Carbopols as factors buffering triethanolamine interacting with artificial skin sebum

Triethanolamine is an ethanolamine applied as counter-ion for fatty acid soaps. Interaction between triethanolamine and free fatty acids is suggested to be useful for cleansing sebaceous follicles in acne prevention. Considering relatively high pH of aqueous triethanolamine solutions we investigated influence of different concentrations of anionic polymers--Carbopol 934P, Carbopol 974P and Carbopol 980 on pH, rheological behavior and, most of them, intensity of triethanolamine interaction with artificial skin sebum components. Triethanolamine buffered using Carbopols influenced artificial skin sebum. Intensity of this interaction was measured applying specific optical method. Penetration of triethanolamine into artificial sebum and its uplift induced by above mentioned interaction were measured. Respective penetration rates and uplift rates were calculated. We found significant differences between Carbopols. The values of the penetration rates amounted 2.94 x 10(-04) h(-1) to 4.12 x 10(-03) h(-1), whereas rates for the uplift process were from 1.97 x 10(-04) h(-1) to 3.28 x 10(-03) h(-1). The value of pH is reduced from 10.06 for pure 0.1 M aqueous triethanolamine solution to 7.67 with the increase of polymer to triethanolamine molar ratio in the preparations. It is considered that triethanolamin buffered with acrylic acid polymers--Carbopols could influence cleansing of pilosebaceous unit follicles and contribute to acne prevention.     

Preliminary assessment of alginic acid as a factor buffering triethanolamine interacting with artificial skin sebum.

Triethanolamine is an ethanolamine used as counter-ion for fatty acid soaps. Interaction between triethanolamine and free fatty acids is suggested to be useful for cleansing sebaceous follicles in acne prevention. This study describes the preliminary assessment of alginic acid as a factor buffering triethanolamine interacting with stearic acid--a compound of artificial skin sebum. Penetration of triethanolamine into artificial sebum, induced by the above mentioned interaction, was measured using a specific optical method. The values of the penetration depth amounted to 0.07-5.74 mm. pH values were measured. The value of pH is reduced from 10.06 for pure 1.49% (w/w) aqueous triethanolamine solution to 6.61 with the increase of the alginic acid to triethanolamine ratio in the preparations. The data of this in vitro research will support further study on other anionic polymers as factors buffering ethanolamines penetrating artificial skin sebum.     

Comparison of artificial sebum with human and hamster sebum samples

To understand drug delivery to the sebum filled hair and sebaceous follicles, it is essential to use an artificial sebum as a surrogate of the human sebum for the investigation of drug transport properties. Artificial sebum L was developed in-house based on the chemical similarity to human sebum. The partition and diffusion of model compounds (ethyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate, and hexyl 4-hydroxybenzoate) were measured in human sebum, hamster ear and body sebum (a commonly used animal model), and four representative artificial sebum samples (N, S, F, and L) in which artificial sebums, N, S and F were selected based on the available literature. DSC and NMR studies were also conducted on all sebums to compare their melting properties and chemical compositions. In vitro studies show that the partition coefficients of the three model compounds in artificial sebum L were similar to that of human sebum, whereas the hamster ear and body sebum, and other three artificial sebum samples were different from that of human sebum. Additionally, the in vitro sebum flux (microg/(cm(2)min) of three model compounds through artificial sebum L was closer to that of human sebum when compared with the other three artificial sebum (N, S and F), hamster body and hamster ear sebum. The results of this study indicate that the artificial sebum L could be used as an alternative to human sebum, as the physicochemical properties of this artificial sebum is relatively similar to human sebum.     

Optimization of methacrylic acid ester copolymers blends as controlled release coatings using response surface methodology

The aim of this study was to statistically optimize the use of blends of methacrylic acid ester copolymers with different permeability properties as controlled-release coating systems for tablets to produce predictable predesigned release profiles. A full factorial design was used to study and optimize the use of methacrylic acid ester copolymers Eudragit RS 30D and Eudragit RL 30D as coating materials for controlled release. Directly compressed theophylline tablets were coated with aqueous dispersions containing different proportions of the two copolymers using a side-vented coating pan (Accela Cota). The effect of polymer loading level at 5, 7.5, and 10% weight gain and curing time at 50 degrees C for 12 and 24 hours were also evaluated. Coated tablets were tested for their drug release in water using a United States Pharmacopeia (USP) dissolution apparatus #2. The results showed that increasing the content of the lower permeability copolymer Eudragit RS 30D, increasing the polymer load, and increasing curing time at 50 degrees C resulted in slower drug release. A statistical model that describes and predicts the drug release properties of the coated tablets as a function of the copolymers ratio in the coating dispersion, polymer load, and curing time at 50 degrees C was developed. The most significant factor affecting drug release was found to be the ratio of the two copolymers in the coating dispersion followed by the curing time at 50 degrees C and the polymer loading level. Good correlations were observed between the model fitted values andthe experimental values. An optimized formula prepared by superimposing two-dimensional contour plots was prepared; its release profile was found to be in agreement with the prediction obtained from the model.     

