Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil

Objective: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions.

Methods: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin.

Results: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0?±?1.7% and 46.0?±?1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4?months at room temperature and at 4?°C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution.

Conclusion: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.     

Topical delivery of paclitaxel for treatment of skin cancer

Context: Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach.

Objective: The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma.

Methods: The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study.

Results: The particle size distribution was found to be in the range of 78.82–587.8?nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (J_ss), permeability coefficient (K_p), and enhancement ratio were significantly increased in SLN-loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer.

Conclusion: The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects.     

Physicochemical studies of binary eutectic of ibuprofen and ketoprofen for enhanced transdermal drug delivery

Methods: The thermodynamic, eutectic, and crystalline properties of ibuprofen and ketoprofen binary mixtures were investigated using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD). Results: The DSC studies showed that melting point (61°C), enthalpy (11.3 kJ/mol), and entropy of fusion (33.7 J/K/mol) of the binary eutectic were significantly lower than those of the individual anti-inflammatory drugs (NSAIDs). Due to the melting-point depression and enhanced skin lipid solubility, the steady-state flux of ibuprofen and ketoprofen from preparations of the binary eutectic increased as compared to pure NSAIDs using shed snakeskin as a model membrane. The NSAID membrane flux values were calculated by flux ratio equations based on drug thermodynamic data, and compared to experimental values obtained from permeation studies. Conclusion: The proposed flux ratio equations correctly predicted flux increase.     

Different trends for preparation of budesonide pellets with enhanced dissolution rate

The current research attempts different approaches to overcome the poor dissolution of budesonide (a poorly water-soluble drug) from pellet formulations. Various methods such as liqui-pellet (LP) and pellets made of solid dispersion (SDP) were employed and compared to conventional pellets (CP). In SDP method, budesonide:PVP solid dispersion was prepared followed by extrusion-pelletization. Solid dispersion of budesonide-PVP was also layered to the surface of placebo pellets (LSDP). In LP technique, budesonide dispersed in PEG 400 was mixed with Avicel or Avicel:lactose and was extruded-spheronized. Pellets were evaluated for their shape, size, mechanical properties and dissolution rate. The pellets made by LSDP method were significantly harder than CP or PSDP. LP with a loading factor greater than 0.34 was very soft compared to CP and SDP. Pelletization of budesonide SD (PSDP) did not have a tremendous effect on the dissolution enhancement of budesonide compared to CP whilst LSDP showed faster drug release. In conclusion, the layering of budesonide solid dispersion on placebo pellets (LSDP) was the most promising approach for the production of pellets with the highest dissolution rate so that more than 80% of the drug was released within the first 5 min. Also this formulation had proper mechanical properties. This method has the capability to overcome the poor dissolution of budesonide associated with the pellet containing Avicel, and could be employed for the dissolution enhancement of other poorly water-soluble drugs in pellet form.     

Simple preparation of photothermal nanomaterial GNR@SiO2 with enhanced drug loading content

With the rising threat of cancers, gold nanorods (GNRs) based photothermal–chemotherapy is becoming an increasingly important strategy to cure cancers. There are some challenges faced by GNRs system including complicated synthesis process and low drug loading capacity. In this study, GNRs assisted mesoporous silica nanoparticles (GNR@SiO₂ NPs) are fabricated by a simple method. The mesoporous SiO₂ can not only prevent the aggregation of GNRs but also provide large hollow mesoporous structure to enhance drug loading capacity. Moreover, GNRs absorb near‐infrared (NIR) light and convert it into heat. The temperature of the GNR@SiO₂ solution was increased to ∼60 (2 W) and 90°C (3 W) after NIR radiation. The photothermal conversion efficiency was 32.60% of GNR@SiO₂ under NIR light irradiation at 2 W, while 39.01% under NIR light irradiation at 3 W. The drug loading content of GNR@SiO₂ was 22.3 ± 2.5%, which was higher than that of most reported GNR drug delivery systems. The authors also found that the GNR@SiO₂ @ doxorubicin may have a higher drug release rate under the conditions of the tumour microenvironment. The in vitro cytotoxity of GNR@SiO₂ was demonstrated on HeLa cells. The experimental results indicate that GNR@SiO₂ has great potential for synergistic treatment to kill cancer cells.Inspec keywords: nanomedicine, cancer, nanofabrication, nanoparticles, silicon compounds, nanorods, cellular biophysics, photothermal effects, drug delivery systems, toxicology, biomedical materials, drugs, mesoporous materials, tumours, gold, biothermicsOther keywords: enhanced drug loading content, NIR light irradiation, GNR drug delivery systems, complicated synthesis process, drug loading capacity, mesoporous silica nanoparticles, photothermal nanomaterial, gold nanorods, photothermal–chemotherapy, SiO₂ , efficiency 39.01 percent, efficiency 32.60 percent, power 3.0 W, power 2.0 W, temperature 90.0 degC, cancer cells, HeLa cells, in vitro cytotoxity, tumour microenvironment, drug release rate, doxorubicin, photothermal conversion efficiency, aggregation     

