硬脂酸对CeO2纳米粒子的表面修饰研究

利用表面修饰法合成了硬脂酸修饰的 CeO2 纳米粒子,采用透射电子显微镜(TEM)观察了经表面修饰的CeO2 纳米粒子的形貌及分散性,并采用红外光谱(IR)、紫外可见分光光度计等对修饰的CeO2 纳米粒子进行了表征。结果表明:表面修饰剂硬脂酸与 CeO2 纳米粒子表面之间发生了化学键合作用;修饰后的CeO2 纳米粒子表面存在疏水有机基团,阻隔了 CeO2 纳米粒子的团聚,起到了分散作用;同时,修饰后的CeO2 纳米粒子在苯乙烯中的稳定性得到了提高。并且获得了硬脂酸的修饰量与CeO2 纳米粒子的最佳配比。     

Proniosomal gel-mediated transdermal delivery of bromocriptine: in vitro and ex vivo evaluation

Vesicular systems endow large opportunities for the transdermal delivery of therapeutics. The present study was designed to investigate the potential of a novel class of vesicular system ‘proniosome’ as a carrier for transdermal delivery of bromocriptine (BCT). Proniosome formulations were prepared by the coacervation-phase separation method and the influence of factors like surfactant type and its amount, lipid concentration, cholesterol amount and drug content were studied. Span 60 was the most appropriate surfactant, and yielded vesicle size and percentage encapsulation efficiency of 1.3 µm and 98.9%, respectively. The developed system was characterised w.r.t. morphology, transition temperature, drug release, skin permeation and skin irritancy. Proniosomes exhibited a sustained release pattern of BCT in vitro. Skin permeation study revealed high penetration of proniosomes with sustained release of BCT through rat skin. The optimised proniosomal formulation showed enhanced transdermal flux of 16.15 μg/cm²/h as compared to 3.67 μg/cm²/h for drug dispersion. The developed formulations were observed as non-irritant to the rat skin and were found as quite stable at 4 and 25 °C for 90 days w.r.t. vesicle size and drug content. The dried proniosomal formulation could act as a promising alternative to niosomes and preferably for transdermal delivery of BCT.     

In vitro skin permeation and retention of paromomycin from liposomes for topical treatment of the cutaneous leishmaniasis

Paromomycin (PA), a very hydrophilic antibiotic, has been tested as an alternative topical treatment against cutaneous leishmaniasis (CL). Although this treatment has shown promising results, it has not been successful in accelerating the recovery in most cases. This could be attributed to the low skin penetration of PA. Liposomal formulations usually provide sustained and enhanced drug levels in skin. The aim of this study was to prepare liposomal formulations containing PA and to investigate their potential as topical delivery systems of this antileishmanial. Large multilamellar vesicles (MLVs) were prepared by conventional solvent evaporation method. Large unilamellar vesicles (LUVs) were prepared by reverse-phase evaporation method. The lipids used were soybean phosphatidylcholine (PC) and PC:cholesterol (CH) (molar ratio 1:1). The skin permeation experiments across stripped and normal hairless mice skin were performed in modified Franz diffusion cells. The PA entrapment in LUV liposomes (20.4 ± 2.2%) was higher than that observed for MLV liposomes (7.5 ± 0.9%). Drug entrapment was 41.9 ± 6.2% and 27.2 ± 2.4% for PC and PC:CH LUV, respectively. The skin permeation was 1.55 ± 0.31%, 1.29 ± 0.40%, 0.20 ± 0.08%, and 0.50 ± 0.19% for PC LUV, PC:CH LUV, empty LUV + PA and aqueous solution, respectively. Controlled topical delivery, across stripped skin, was observed for PA entrapped in LUV liposomes.     

硬脂酸修饰纳米TiO2颗粒的摩擦学性能研究

采用溶胶一凝胶法制备了硬脂酸表面修饰纳米TiO2颗粒，使用冷冻蚀刻电镜（FEEM）对其进行了形貌表征，用MM-WlA型四球试验机评价了其摩擦学性能，并考察了与硫化烯烃的复配规律。结果表明，所制备的纳米TiO2颗粒大小均匀，没有明显的团聚现象，在基础油中能起到极压抗磨作用，具有良好的极压性能，有利于提高油品的承载能力。另外，所制备的纳米TiO2添加剂与硫化烯烃有很好的复配效应，可以大幅度提高基础油的抗烧结负荷，这对于提高齿轮油的承载能力，具有非常重要的应用价值。     