Preliminary assessment of the skin sensitizing activity of selected rodent carcinogens using the local lymph node assay

It has been demonstrated previously that there exists an incomplete correlation between the skin sensitizing potential of chemicals and their mutagenic properties as judged by activity in the Salmonella mutation assay. More recently, it has been proposed that there may exist a broader association between carcinogenicity in rodents (including non-genotoxic carcinogenesis) and skin sensitizing activity. To explore further these putative relationships we have here examined the skin sensitizing potential of two non-genotoxic rodent carcinogens which are generally considered not to represent a carcinogenic hazard in humans (limonene and saccharin) and of three genotoxic rodent carcinogens (vinylidene dichloride, ethyl acrylate and bisphenol A diglycidyl ether). For this purpose we have used the local lymph node assay (LLNA), a method for the identification and characterization of skin sensitizing chemicals that has recently been recognized as a stand-alone method for hazard identification purposes. Activity in the LLNA was compared with the results of Salmonella tests conducted previously. This small series of investigations reveals that there exists no general relationship between skin sensitizing potential and rodent carcinogenicity. Furthermore, although a general correlation does exist between mutagenic activity and skin sensitization, this association is not universal and activity in the Salmonella mutation assay does not necessarily imply skin sensitizing potential. Collectively these data suggest that it is inappropriate currently to recommend the use of skin sensitization tests as an adjunct to conventional approaches to the evaluation of potential carcinogenicity.     

On the role of methacrylic acid copolymers in the intracellular delivery of antisense oligonucleotides.

The delivery of active biomacromolecules to the cytoplasm is a major challenge as it is generally hindered by the endosomal/lysosomal barrier. Synthetic titratable polyanions can overcome this barrier by destabilizing membrane bilayers at pH values typically found in endosomes. This study investigates how anionic polyelectrolytes can enhance the cytoplasmic delivery of an antisense oligonucleotide (ODN). Novel methacrylic acid (MAA) copolymers were examined for their pH-sensitive properties and ability to destabilize cell membranes in a pH-dependent manner. Ternary complex formulations prepared with the ODN, a cationic lipid and a MAA copolymer were systematically characterized with respect to their size, zeta potential, antisense activity, cytotoxicity and cellular uptake using the A549 human lung carcinoma cell line. The MAA copolymer substantially increased the activity of the antisense ODN in inhibiting the expression of protein kinase C-alpha. Uptake, cytotoxicity and antisense activity were strongly dependent on copolymer concentration. Metabolic inhibitors demonstrated that endocytosis was the major internalization pathway of the complexes, and that endosomal acidification was essential for ODN activity. Confocal microscopy analysis of cells incubated with fluorescently-labeled complexes revealed selective delivery of the ODN, but not of the copolymer, to the cytoplasm/nucleus. This study provides new insight into the mechanisms of intracellular delivery of macromolecular drugs, using synthetic anionic polyelectrolytes.     

Complexes of aminoglycoside antibiotics with copolymers of acrylamide with acrylic and methacrylic acids

Polymer complexes of aminoglycoside antibiotics as bases with low molecular weight water-soluble copolymers of acrylamide (ACR) with acrylic (AA) and methacrylic (MA) acids containing 15 – 20 mol% carboxyl groups were synthesized. Complexes of antibiotics with ACR-MA copolymers were found to be more stable in aqueous and aqueous salt solutions and to have less toxicity in vitro than complexes based on ACR-AA copolymers. All polymer complexes retained high levels of antibacterial activity.     