Designing amorphous formulations of polyphenols with naringin by spray-drying for enhanced solubility and permeability

Naringin (NAR), a major flavanone (FVA) glycoside, is a component of food mainly obtained from grapefruit. We used NAR as a food additive to improve the solubility and permeability of hydrophobic polyphenols used as supplements in the food industry. The spray-dried particles (SDPs) of NAR alone show an amorphous state with a glass transition temperature (T_g) at 93.2 °C. SDPs of hydrophobic polyphenols, such as flavone (FVO), quercetin (QCT), naringenin (NRG), and resveratrol (RVT) were prepared by adding varying amounts of NAR. All SDPs of hydrophobic polyphenols with added NAR were in an amorphous state with a single T_g, but SDPs of hydrophobic polyphenols without added NAR showed diffraction peaks derived from each crystal. The SDPs with NAR could keep an amorphous state after storage at a high humidity condition for one month, except for SDPs of RVT/NAR. SDPs with NAR enhanced the solubility of hydrophobic polyphenols, especially NRG solubility, which was enhanced more than 9 times compared to NRG crystal. The enhanced solubility resulted in the increased membrane permeability of NRG. The antioxidant effect of the hydrophobic NRG was also enhanced by the synergetic effect of NAR. The findings demonstrated that NAR could be used as a food additive to enhance the solubility and membrane permeability of hydrophobic polyphenols.     

Optimization of nutraceutical coenzyme Q10 nanoemulsion with improved skin permeability and anti-wrinkle efficiency

Coenzyme Q10 (CoQ10) is an insoluble, poorly permeable antioxidant with great biological value which acts as anti-aging and anti-wrinkle agent. To improve its permeability through topical application, the current study aimed at formulating oil/water (o/w) nanoemulsion (NE) as an efficient vehicle for delivering (CoQ10) through the skin barriers. The solubility of (CoQ10) was tested for various oils, surfactants (S), and co-surfactants (CoS). The NE region was determined by constructing pseudoternary phase diagrams. NE formulae containing 1, 2, and 3% w/w drug have been subjected to thermodynamic stability test. The formulae that passed thermodynamic stability tests were characterized by physical properties as pH, viscosity, refractive index, droplet size, zeta-potential, TEM, electroconductivity, in vitro release, and ex vivo permeation. The formula ‘F2’ containing 10% w/w isopropyl myristate (oil phase), 60% w/w of Tween 80: Transcutol HP mixture (S/CoS_mix) at ratio 2:1, 30% w/w water and 2% w/w drug was evaluated for its anti-wrinkle efficiency using an animal model. The ‘F2’ formula showed 11.76?±?1.1?nm droplet size, 1.4260?±?0.0016 refractive index, 0.228 PDI, ?14.7?±?1.23?mv zeta potential, 7.06?±?0.051?pH, 199.05?±?0.35?cp viscosity, and the highest percentage of drug release in the selected dissolution media. About 47.21% of the drug was released in phosphate buffer 7.4 containing 5% w/v Labrasol and 5% w/v isopropyl alcohol through 24?h. It also showed the highest drug flux (J_ss?=?3.164?µg/cm²/h), enhancement ratio (E_r?=?8.32), and permeability coefficient (K_p?=?22.14?×?10^?4 cm²/h). CoQ10 NE reduced the skin wrinkles and gave the skin smooth appearance. Our investigation suggests the potential use of NE as a vehicle for enhancing solubility and permeability of CoQ10 and thus improving its anti-wrinkle efficiency.     

