Sucrose Laurate Research Articles

Co-delivery of paclitaxel and anti-VEGF siRNA by tripeptide lipid nanoparticle to enhance the anti-tumor activity for lung cancer therapy

The combination of chemotherapeutic drug paclitaxel (PTX) and VEGF siRNA could inhibit cancer development with synergistic efficacy. However, efficient and safe delivery systems with high encapsulation efficiency of PTX and a long-time release of drugs are urgently needed. In this study, novel nanoparticles (PTX/siRNA/FALS) were constructed by using tripeptide lipid (L), sucrose laurate (S), and folate-PEG2000-DSPE (FA) to co-deliver PTX and siRNA. The cancer cell targeting nanoparticle carrier (PTX/siRNA/FALS) showed anticipated PTX encapsulation efficiency, siRNA retardation ability, improved cell uptake and sustained and controlled drug release. It led to significant anti-tumor activity in vitro and in vivo by efficient inhibition of VEGF expression and induction of cancer cell apoptosis. Importantly, the biocompatibility of the carriers and low dosage of PTX required for effective therapy greatly reduced the toxicity to mice. The targeting nanoparticles show potential as an effective co-delivery platform for RNAi and chemotherapy drugs, aiming to improve the efficacy of cancer therapy.

Hydrophobic H-bond pairing: A novel approach to improve membrane permeability.

The aim of the present study was to develop hydrophobic H-bond pairs (HHPs) of leuprolide (LEU) with non-ionic surfactants to improve its membrane permeability. LEU was lipidized via hydrophobic H-bond pairing (HHP) with the sucrose esters (SEs) sucrose laurate HLB 15 (SLA-15), sucrose palmitate HLB 16 (SPA-16), sucrose stearate HLB 11 (SST-11) and sucrose stearate HLB 15 (SST-15). HHPs were evaluated regarding precipitation efficiency in water, zeta potential, log Pn-octanol/water and dissociation behavior at various pH over time. Cytotoxic potential of HHPs of LEU with SST-11 was investigated on Caco-2 cells. Subsequently, ex vivo permeation studies were carried out across freshly excised Sprague-Dawley rat intestinal mucosa. At a molar ratio of LEU to SEs of 1:≥1 a precipitation efficiency of above 50% was achieved. Zeta potential of complexes was neither influenced by the type nor the amount of added surfactants. Log Pn-octanol/water of LEU was up to 250-fold increased due to HHP utilizing SST-11. Dissociation studies showed that HHPs of LEU with SST-11 dissociate up to 20% in gastrointestinal (GI) pH conditions within 4h. Moreover, HHPs of LEU with SST-11 exhibited no cytotoxicity. Ex vivo permeation studies revealed 2-fold improved membrane permeation of HHPs of LEU with SST-11 compared to free LEU. Findings of this study show that HHP can be considered as a promising strategy to improve membrane permeation.

Evaluation of Sucrose Laurate as an Intestinal Permeation Enhancer for Macromolecules: Ex Vivo and In Vivo Studies.

Oral delivery of macromolecules requires permeation enhancers (PEs) adaptable to formulation. Sucrose laurate (SL) (D1216), a food grade surfactant, was assessed in Caco-2 monolayers, isolated rat intestinal tissue mucosae, and rat intestinal instillations. Accordingly, 1 mM SL increased the apparent permeability coefficient (Papp) of [14C]-mannitol and reduced transepithelial electrical resistance (TEER) across monolayers. It altered expression of the tight junction protein, ZO-1, increased plasma membrane potential, and decreased mitochondrial membrane potential in Caco-2 cells. The concentrations that increased flux were of the same order as those that induced cytotoxicity. In rat colonic tissue mucosae, the same patterns emerged in respect to the concentration-dependent increases in paracellular marker fluxes and TEER reductions with 5 mM being the key concentration. While the histology revealed some perturbation, ion transport capacity was retained. In rat jejunal and colonic instillations, 50 and 100 mM SL co-administered with insulin induced blood glucose reductions and achieved relative bioavailability values of 2.4% and 8.9%, respectively, on a par with the gold standard PE, sodium caprate (C10). The histology of the intestinal loops revealed little damage. In conclusion, SL is a candidate PE with high potential for emulsion-based systems. The primary action is plasma membrane perturbation, leading to tight junction openings and a predominant paracellular flux.