硬脂酸填充碳纳米管相变胶囊材料的热性质研究

采用真空浸渗法,成功地将硬脂酸填充到碳纳米管(CNTs)空管内,得到CNTs/硬脂酸纳米相变胶囊材料。差示扫描量热分析表明,硬脂酸填充CNTs后,熔点下降了2.85℃,硬脂酸在CNTs内的体积填充度为31.9%。采用分子动力学方法深入研究硬脂酸在CNTs受限空间内的热性质。结果表明,在CNTs的纳米受限空间作用下,硬脂酸分子在CNTs内呈有序的环状分布,与CNTs的管壁距离保存在0.37nm。与纯硬脂酸相比,CNTs/硬脂酸的熔点降低,自扩散系数增加,导热系数比空CNTs下降32%~41%,为纯硬脂酸的117~159倍。     

硬脂酸溶胶凝胶法制备氧化镁纳米微粒的研究

以硬脂酸为分散剂，采用溶胶凝胶法研究了制备氧化镁纳米微粒的条件，探讨了分散剂用量，反应时间，反应温度，烧结温度和时间对产物粒径与转化率的影响，取得了最佳工艺条件，分别用红外光谱（IR），X射线射末衍射（XRD），透射电镜（TEM）和比表面积（BET）测定，对该纳米微粒的结构与性能进行了表征，结果表明：Mg(NO3)2与CH3（CH2）16COOH的摩尔配比控制在1：1，于90℃反应20min，在470℃热处理3h，得到立方相氧化镁钠米微粒，形貌为椭球体，分散性好，平均粒径约为36nm.     

In vitro studies on transdermal permeation of butorphanol

The influence of the donor vehicles pH and the addition of laurocapram or transkarbam 12 as permeation enhancers on the transdermal permeation of butorphanol through human skin were examined with the aim of finding out about its possible use in the transdermal delivery system. As the pH of the donor vehicles rises, the mean value of butorphanol skin fluxes declines; an exponential relationship of the means of butorphanol flux values against the pH of the buffered aqueous donor vehicles has been demonstrated. The presence of 1% of transkarbam 12 (T12) or 5% of laurocapram (LC), respectively, in an isopropylmyristate (IPM) donor vehicle increased transdermal fluxes of butorphanol almost 2.5 times (58.1 ± 5.7 μg cm^-2 hr^-1) or 1.5 times (36.4 ± 7.0 μg cm^-2 hr^-1), respectively, when compared to blank donors. Considering clinical and pharmacokinetic data on butorphanol, it is possible to expect that a transdermal preparation sized 20 cm² and possessing flux values ranging between 5.1 and 15.3 μg cm^-2 hr^-1 should be sufficient to achieve effective butorphanol transdermal fluxes, namely using IPM donors containing T12. In conclusion, butorphanol is a suitable candidate for transdermal administration and T12 is a very a suitable enhancer for it.     

Enhancement effect of p-menthane-3,8-diol on in vitro permeation of antipyrine and indomethacin through Yucatan micropig skin

The enhancing effect of p-menthane-3,8-diol (MDO) on skin permeation of antipyrine (ANP) and indomethacin (IM) through Yucatan micropig skin in vitro was compared with l-menthol. p-menthane-3,8-diol is a metabolite of l-menthol and has little odor. It is easy to combine the vehicle because of lower lipophilicity than l-menthol. All formulations contained 40% (v/v) ethanol. The permeation of ANP increased with MDO about three times that without enhancer by increasing ANP concentration in the skin. However, the MDO effect was about a quarter that of l-menthol. The permeation of IM with MDO was about 15 times that with no enhancer and it was almost the same as that with l-menthol. The lag time of permeation was not significantly changed by MDO, which was not so in the case of l-menthol. Skin concentration of IM increased about 11 times and six times with MDO and l-menthol, respectively. MDO and l-menthol partitioned to the skin relatively high concentrations, 5.9 and 2.5 mg/cm³, respectively. The solubility of IM in the skin was improved by MDO, and consequently, the permeation of IM was enhanced.     

The influence of chirality,physicochemical properties,and permeation enhancers on the transdermal permeation of amlodipine across rat skin