Facile preparation of Ce-doped TiO2/diatomite granular composite with enhanced photocatalytic activity

Granule-shaped Ce-doped TiO₂/diatomite (GCTD) hybrid was prepared via sol-gel method. The physicochemical properties of this hybrid were characterized by various analytical methods. As carrier, diatomite was conducive to the dispersion of TiO₂ nanoparticles, hindering their agglomeration process. Compared to TiO₂, GCTD showed visible-light-driven photoactivity, which was evaluated by the degradation of oxytetracycline (OTC) and disinfection of three bacteria (Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia) under visible light. The porous diatomite enhanced the photoactivity of TiO₂ via the adsorption towards target pollutants. The reusability experiment was conducted for 5 times, and the results showed that GCTD exhibited good photo-stability and reusability.     

FeSiCrB amorphous soft magnetic composites filled with Co2Z hexaferrites for enhanced effective permeability

Z-type Sr₃Co₂Fe₂₄O₄₁ hexaferrites (Co₂Z hexaferrites) were synthesized with sol–gel method and were mechanically mixed with spherical Fe₈₈Si₇Cr_2.5B_2.5 (FeSiCrB) amorphous powders, and then compacted to form toroidal Co₂Z hexaferrites/FeSiCrB amorphous soft magnetic composites (Co₂Z/FeSiCrB SMCs). The compositions, morphology and soft magnetic performance were characterized through SEM, XRD, VSM, EDS, B-H analyzer and impedance analyzer. All results reveal that Co₂Z hexaferrites in Co₂Z/FeSiCrB SMCs should mainly exist in air gaps between spherical FeSiCrB amorphous powders, leading to the increasing density. Saturation magnetization decreases a little for magnetic dilution and coercivity increases for the stronger magnetic interaction of Co₂Z/FeSiCrB SMCs. The introduction of Co₂Z hexaferrites in air gaps increases the conduction area of magnetic circuits and decreases the demagnetization effect, leading to the higher effective permeability of 27.4 for Co₂Z/FeSiCrB SMCs, much higher than 25.0 for FeSiCrB SMCs. Furthermore, Co₂Z/FeSiCrB SMCs present the smaller core loss and more stable DC bias characteristics owing to the insulating Co₂Z hexaferrites.     

用稻草秸秆制备高气密性增强膜及其性能研究

将稻草经清洗、蒸汽爆破、粉碎等工艺处理后,在100℃条件下用离子液溶解稻草粉末,得到秸秆溶液,采用延流法制得了秸秆膜,并选用棉织物作增强基材,将制得的秸秆溶液与棉织物复合,冷却洗净,去除离子液后晾干,得到高气密性增强膜.分析了秸秆膜的化学成分,结果表明,其保留了原稻草秸秆的主要化学成分,且含量相差不大.还对增强膜与秸秆膜进行了表面形态、回潮率、透湿性能、透气性能、力学性能研究对比,研究结果表明,秸秆液在棉织物表面形成无界面致密膜,这种增强膜具有高气密性、强吸湿性、较好的力学性能.     