Heat Treatment of Poloxamer-Stabilized Triglyceride Nanodispersions: Effects and Underlying Mechanism.

Lipid nanoemulsions are being investigated for the parenteral administration of poorly soluble drugs. A narrow particle size distribution in these formulations is a prerequisite for meaningful research and safe administration to patients. Autoclaving a poloxamer-stabilized trimyristin nanoemulsion resulted in moderate particle growth and a strong decrease in particle size distribution width ( Göke , K. ; Roese , E. ; Arnold , A. ; Kuntsche , J. ; Bunjes , H. Mol. Pharmaceutics 2016 , 13 , 3187 . ). In this work, the critical parameters for such a change upon autoclaving poloxamer 188-stabilized lipid nanodispersions were investigated to elucidate the underlying mechanism. Nanodispersions of triglycerides with esterified fatty acid chain lengths from C8 to C18 were treated at different temperatures and for varying durations. The influence of a decrease in poloxamer 188's cloud point was tested by adding potassium chloride to the dispersions prior to autoclaving. The influence of poloxamer 188 concentration and of the type of emulsifier was investigated. The change in particle size and particle size distribution width upon heat treatment was analyzed by dynamic or static light scattering or differential scanning calorimetry. A short esterified fatty acid chain length of the triglycerides, high temperatures, and the addition of potassium chloride were key factors for particle growth up to emulsion break up, whereas the cloud point of poloxamer 188 was irrelevant. Sodium dodecyl sulfate and sucrose laurate had negative effects on emulsion stability during autoclaving. It was concluded that the increase in particle size and the decrease in particle size distribution widths upon heat treatment resulted from heat-accelerated Ostwald ripening and not from a coalescence-based process.

Improvement of Dissolution Rate of Oxcarbazepine Using Surface‐modified Solid Dispersion with Vinylpyrrolidone‐Vinyl Acetate Copolymer and Sucrose Laurate

Improvement of Dissolution Rate of Oxcarbazepine Using Surface‐modified Solid Dispersion with Vinylpyrrolidone‐Vinyl Acetate Copolymer and Sucrose Laurate

Hydrophilic and lipophilic characteristics of non-fatty acid moieties: significant factors affecting antibacterial activity of lauric acid esters.

It has been proposed that the hydrophilic and/or lipophilic characteristics of fatty acid derivatives affect their antibacterial activities according to their ability to incorporate into the bacterial cell membrane. To verify this hypothesis, six kinds of lauric acid derivatives esterified with different non-fatty acid moieties were selected to confirm whether antibacterial activity from their precursor (i.e., lauric acid) is retained or lost. Three compounds, monolaurin, sucrose laurate, and erythorbyl laurate, exerted bacteriostatic and bactericidal effects against Gram-positive bacteria, while the others showed no inhibitory activity. Interestingly, the calculated log P (octanol-water partition coefficient) values of monolaurin, sucrose laurate, and erythorbyl laurate were -4.122, -0.686, and 3.670, respectively, relatively lower than those of the other compounds without antibacterial activity. Moreover, the hydrophilic-lipophilic balance values of the three compounds with antibacterial activity were higher than those of the other compounds, corresponding to the log P result.

Effects of surfactant-based permeation enhancers on mannitol permeability, histology, and electrogenic ion transport responses in excised rat colonic mucosae