Purpose: This study was aimed at investigating the possible relationship between the physical properties and the permeation of S-amlodipine and RS-amlodipine and studying the possible enantioselectivity of permeation of amlodipine in the presence and absence of enhancers, such as terpene enhancers and ethanol. Method: The solubility of S-amlodipine and RS-amlodipine was measured using the shake-flask method. The thermodynamic properties were investigated by differential scanning calorimetry (DSC). The type of racemate amlodipine was investigated by DSC and Fourier transform infrared spectroscopy (FTIR). The permeability of racemate and enantiomers of amlodipine through rat epidermis in vitro was investigated using the modified Franz diffusion cell. Results: The aqueous solubility of S-amlodipine was higher than that of RS-amlodipine. The melting temperature and enthalpy of fusion of S-amlodipine were lower than those of RS-amlodipine. RS-amlodipine was a racemic compound. The permeation of the enantiomers of amlodipine from RS-amlodipine reservoir showed no significant differences in the presence and absence of enhancers, but the permeation of S-amlodipine from S-amlodipine reservoir was significantly higher than that of RS-amlodipine from RS-amlodipine reservoir 30% ethanol, 50% ethanol, and terpene enhancers could not influence the difference in permeation between S-amlodipine and RS-amlodipine, but 75% ethanol could reduce the difference. Conclusion: These results suggested that there was no enantioselectivity of the enantiomers of amlodipine from RS-amlodipine reservoir in the presence and absence of enhancers, but the differences in physical properties between S-amlodipine and RS-amlodipine led to the difference in permeation across rat skins.     

溶胶凝胶-微波加热技术制备Y2O3稳定ZrO2纳米粉体的研究

以硬脂酸为分散荆。采用溶胶凝胶-微波加热技术研究了制备Y2O3稳定ZrO2(YSZ)纳米粉体的条件与方法。分别用红外光谱(IR)、X射线粉末衍射(XRD)、透射电镜(TEM)、比表面积(BET)测定及电测量技术对该纳米粉体的结构与性能进行了表征。结果表明：在700℃以上微波处理得到立方相YSZ纳米粉体，其粒子分散性好，形貌为椭球体，平均粒径约为37nm，在480～980℃温度范围内呈现出良好的电导率，并且有较高的稳定性。     

In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based, water-soluble nail lacquer

Commercial antimycotic nail lacquers are commonly based on water-insoluble resins. The present study was aimed at evaluating a novel, experimental nail lacquer (P-3051, Polichem SA, Lugano, Switzerland) based on the water-soluble film-forming agent hydroxypropyl chitosan (HPCH). The in vitro permeation of ciclopirox (CPX) from P-3051 and from a commercial, water-insoluble lacquer based on a vinyl resin (Penlac™, Aventis Pharma), was investigated using thin membranes obtained from bovine hooves, an accepted model for human nails. Similar CPX permeation fluxes at steady state through the membranes, but significantly different lag times were observed for P-3051 and Penlac™, when these were tested as dry films. The formulations thus appeared to influence only the time required by CPX to saturate the membrane, and not the final drug concentration gradient in the membrane. Permeation experiments performed on the same membranes and on hairless mouse skin with P-3051 and with a similar, HPCH-free vehicle (ERV), both tested in liquid form, disproved the possibility that HPCH might act as a permeation enhancer for CPX in either substrate. The possible reasons for the greater efficiency of the HPCH vehicle in terms of CPX transfer from the vehicle itself to the keratin membrane are discussed. This effect might be tentatively attributed to a particular affinity of HPCH for the membrane, resulting in intimate contact and strong adhesion of the HPCH lacquer to the keratin substrate.     

On the characterization of medicated plasters containing NSAIDs according to novel indications of USP and EMA: adhesive property and in vitro skin permeation studies

This work aims to establish if the assays recently introduced by EMA (Guideline on quality of transdermal patches-draft) and USP (Specific tests for transdermal delivery systems) to characterize transdermal patches (TP) are suitable for medicated plasters (MP). Six approved MP differing for type and characteristics of adhesive and backing layer were selected and characterized in terms of adhesive performances by tack, shear adhesion, peel adhesion and release liner removal tests and in vitro skin permeation. As far as the adhesive properties are concerned, the major drawback is related to the measurement of shear adhesion of MP made of an adhesive hydrogel and/or a stretchable backing layer which could be solved by reducing the applied load. Moreover, a concern on the mass balance prescribed by EMA draft for the acceptance of the results of in vitro penetration studies remains. Indeed, the acceptance range is narrow than that reported by Ph. Eur. requirement for uniformity of content. Finally, a novel calculation for evaluating the in vitro efficiency of MP in releasing the loaded drug through the skin was proposed.     

