cytometry and fluorescence spectroscopy analysis indicated that SL damaged the integrity of cell membrane and dissipated the transmembrane potential, resulting in the leakage of intracellular materials, which were further supported by scanning electron microscopy and transmission electron microscopy. iTRAQ-based proteomic analysis indicated that SL down-regulated cell wall-associated hydrolase, inhibited the synthesis of fatty acids, influenced nucleic acid synthesis, disturbed amino acid metabolism, and blocked HMP pathway and TCA cycle. Finally, the promising application of SL was evidenced in milk beverage. This investigation could provide scientific basis for the practical application of SL as a dual-functional food additive.

Economic Evaluation of Sucrose Octasulfate Dressing for Treatment of Diabetic Foot Ulcers in Patients with Type 2 Diabetes.

OBJECTIVES: Patients with noninfected neuroischemic diabetic foot ulcers (DFUs) treated with sucrose octasulfate (SOS) dressing have been shown to have improved healing compared with patients wearing a similar type of dressing without SOS. In this study, we aimed to estimate the cost-effectiveness of SOS dressing compared with conventional dressings from a Canadian public payer's perspective. METHODS: We built a Markov model in a hypothetical cohort of 1,000 inpatients with type 2 diabetes with DFUs. The time horizon was 5 years, and the cycle length was 3 months. We incorporated effectiveness data from the Explorer trial and cohort studies, cost data (2020 Canadian dollars) from published Canadian studies and administrative databases, and utility parameters from the Alberta's Caring for Diabetes cohort. We used probabilistic analysis to calculate the incremental cost-effectiveness ratio of SOS dressing compared with conventional dressings. RESULTS: In the comparison with conventional dressings, use of SOS dressing resulted in an expected increase of 0.16 quality-adjusted life-year (QALY) and an expected $5,878 decrease in health-care costs over 5 years. Adding SOS dressing resulted in a cost savings of $37,061 for every QALY gained. The probability that adding SOS dressing is cost-saving and cost-effective compared with conventional dressings was 89% and 86%, respectively, at a $50,000/QALY willingness-to-pay threshold. CONCLUSIONS: SOS dressing accelerates ulcer healing and helps reduce the spending induced by persistent ulcer management and amputation. Therefore, SOS dressing is likely to be cost-effective and cost-saving, which is consistent with previous health technology assessments in other health-care systems.

Sucrose Acetate Isobutyrate (SAIB) as a Delivery Vehicle for Estradiol and Sulpiride: Evaluation of Endocrine Responses in Geldings and Ovarian Response in Seasonally Anovulatory Mares.

Sulpiride in vegetable shortening (VS) stimulates prolactin in horses for up to 10 days. Although effective, a pharmaceutical grade vehicle is needed for clinical application of sulpiride in horses. Sucrose acetate isobutyrate (SAIB), a hydrophobic polymer, may be an alternative to VS. Four in vivo experiments assessed the efficacy of SAIB for delivery of sulpiride, estradiol cypionate (ECP), and estradiol benzoate (EB). The first three studies utilized geldings to compare prolactin and luteinizing hormone (LH) concentrations between sulpiride delivered in VS and SAIB, and ECP or EB delivered in SAIB. Sulpiride stimulated (P < .01) prolactin similarly between vehicles. Geldings pretreated with EB had higher (P < .05) prolactin responses to sulpiride compared to ECP-treated geldings on days 5, 6 and 9. Both estradiol-sulpiride treatments stimulated LH with no differences between ECP and EB. Experiment 3 compared a simultaneous injection of EB-sulpiride to a non-simultaneous injection (one day apart) of EB-sulpiride. Prolactin was stimulated (P < .05) in both treatment groups, but the response lasted 2 days longer in geldings treated a day apart. Plasma LH increased (P < .01) in both groups equally for 10 days. Experiment 4 applied simultaneous and non-simultaneous EB-sulpiride treatments to seasonally anovulatory mares to induce ovarian activity. Prolactin and LH were stimulated similarly between treatments; however, non-simultaneously treated mares tended (P = .07) to have an ovarian response earlier. In conclusion, SAIB was a suitable vehicle for administration of estradiol and sulpiride and could be an alternative to VS for sustained-release drug delivery.