Surfactant-based intestinal permeation enhancers (PEs) are constituents of several oral macromolecule formulations in clinical trials. This study examined the interaction of a test panel of surfactant-based PEs with isolated rat colonic mucosae mounted in Ussing chambers in an attempt to determine if increases in transepithelial permeability can be separated from induction of mucosal perturbation. The aim was to assess the effects of PEs on (i) apparent permeability coefficient (Papp) of [14C]-mannitol (ii) histology score and (iii) short-circuit current (ΔIsc) responses to a cholinomimetic (carbachol, CCh). Enhancement ratio increases for Papp values followed the order: C10 > C9 = C11:1 > a bile salt blend > sodium choleate > sucrose laurate > Labrasol® >C12E8 > C12 > Cremophor® A25 > C7 > sucrose stearate > Kolliphor® HS15 > Kolliphor® TPGS. Exposures that increased the Papp by ≥2-fold over 120 min were accompanied by histological damage in 94% of tissues, and by a decreased ΔIsc response to CCh in 83%. A degree of separation between the increased Papp of [14C]-mannitol and histological damage and diminution of the ΔIsc response to CCh was observed at selected concentrations of Labrasol®. Overall, this surfactant-based PE selection caused transcellular perturbation at similar concentrations to those that enhanced permeability.

Preparation of lipid nanoemulsions by premix membrane emulsification with disposable materials

The possibility to prepare nanoemulsions as drug carrier systems on small scale was investigated with disposable materials. For this purpose premix membrane emulsification (premix ME) as a preparation method for nanoemulsions with narrow particle size distributions on small scale was used. The basic principle of premix ME is that the droplets of a coarse pre-emulsion get disrupted by the extrusion through a porous membrane. In order to implement the common preparation setup for premix ME with disposable materials, the suitability of different syringe filters (made from polyethersulfone, cellulose acetate, cellulose ester and nylon) and different pharmaceutically relevant emulsifiers (phospholipids, polysorbate 80 and sucrose laurate) for the preparation of nanoemulsions was investigated. Already the preparation of the premix could be realized by emulsification with the help of two disposable syringes. As shown for a phospholipid-stabilized emulsion, the polyethersulfone filter was the most appropriate one and was used for the study with different emulsifiers. With this syringe filter, the median particle size of all investigated emulsions was below 500nm after 21 extrusion cycles through a 200nm filter and a subsequent extrusion cycle through a 100nm filter. Furthermore, the particle size distribution of the polysorbate 80- and sucrose laurate-stabilized emulsions prepared this way was very narrow (span value of 0.7).

Green Synthesis of Sucrose Laurate Under Different Ultrasonic Frequencies

In this study, the effects of ultrasonic parameters on the synthesis of sucrose laurate were investigated under four frequencies (20, 33, 53, and 80 kHz). Results indicated that low ultrasonic frequency increases sucrose monolaurate yield, whereas high ultrasonic frequency increases sucrose dilaurate yield. As the sound intensity increases from 0.55 to 1.04 W cm−2, the yield of sucrose laurate also increases, whereas the reaction time decreases. The yield of sucrose laurate decreased, and the reaction time prolonged with the decreasing pulse width. Both the initial production rate of sucrose monolaurate and the yield of sucrose dilaurate increased with the increasing temperature from 60 to 90 °C. However, further increase in the reaction temperature did not increase the yield of sucrose monolaurate but significantly reduced the reaction time. Sucrose laurate synthesized under ultrasonic frequency consisted of sucrose monolaurate, dilaurate, and polylaurate.

Solvent-Free Lipase-Catalyzed Synthesis of Technical-Grade Sugar Esters and Evaluation of Their Physicochemical and Bioactive Properties

Technical-grade oleic acid esters of sucrose and fructose were prepared using solvent-free biocatalysis at 65 °C, without any downstream purification applied, and their physicochemical and bioactivity-related properties were evaluated and compared to a commercially available sucrose laurate emulsifier. To increase the conversion of sucrose and fructose oleate, prepared previously using solvent-free lipase-catalyzed esterification catalyzed by Rhizomucor miehei lipase (81% and 83% ester, respectively), the enzymatic reaction conditions was continued using CaSO4 to control the reactor’s air headspace and a lipase (from Candida antarctica B) with a hydrophobic immobilization matrix to provide an ultralow water activity, and high-pressure homogenation, to form metastable suspensions of 2.0–3.3 micron sized saccharide particles in liquid-phase reaction media. These measures led to increased ester content of 89% and 96% for reactions involving sucrose and fructose, respectively. The monoester content among the esters decreased from 90% to <70% due to differences in regioselectivity between the lipases. The resultant technical-grade sucrose and fructose lowered the surface tension to <30 mN/m, and possessed excellent emulsification capability and stability over 36 h using hexadecane and dodecane as oils, comparable to that of sucrose laurate and Tween® 80). The technical-grade sugar esters, particularly fructose oleate, more effectively inhibited gram-positive foodborne pathogens (Lactobacillus plantarum, Pediococcus pentosaceus and Bacillus subtilis). Furthermore, all three sugar esters displayed antitumor activity, particularly the two sucrose esters. This study demonstrates the importance of controlling the biocatalysts’ water activity to achieve high conversion, the impact of a lipase’s regioselectivity in dictating product distribution, and the use of solvent-free biocatalysis to important biobased surfactants useful in foods, cosmetics, personal care products, and medicine.

Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance

To elaborate the decisive role of surfactants in promotion of aceclofenac’ skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester- over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81±5.97 and 60.86±3.67 vs. 27.00±5.09μg/cm2, and its maximum plasma concentrations 275.57±109.49 and 281.31±76.76 vs. 150.23±69.74ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery.

New Approach of Sucrose Myristate as a Promising Penetration Enhancer in Dermal Preparations

AbstractThe aim of this work was to compare the penetration enhancer effect of newly developed sucrose myristate with the generally used sucrose laurate. Hydrogel formulations containing sucrose esters (SEs) were prepared and the model drug was Ibuprofen (IBU), which has oral side effects, so applying it in a transdermal system could be useful. We evaluated the effect of SE hydrogel formulations on the skin by the noninvasive in vivo test and examined their concentration dependent influence on the penetration of IBU through a synthetic membrane (in vitro) by the Franz cell method. The results indicated that sucrose myristate incorporated into hydrogel moistures the skin well and lastingly and showed a better drug penetration enhancing effect at a much lower concentration compared to sucrose laurate. Our results revealed that sucrose myristate could be a promising and effective penetration enhancer in the pharmaceutical field.

Structural Analyses of Sucrose Laurate Regioisomers by Mass Spectrometry Techniques

GRAPHICAL ABSTRACT

Experimental Study of Foam Flow in Sand Columns: Surfactant Choice and Resistance Factor Measurement

Contamination of soil and groundwater with nonaqueous phase liquid represents a major environmental concern because of the negative effect on human health. Traditional soil flushing techniques have been proved ineffective in heterogeneous aquifers, since liquids for remediation flow preferentially through the most permeable layers and residual oil remains trapped in the low-permeability sediments. To improve the sweep efficiency, fluids with lower mobility than resident liquids can be injected, such as polymers or in situ generated foam. In addition, foam has the potential of selectively reducing mobility in higher-permeability layers compared to lower-permeability layers. The use of foams has not been popular because foam mobility is difficult to predict. In this paper, a series of 1D column experiments were conducted to investigate the variation of the resistance factor RF as a function of the permeability. Five types of sand and calibrated glass beads were used to obtain porous media of permeabilities ranging from 250 millidarcy to 100 Darcy. Two commercial nonionic surfactants, \(\hbox {Triton}^{{\circledR }}\) X-100 (commonly used but toxic) and sucrose laurate (environmentally friendly surfactant, biodegradable), were used at a concentration equal to 10 critical micelle concentration. Columns were first saturated with water and then flushed with 1.5 PV (pore volumes) of surfactant solution in order to achieve the adsorption of molecules into the soil matrix. Then, co-injection of air and surfactant solution was performed at a constant total rate to generate in situ foam. The quality of the foam was varied from 85 to 99 % to investigate the effect of this parameter on the resistance factor. A graphic showing the dependence of RF and the permeability is presented. Results suggest that for the same total flow rate, the RF decreases as permeability increases, but for permeabilities smaller than 1 Darcy, the RF is weak, probably due to the difficulty to generate stable foam under high capillary pressures. Variations in foam quality and surfactant type do not seem to have an important effect on the results regarding RF. The presented results are assistance for predicting foam behavior in porous media of different permeabilities.