Novel oleic acid derivatives enhance buccal permeation of didanosine

The aim of this study was to explore the potential of novel oleic acid (OA) derivatives as buccal permeation enhancers for the delivery of didanosine (ddI). The OA derivatives, i.e. ester derivative (OA1E), the dicarboxylic acid derivative (OA1A) and the bicephalous dianionic surfactant (OA1ANa) were synthesized and their effects were compared to the parent OA. OA, OA1E, OA1A and OA1ANa at 1%?w/w all showed potential for enhancing the buccal permeability of ddI with enhancement ratio (ER) of 1.29, 1.33, 1.01 and 1.72, respectively. OA1ANa at 1%?w/w demonstrated the highest flux (80.30?±?10.37?µg?cm^?2?h), permeability coefficient (4.01?±?0.57?×?10^?3?cm?h^?1) and ER (1.72). The highest flux for ddI (144.00?±?53.54?µg?cm^?2?h) was reported with OA1ANa 2%?w/w, which displayed an ER of 3.09 more than that with ddI alone. At equivalent concentrations, OA1ANa (ER?=?3.09) had a significantly higher permeation-enhancing effect than its parent OA (ER?=?1.54). Histomorphological studies confirmed that OA1ANa at all concentrations (0.5, 2.0 and 6.0%?w/w) had no adverse effects on the mucosae. Morphological changes such as vacuoles formation and increased intercellular spaces were attributed to the buccal permeation-enhancing effect of OA1ANa. This study demonstrated the potential of novel OA derivatives as buccal permeation enhancers. OA1ANa at 2%?w/w was also identified as the optimal novel OA derivative to widen the pool of fatty acid derivatives as chemical permeation enhancers for buccal drug delivery.     

Effect of application volume of ethanol-isopropyl myristate mixed solvent system on permeation of zidovudine and probenecid through rat skin

Permeation of zidovudine (AZT) and probenecid from an ethanol-isopropyl myristate (IPM) mixed system through rat skin was studied in a finite system. Several volume sizes of the ethanol-IPM mixed systems containing AZT and probenecid, both as suspensions, were applied on the skin of the hairless rat using a vertical glass cell, and the fractions of the drugs permeated in 8 hr Q_%,8hr were determined. For the systems containing 40% ethanol, the Q_%,8hr value decreased with the reduction of volume of the system applied, and the decreasing profile was similar to that calculated on the assumption that the permeability of the drug does not change with the volume of the sample applied. On the other hand, in the systems containing 10% or 20% ethanol, the Q_%,8hr value showed a maximum when a specific volume of the sample was applied. Therefore, the effect of sample volume on the Q_%,8hr value was different between the 40% ethanol-IPM system and the 10% or 20% ethanol-IPM system. Following pretreatment of the skin with 0.105 ml/cm² of drug-free 40% ethanol-IPM for 2 hr, several volume sizes of 10% ethanol-IPM systems containing the drugs were applied on the skin to explain why the different profiles were observed in the system containing 10% or 20% ethanol. The results for pretreated skin suggest that the amount of ethanol in the systems with low ethanol concentration and small application volume is too small to exert an effect that enhances permeation of the drugs. In those systems, the integrated effect of ethanol on the skin would be important for the enhancing effect. Total volume, as well as concentration, of an enhancer should be set precisely in designing an efficient transdermal delivery system.     

Topical delivery of fluconazole: in vitro skin penetration and permeation using emulsions as dosage forms

We investigated in vitro skin penetration and permeation of fluconazole from emulsions containing different penetration enhancers. Fluconazole permeation was high (15-65% of the applied dose) across hairless mouse skin and low (8-9%) across pig ear skin. Permeation across mice skin from a formulation containing propyleneglycol and isopropyl myristate was significantly higher than that observed with the paraffin oil and propyleneglycol or Transcutol® emulsions. With pig skin, the paraffin oil or isopropyl myristate and propyleneglycol emulsions showed similar skin permeation and penetration. However, these emulsions provided epidermal concentrations higher than the minimal inhibitory concentrations for most dermatophytes.     

Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity,solubility, and skin permeation studies

Background: Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein.

Method: Five different ILs were prepared—three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated.

Results: Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25?°C and 32?°C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine.

Conclusions: Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.     

超声辅助溶胶凝胶法制备硬脂酸/SiO2定形相变储能材料

在超声波的促进作用下, 以正硅酸乙酯为溶胶前驱体、 硬脂酸为相变组分, 经溶胶-凝胶过程制备了硬脂酸/SiO₂复合定形相变储能材料。为了研究硬脂酸/SiO₂复合定形相变储能材料的制备工艺, 考察了不同超声功率对材料制备过程中加强两相传质作用的辅助效果的影响以及不同种类催化剂对材料制备过程中溶胶-凝胶过程的影响, 最后确定出具有良好定形效果下材料的最大硬脂酸质量分数为60%。超声辅助酸碱复合催化法制备硬脂酸/SiO₂材料具有无需添加助溶剂和表面活性剂、 凝胶速度快、 方法简便的优点。对硬脂酸/SiO₂复合定形相变储能材料进行了FTIR结构表征和DSC、 TG热性能及热稳定性测试, 产品的相变焓值达91.46 J/g, 在低于175℃具有良好的热稳定性。      