The combination of sucrose dilaurate and sucrose laurate suppresses HMGB1: an enhancer of melanocyte dendricity and melanosome transfer to keratinocytes.

BACKGROUND: Hyperpigmented spots are common issues in all ethnicities, involving multiple intrinsic and extrinsic factors such as UVB exposure, hormone balance, inflammatory status and ageing. OBJECTIVES: To determine (i) melanocyte dendricity in multiple facial spot types, (ii) impact of High Mobility Group Box 1 (HMGB1), and the combination of sucrose dilaurate and sucrose laurate (SDL) on melanogenesis and melanocyte dendricity, and (iii) SDL effect on facial spots in a human use test. METHODS: Facial spot and adjacent non-spot skin biopsies were collected from Chinese women (age 20-70). Histological assessment of melanocyte dendricity was performed for 3 spot types (solar lentigo, melasma and postinflammatory hyperpigmentation) by immunofluorescent staining for c-kit/MITF. Keratinocyte, melanocyte and melanocyte-keratinocyte co-culture models were used to assess HMGB1 release by UVB radiation, the effects of HMGB1 and SDL on melanin production, melanocyte dendricity and melanosome transfer. The effect of an SDL-containing moisturizer on appearance of facial hyperpigmented spots was assessed against a vehicle control in an 8-week human use test. RESULTS: Melanocytes in spot areas are more dendritic than melanocytes in adjacent non-spot skin across three investigated spot types. In cell culture models, a moderate UVB-radiation exposure caused release of HMGB1 from keratinocytes. HMGB1 did not alter melanin production in melanocytes, but enhanced melanocyte dendricity and melanosome transfer. SDL reduced HMGB1 release from keratinocytes, inhibited melanin production, reversibly suppressed melanocyte dendricity and reduced melanosome transfer. In the human use test, SDL-containing moisturizer reduced appearance of spots versus vehicle. CONCLUSION: Increased melanocyte dendricity was observed in multiple types of facial spots. Addition of HMGB1 protein increased melanocyte dendricity and melanosome transfer in cell cultures, implicating potential involvement in spot formation. SDL suppressed melanin production, melanocyte dendricity and melanosome transfer in vitro and reduced appearance of spots in the use test, suggesting SDL is an effective solution to address hyperpigmented spot concerns.

Development of Fully Redispersible Dried Nanocrystals by Using Sucrose Laurate as Stabilizer for Increasing Surface Area and Dissolution Rate of Poorly Water-Soluble Drugs.

There is much interest in converting poorly water-soluble drugs into nanocrystals as they provide extremely high surface area that increases dissolution rate and oral bioavailability. However, nanocrystals are prepared as aqueous suspensions, and once the suspensions are dried for development of solid dosage forms, the nanocrystals agglomerate as large particles to reduce the excess surface energy. For successful development of drug products, it is essential that any agglomeration is reversible, and the dried nanocrystals regain original particle sizes after redispersion in aqueous media. We have established that sucrose laurate serves as a superb stabilizer to ensure complete redispersion of dried nanocrystals in aqueous media with mild agitation. Nanocrystals (150-300 nm) of three neutral drugs (fenofibrate, danazol and probucol) were produced with sucrose laurate by media milling, and suspensions were dried by tray drying under vacuum, spray drying, and lyophilization. Dried solids and their tablets redispersed into original particle sizes spontaneously. Preliminary studies showed that sucrose laurate can also redisperse acidic and basic drugs, indicating its versatile application. Fatty acid ester of another disaccharide, lactose laurate, also performed like sucrose laurate. Thus, we have developed a method of retaining high dissolution rate and, by implication, high bioavailability of nanocrystals from solid formulations.