Heparin decreases permeability of pig urinary bladder wall preliminarily enhanced by chitosan

Chitosan significantly increases the permeability of the isolated pig urinary bladder wall by causing urothelial desquamation, the extent of which depends also on the concentration of the polymer. By desquamation permeability barriers of the urothelium are removed. To gain additional insight into the mechanism by which chitosan acts an absorption enhancer into urinary bladder mucosa, we evaluated the influence of a polysaccharide heparin on the permeability of isolated pig urinary bladder wall preliminarily treated with chitosan. Moreover, we aimed to establish whether the effect of heparin depends on its concentration and on the degree of urothelial desquamation caused by chitosan. In the permeability studies performed by the use of diffusion cells, transport of a model drug, pipemidic acid, into the isolated pig urinary bladder wall was determined. Heparin did not have a significant effect on the permeability of the intact urothelium. When applied to the urinary bladder wall, whose permeability was preliminarily enhanced by 0.005% or 0.001% w/v chitosan, heparin decreased the permeation of pipemidic acid into the bladder wall to a level not significantly different from the intact tissue. However, the effect of heparin was not significant at the highest concentration of chitosan tested, where the damage to the urothelium was much more intense compared with that found at lower concentrations of the polymer. The formation of complexes between pipemidic acid and heparin cannot be excluded completely, but it seems that they are not the main reason for the decreased permeation of pipemidic acid in the presence of heparin. By application on the urothelium, damaged by chitosan, heparin is supposed to form a layer on the surface of the urothelium that prevents the transport of the model drug into the bladder wall. In this way heparin probably restores the impermeability properties of the urinary bladder wall to a degree dependent on the urothelial damage.     

Tyrosine-assisted preparation of Ag/ZnO nanocomposites with enhanced photocatalytic performance and synergistic antibacterial activities

In this paper, Ag/ZnO metal-semiconductor nanocomposites were prepared through a facile one-pot hydrothermal method with the assistance of tyrosine. The synthesized samples were structurally characterized by x-ray diffraction, scanning electron microscope, transmission electron microscope and x-ray photoelectron spectroscopy. It was shown that the added tyrosine served both as a shape conductor for the formation of ZnO faceted nanorods and as a reducing agent of Ag(+) ions. In the reaction process, the complexation of Ag(+) with NH(3) and OH(-) decreased the redox potential of Ag(+)/Ag, which prevented the formation of isolated Ag nanoparticles in solution. The prepared Ag/ZnO nanocomposites showed potential applications in photodegradation of organic dye pollutants and destruction of bacteria.     

植物纤维增强PLA-EAA复合材料的制备与性能

开发新型环保材料以替代塑料已成为解决当前环境问题的主要途径,聚乳酸(PLA)虽然拥有良好的强度,而其较差的韧性极大地限制了其应用.针对此缺陷,本文以乙烯-丙烯酸共聚物(EAA)为增韧组分,蒸汽闪爆处理后的稻草纤维(SF)为增强组分加入PLA中,通过熔融挤出制备得到了不同原料配比的PLA/EAA/SF复合物,并通过对复合材料形态、热性能及力学性能的表征分析了EAA和植物纤维的加入及用量对复合材料性能的影响.研究结果表明:EAA用量的增加有效提高了复合物的韧性,但其强度低且抑制了聚乳酸的结晶进而使得复合物强度大幅降低;植物纤维的加入既体现明显的增强效果,又起到了连接两相作用,有利于EAA在PLA中的均匀分散,尤其是在高EAA含量的体系中,植物纤维加入还具有增韧效果;同时,EAA的加入还有利于改善复合材料的熔体流动性.当PLA/EAA/SF质量比为60/40/10时,复合材料冲击强度和断裂伸长率较纯PLA提高约15%和65%,且具有良好的力学性能及加工性.     

AuNRs@ZIF-8的制备及其表面增强拉曼散射光谱研究

表面增强拉曼光谱(Surface enhanced Raman spectroscopy, SERS)是一种分子光谱,具有快速、高灵敏和指纹识别的特性,在分析化学、生物医学等领域有着重要的应用。然而,在溶液样品中一些检测分子很难被SERS基底所吸附,导致分子拉曼信号增强困难。为此,本文提出了一种ZIF-8材料包覆金纳米棒(AuNRs)的核壳结构(AuNRs@ZIF-8)来实现拉曼信号增强,既可利用金纳米颗粒的表面等离激元增强特性,又可利用ZIF-8这种多孔MOFs材料的吸附性能,从而实现溶液样品的高灵敏拉曼检测。我们首先采用晶种法制备了均一性良好的AuNRs,然后对其进行聚乙烯吡咯烷酮(PVP)修饰,最后加入金属有机框架ZIF-8前驱体,得到AuNRs@ZIF-8核壳纳米结构。该结构对罗丹明(R6G)的SERS检测灵敏度很高,检测限可低至10⁻⁹ mol/L,并且线性关系和均一性均良好。此外,我们通过测试该结构吸收R6G前后的UV-Vis吸收光谱进一步证实了核壳纳米结构的生成和对目标分子的有效吸附。