In vitro assessment of acyclovir permeation across cell monolayers in the presence of absorption enhancers

The aim of the investigation was to establish transepithelial permeation of acyclovir across Caco-2 and Madin-Darby canine kidney (MDCK) cell monolayers and attempt to improve its permeation by employing absorption enhancers (dimethyl β cyclodextrin, chitosan hydrochloride and sodium lauryl sulfate) and combinations thereof. Caco-2 and MDCK cell monolayers have been widely employed in studying drug transport, mechanisms of drug transport, and screening of absorption enhancers and excipients. Transepithelial electrical resistance and permeation of ^99mTc-mannitol were employed as control parameters to assess the tight junction and paracellular integrity. Permeation of acyclovir in the presence of absorption enhancers was found to be significantly higher compared with drug permeation in their absence when assessed as apparent permeability coefficients (P_app). Synergistic improvements in P_app values of acyclovir were obtained in case-selected combinations of absorption enhancers; dimethyl β cyclodextrin-chitosan hydrochloride, chitosan hydrochloride-sodium lauryl sulfate, and dimethyl β cyclodextrin-sodium lauryl sulfate, were used. Recovery and viability assessment studies of both cell monolayers suggested reestablishment of paracellular integrity and no damage to cell membranes. Significantly improved permeation of acyclovir in the presence of selected combinations of absorption enhancers may be used as a viable approach in overcoming the problem of limited oral bioavailability of acyclovir.     

Removal of terephthalic acid in alkalized wastewater by ferric chloride

Terephthalic acid, which is a main component in alkali-decrement wastewater, is efficiently removed using ferric chloride in high pH solutions. About 90% removal of terephthalic acid is achieved at pH between 8 and 11. Especially, the removal reached 94.3% at pH 11. However, as the pH increased from pH 12 and 13, the low removal of terephthalic acid were found. The increasing ferric chloride dosage had a dramatic positive impact on the achieved removal of terephthalic acid. Further increase in the ferric chloride dosage did not produce better removal rate. The increase of terephthalic acid concentration also led to the increase of ferric chloride dosage in order to get the same removal of terephthalic acid. There was approximately a negative linear relationship between terephthalic acid concentration and removal of terephthalic acid. Compared with other coagulants, it can be seen that ferric chloride is more effective in a high pH solution and the amount of ferric chloride required is also less as compared with aluminum chloride, magnesium chloride and calcium chloride. Our results clearly showed that terephthalate anions strongly binds to positive Fe(OH)(3) flocs and forms insoluble complexes, probably through a mechanism involving electrostatic attraction. The electrostatic attraction may be particularly useful means of purifying wastewater in high pH solutions.     

Vesicles composed of fatty acid and N-[3-(dimethylamino)propyl]-octadecanamide: effect of fatty acid chain length on physicochemical properties of vesicles

Background and objectives: Vesicles, recently claimed as drug delivery carriers, were prepared by taking advantage of an electrostatic interaction between the carboxylic groups of fatty acids (FAs) and the amino groups of N-[3-(Dimethylamino)propyl]-Octadecanamide (DMAPODA). The study is to find out the effect of FAs' chain length on physicochemical properties of vesicles.

Methods: Decanoic acid (DA), myristic acid (MA), stearic acid (SA) and behenic acid (BA) were used as FAs. Vesicles composed of them and DMAPODA were studied about formation on microscope, calorimetric analysis, size and zeta potential.

Results: On microphotographs, all of FAs could form vesicles when mixed with DMAPODA in an equi-molar ratio. However, DA/DMAPODA vesicles were disintegrated during the homogenization. Due to the asymmetry of DA/DMAPODA associate, it seems to hardly form a stable and well-packed bilayer. On thermograms, the vesicles exhibited one strong peak, indicating that FAs can be homogeneously mixed with the cationic amphiphile. The sizes of the four kinds of vesicles suspended in an aqueous solution (final pH?7.5) were in the same order (hundreds of nanometer) on microphotographs. But, on a light scattering machine, the mean size of MA/DMAPODA vesicle was measured to be much greater than those of the other vesicles, possibly because of the low absolute value of the zeta potential. In addition, the medium pH value had a significant effect on the size of BA/DMAPODA vesicle possibly because the zeta potential was strongly dependent on the pH value.

Conclusion: FAs' chain length would affect the physicochemical properties of vesicles composed of them and DMAPODA.