Polymeric micelles based on poly(methacrylic acid) block-containing copolymers with different membrane destabilizing properties for cellular drug delivery

Poly(methacrylic acid)-b-poly(ethylene oxide) are double hydrophilic block copolymers, which are able to form micelles by complexation with a counter-polycation, such as poly-l-lysine. A study was carried out on the ability of the copolymers to interact with model membranes as a function of their molecular weights and as a function of pH. Different behaviors were observed: high molecular weight copolymers respect the membrane integrity, whereas low molecular weight copolymers with a well-chosen asymmetry degree can induce a membrane alteration. Hence by choosing the appropriate molecular weight, micelles with distinct membrane interaction behaviors can be obtained leading to different intracellular traffics with or without endosomal escape, making them interesting tools for cell engineering. Especially micelles constituted of low molecular weight copolymers could exhibit the endosomal escape property, which opens vast therapeutic applications. Moreover micelles possess a homogeneous nanometric size and show variable properties of disassembly at acidic pH, of stability in physiological conditions, and finally of cyto-tolerance.     

Evaluation of the deformation behavior of binary systems of methacrylic acid copolymers and hydroxypropyl methylcellulose using a compaction simulator

Methacrylic acid copolymers have been shown to enhance release of weakly basic drugs from rate controlling polymer matrices through the mechanism of microenvironmental pH modulation. Since these matrices are typically formed through a compaction process, an understanding of the deformation behavior of these polymers in there neat form and in combination with rate controlling polymers such as HPMC is critical to their successful formulation. Binary mixes of two methacrylic acid copolymers, Eudragit L100 and L100-55 in combination with HPMC K4M were subjected to compaction studies on a compaction simulator. The deformation behavior of the powder mixes was analyzed based on pressure-porosity relationships, strain rate sensitivity (SRS), residual die wall force data and work of compaction. Methacrylic acid copolymers, L100-55 and L-100 and the hydrophilic polymer, HPMC K4M exhibited Heckel plots representative of plastic deformation although L-100 exhibited significantly greater resistance to densification as evident from the high yield pressure values ( approximately 120MPa). The yield pressures for the binary mixes were linearly related to the weight fractions of the components. All powder mixes exhibited significant speed sensitivity with SRS values ranging from 21.7% to 42.4%. The residual die-wall pressures indicated that at slow speeds (1mm/s) and at lower pressures (<150MPa), HPMC possesses significant elastic behavior. However, the good compacts formed at this punch speed indicate significant plastic deformation and bond formation which is able to predominate over the elastic recovery component. The apparent mean yield pressure values, the residual die-wall forces and the net work of compaction exhibited a linear relationship with mixture composition, thereby indicating predictability of these parameters based on the behavior of the neat materials.     

Preliminary assessment of atmospheric methylcyclopentadienyl manganese tricarbonyl and particulate manganese in selected urban sites

Methylcyclopentadienyl manganese tricarbonyl (MMT: C9H7MnO3) is an organometallic additive that has been used since 1976 as an octane enhancer in Canadian unleaded gasoline. Very few studies have determined its atmospheric concentrations and only one study offers recent data on its ambient level. This preliminary study aims to assess atmospheric concentrations of MMT and respirable and total Mn (Mn(R) and Mn(T) in selected sites, at two underground car parks and one gasoline station, related to high levels of automobile traffic. It is also an investigation of the applicability of the current analytical method. In total, 34 air samples were collected using a Gil-Air portable pump during 4 consecutive days and then were analyzed by neutron activation analysis. The concentrations vary between 40 and 104 ng/m3 for Mn(R), 146 and 204 ng/m3 for Mn(T) and 6 and 128 ng/m3 for MMT (including ultrafine particulates, Mn(UF). Of the 12 Mn(R) results, 7 showed concentrations greater than the U.S. EPA reference concentration (RfC = 50 ng/m3). The ratios of Mn(R) to Mn(T) varied from 0.20 to 0.65 with a mean of 0.38. The results for MMT and Mn(UF) raise serious doubts about the specificity of the sampling and chemical analysis methodology proposed by the Occupational Safety and Health Administration (OSHA) for MMT in air.     

Study of ascorbic acid interaction with hydroxypropyl-beta-cyclodextrin and triethanolamine, separately and in combination

Complexation between ascorbic acid, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and triethanolamine (TEA), separately and in combination, was studied in solution and solid state. The freeze-drying method was used to prepare solid complexes, while physical mixtures being obtained by simple blending. These complexes were characterized in the solid state using differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Nuclear magnetic resonance spectroscopy ((1)H and (13)C NMR) was used in aqueous solutions to obtain information about the mode of interaction. The degradation rate of each complex in solution was determined, and the stability constant of the complexes and the degradation rate of the ascorbic acid within the complexes were obtained. NMR studies provided clear evidence of partial inclusion into the HP-beta-CD cavity, but the stability constant value was very small indicating a weak host-guest interaction. The influence of complexation on the degradation rate of ascorbic acid was evaluated, and the data obtained showed a pronounced enhancement of aqueous stability with the TEA association complex, while this effect was lower with the HP-beta-CD inclusion complex. NMR experiments showed evidence of the formation of aggregates.     