Monitoring the Distribution of Surfactants in the Stratum Corneum by Combined ATR-FTIR and Tape-Stripping Experiments

Combined ATR-FTIR (attenuated total reflection-Fourier transform infrared) spectroscopy and tape-stripping experiments in vitro on porcine ear skin were used to investigate the spatial distribution of different surfactants in the stratum corneum (SC). To reveal a possible connection between the size of the formed micelles and skin penetration, dynamic light-scattering measurements of the aqueous surfactant solutions were also taken. Compared to an alkyl polyglycoside and sucrose laurate, a deeper skin penetration of the anionic surfactants sodium dodecyl sulfate (SDS) und sodium lauryl ether sulfate (SLES) could be related to a smaller size of the formed micelles. Beside the differences in spatial distribution, a link between the physical presence of anionic surfactants in the SC and a decrease of skin hydration was found. Furthermore, the incorporation of SDS and SLES into the SC, even after a brief, consumer-orientated washing procedure with commercially available hair shampoos, was confirmed.

Purification and improvement of the functional properties of Rhizopus oryzae lipase using immobilization techniques

The adsorption/immobilization of Rhizopus oryzae lipase (ROL) has permitted the development of several strategies to improve the properties of this industrial enzyme. The enzyme can be purified, immobilized, hyperactivated and stabilized, though its enantioselectivity could still be improved. A moderately hydrophobic support (e.g., phenyl-Toyopearl) allows the almost-quantitative immobilization of the enzyme via selective hydrophobic adsorption, while any contaminant proteins are not adsorbed. A further desorption of the adsorbed enzyme with surfactants (e.g., 0.5% sucrose laurate) allows the complete purification of the enzyme in only one step, with a 90% purification yield and an 8-fold purification factor. By using a more hydrophobic support, the ROL can be immobilized and hyperactivated. The enzyme is completely adsorbed on octyl-Sepharose and C18-Sepabeads. The pure enzyme (when adsorbed on these supports) becomes hyperactivated to approximately 250% of the activity of the soluble enzyme. In this study, two protocols for the covalent immobilization of ROL were developed: a one-point immobilization on CNBr-activated Sepharose and a multipoint covalent immobilization on highly activated glyoxyl-agarose supports. The multipoint attached enzyme decreased in activity to 50% of the activity of the soluble enzyme, but the derivatives were 300-fold more stable than the soluble enzyme. The hydrolysis of racemic 2-O-butyryl-2-phenylacetic acid was modulated by the different immobilized derivatives. In fact, the most active and selective preparation was demonstrated to be the C18-SB-ROL derivative (0.05UI/mg and E=22) when compared with the CNBr-ROL enzyme preparation (0.0073UI/mg and E=3.5).

Formulation of Microemulsions Based on Sugar Surfactant as an Alternative Fuel

Microemulsion systems that serve as water in diesel fuel were formulated using minimum amount of sucrose laurate at 25°C. Comparative experiments were also conducted using n-heptane. It was found that in order to formulate diesel and microemulsions a cosurfactant should be added. Alcohols such as 1-butanol,1-pentanol, 1-hexanol, and 1-heptanol served as cosurfactants. The area of the one-phase microemulsion region varies depending on the cosurfactant structure and composition. A continuous microemulsion region was observed with 1-butanol and 1-pentanol. Water solubilization capacity and thermodynamics as a function of alcohol chain length was determined.

Sucrose ester-based biocompatible microemulsions as vehicles for aceclofenac as a model drug: formulation approach using D-optimal mixture design