     

表面疏水修饰增强改性硅藻土调湿性能及其对聚氨酯膜透湿性的影响

水性聚氨酯(PU)是一种环保绿色的涂层材料,广泛应用于皮革、纺织、建筑涂层等领域。作为皮革、纺织涂层时,聚氨酯的透湿性决定服装的穿着舒适性,而常规水性聚氨酯的透湿性较差,需要对其进行改性获得透湿性优异的涂层。本文采用CaCl₂和十七氟癸基三甲氧基硅烷(FAS-17)对硅藻土进行改性,研究了改性条件对硅藻土结构和性能的影响,将调湿性能较好的改性硅藻土(FAS-17-CaCl₂-D)与PU复合,研究复合膜的透湿性。结果表明：采用质量浓度为30wt%CaCl₂和0.8wt%FAS-17改性的硅藻土综合性能最好,改性后硅藻土的比表面积、孔隙结构增大,调湿性能提高,FAS-17表面疏水修饰进一步强化了其调湿作用。将性能最好的FAS-17-CaCl₂-D与PU复合后,FAS-17-CaCl₂-D/PU透湿性随着FAS-17-CaCl₂-D用量的增加先增大后减小,复合膜的疏水性提高。1%FAS-17-CaCl₂-D与PU复合制备的复合膜透湿率最大,...     

Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate

Solid dispersion systems have been widely used to enhance dissolution rate and oral bioavailability of poorly water-soluble drugs. However, the formulation process development and scale-up present a number of difficulties which has greatly limited their commercial applications. In this study, solid dispersions (SDs) of desloratadine (DSL) with povidone (PVP) and crospovidone (cPVP) were prepared by spray coating technique. The process involved the spray application of 96% ethanol solution of DSL and PVP/cPVP, and subsequent deposition of the coprecipitates onto microcrystalline cellulose pellets during drying by air flow in a mini spray coater. The results from the present study demonstrated that the spray coating process is efficient in preparing SDs with enhanced drug dissolution rate and it is highly efficient in organic solvent removal. Both PVP and cPVP greatly improved drug dissolution rate by SDs, with PVP showing better solubilization capability. Very fast drug dissolution rate is achieved from SDs containing PVP regardless of differences in K grade. SD with smaller particles of cPVP have higher drug dissolution rate in comparison to the cPVP with larger particles. Results from physical state characterization indicate that DSL in SDs exist in the amorphous (high free-energy) state which is probably stabilized by PVP/cPVP. After 6-month accelerated stability study, DSL remains amorphous, while PVP and cPVP act as anti-plasticizing agents, offering efficient steric hindrance for nucleation and crystal growth.     

Scalable preparation of alginate templated-layered double hydroxide mesoporous composites with enhanced surface areas and surface acidities

Layered double hydroxides (LDHs), also known as hydrotalcite-like layered clays, have previously been investigated as a potential solid alkaline catalyst. A necessary calcinations/rehydration procedure, however, is utilized to enhance surface area and catalytic activity of LDHs involved. Here we report on a scalable preparation of sodium alginate-templated MgAI-LDH (LDH/SA) mesoporous composites with high surface area and surface acidity. The powdery LDH/SA mesoporous composites are prepared using alginate as template by a scalable method of separate nucleation and aging steps (SNAS). Comparison with the pristine MgAl-LDH shows that the obtained LDH/SA composites exhibit the greatly enhanced surface area and surface activity of surface acid sites at the elevated high temperatures which have scarcely been reported previously. Our results may allow designing a variety of mesoporous LDH-containing composites with potential applications in specific catalysis and purification processes.