Preliminary assessment of carrageenan as excipient for extrusion/spheronisation.

The current study pursues the suitability of different types of carrageenan as a novel extrusion aid. The aim was to find out a suitable substitution to the commonly used microcrystalline cellulose (MCC). The types of kappa-carrageenan were found to be the most appropriate material and the required fraction to produce acceptable pellets in the formulation was determined. The investigation showed that 5% of kappa-carageenan was necessary to produce pellets without MCC. Similar formulations produced with MCC or kappa-carrageenan were compared with respect to size and shape of the pellets. kappa-Carrageenan required higher water content for the formation of pellets, but the formulation was more robust as the optimal range of water content was much broader. Hence, kappa-Carrageenan seems to be a suitable and promising extrusion aid. The study showed that the substitution of MCC by kappa-carrageenan in formulations is possible and the produced pellets were of high quality.     

Safety assessment of myristic acid as a food ingredient.

Myristic acid is used in the food industry as a flavor ingredient. It is found widely distributed in fats throughout the plant and animal kingdom, including common human foodstuffs, such as nutmeg. Myristic acid (a 14-carbon, straight-chain saturated fatty acid) has been shown to have a low order of acute oral toxicity in rodents. It may be irritating in pure form to skin and eyes under exaggerated exposure conditions, but is not known or predicted to induce sensitization responses. Myristic acid did not induce a mutagenic response in either bacterial or mammalian systems in vitro. Relevant subchronic toxicity data are available on closely related fatty acid analogs. In particular, a NOEL of >6000mg/kg was reported for lauric acid (a 12-carbon, straight-chain saturated fatty acid) following dietary exposure to male rats for 18 weeks and a NOEL of >5000mg/kg was reported for palmitic acid (a 16-carbon, straight-chain saturated fatty acid) following dietary exposure to rats for 150 days. The data and information that are available indicate that at the current level of intake, food flavoring use of myristic acid does not pose a health risk to humans.     

肌肉减少症评价肝硬化患者营养状况及其影响因素

目的比较肌肉减少症与传统营养评价方法评估肝硬化患者营养状况,并进一步探讨肝硬化患者影响肌肉减少症发生的因素。方法收集2016年1月至2017年1月我科肝硬化患者资料,比较应用主观全面评价法(SGA)评分、传统营养指标及通过第3腰椎平面CT图像计算第3腰椎骨骼肌质量指数评估肝硬化患者的营养不良发生率。同时将52例肝硬化患者分为肌肉减少症组和非肌肉减少症组,分析2组间各营养指标有无差异,并进一步采用二分类Logistic回归分析法筛选影响肌肉减少症发生的危险因素。结果 52例肝硬化患者肌肉减少症的发生率为64%,2组患者年龄、性别、体质量指数(BMI)、血清白蛋白(ALB)、三头肌皮褶厚度(TSF)、上臂肌围(AMC)差异均有统计学意义(P<0.05)。二分类Logistic回归分析结果示:性别[OR=0.001,95%CI(0.000,0.223),P=0.011]、BMI[OR=0.312,95%CI(0.134,0.722),P=0.007]是肌肉减少症发生的主要危险因素。结论应用肌肉减少症可较客观地评估肝硬化患者的营养状况,且男性肝硬化患者,BMI越低,越容易发生肌肉减少症。     

Preliminary safety assessment of disodium etidronate as an additive to experimental oral hygiene products

Disodium etidronate is an effective anticalculus agent and is being considered for inclusion in toothpaste and mouthwash formulations. Disodium etidronate and products containing disodium etidronate were investigated for acute and subchronic toxicity and primary irritation potential.     

Controlled release of epidermal growth factor (egf) from egf-loaded polymeric nanoparticles composed of polystyrene as core and poly(methacrylic acid) as coronain vitro

Polymeric nanoparticles composed of polystyrene (PS) as core and poly(methacrylic acid) (PMA) as corona were prepared by the dispersion copolymerization. The potential of the nanoparticles as carriers for recombinant human epidermal growth factor (EGF) was investigated. The nanoparticles showed monodispersity and good water-dispersibility. The loading content of EGF to the nanoparticles was very high due to electrostatic interaction between EGF and nanoparticles. EGF was released as a pseudo-zero order pattern after initial burst effect. The nanoparticles were sufficient for A431 cells proliferation.