We assessed the functionality of sucrose esters (sucrose laurate, myristate, palmitate, and stearate), relatively innocuous nonionic surfactants, in formulation of biocompatible microemulsions. The putative influence of surfactant structure on the extension of microemulsion region was explored through the construction of the pseudo-ternary phase diagrams for the isopropyl myristate/sucrose ester-isopropyl alcohol/water system, using the titration method and mixture experimental approach. Minor changes in surfactant tail length strongly affected the microemulsion area boundaries. D-optimal mixture design proved to be highly applicable in detecting the microemulsion regions. Examination of conductivity, rheology, and thermal behavior of the selected sucrose laurate and sucrose myristate-based microemulsions, upon dilution with water, indicated existence of percolation threshold and suggested the phase inversion from water-in-oil to oil-in-water via a bicontinuous structure. Atomic force micrographs confirmed the suggested type of microemulsions and were valuable in further exploring their inner structure. The solubilization capacity of aceclofenac as a model drug has decreased as the water volume fraction in microemulsion increased. High surfactant concentration and the measured solubility of aceclofenac in microemulsion components suggested that the interfacial film may mostly contribute to aceclofenac solubilization.

Effects of propylene glycol alginate and sucrose esters on the physicochemical properties of modified starch-stabilized beverage emulsions.

This study was conducted to investigate the effect of main emulsion components namely, modified starch, propylene glycol alginate (PGA), sucrose laurate and sucrose stearate on creaming index, cloudiness, average droplet size and conductivity of soursop beverage emulsions. Generally, the use of different emulsifiers or a mixture of emulsifiers has a significant (p < 0.05) effect on the response variables studied. The addition of PGA had a significant (p < 0.05) effect on the creaming index at 55 °C, while PGA-stabilized (PGA1) emulsions showed low creaming stability at both 25 °C and 55 °C. Conversely, the utilization of PGA either as a mixture or sole emulsifier, showed significantly (p < 0.05) higher cloudiness, as larger average droplet size will affect the refractive index of the oil and aqueous phases. Additionally, the cloudiness was directly proportional to the mean droplet size of the dispersed phase. The inclusion of PGA into the formulation could have disrupted the properties of the interfacial film, thus resulting in larger droplet size. While unadsorbed ionized PGA could have contributed to higher conductivity of emulsions prepared at low pH. Generally, emulsions prepared using sucrose monoesters or as a mixture with modified starch emulsions have significantly (p < 0.05) lower creaming index and conductivity values, but higher cloudiness and average droplet size.

Appearance and distribution of regioisomers in metallo- and serine-protease-catalysed acylation of sucrose in N,N-dimethylformamide

Abstract The appearance and distribution of monoester regioisomers were investigated in the virtually irreversible acylation of sucrose with the enol ester, vinyl laurate, as acyl donor catalysed by serine proteases and a metalloprotease in the hydrophilic, aprotic solvent N , N -dimethylformamide. Sucrose laurate was obtained in yields from 12 to 53% after 48 h under different catalytic conditions. The serine protease ALP-901, derived from a Streptomyces sp., produced the highest yield at this reaction time, while reaction with the zinc-protease thermolysin achieved the overall highest yield (63%) after 6 h, with only monoesters synthesised. The total conversion of sucrose after 48 h ranged from 19 to 96%. The highest degree of conversion was observed in the reaction with thermolysin, while the reactions without protein and with ALP-901 resulted in 82% and 66% sucrose conversion, respectively. 2- O -Lauroyl sucrose was the most abundant monoester regioisomer synthesised and the highest concentration observed was 23.7 mM after 24 h in the thermolysin-catalysed reaction. The highest concentration of 2- O -lauroyl sucrose detected in the reaction catalysed by ALP-901 was 19.0 mM, while it was 17.0 mM the reaction without protein, both after 48 h. The detected appearance of the sucrose laurate regioisomers largely corresponded to the apparent rates of formation, and 2- O -lauroyl sucrose was among the first regioisomers to appear in all reactions. The observed sucrose laurate regioisomeric distribution after 48 h (2:3:4:6:1′:3′) was 72:5:2:1:7:14 in the reaction catalysed by ALP-901, and 74:5:2:1:7:13 in the reaction without protein. In the reaction catalysed by thermolysin the distribution was 71:5:2:–:9:13 after 6 h and 86:8:–:–:4:3 after 48 h of reaction. The esterification of sucrose with vinyl laurate without protein in the reaction mixture appeared to be catalysed in the presence of aluminosilicate molecular sieves. Non-catalytic protein in the reaction medium seemed to lower the catalytic activity of the molecular sieves.