高压均质法制备载有维甲酸的纳米结构脂质载体

采用高压均质法制备了载有维甲酸(RA)的纳米结构脂质载体(Nanostructured Lipid Carriers, NLC),并用透射电镜(TEM)、粒度分析仪、 电位仪和高效液相色谱仪(HPLC)对其进行了表征. 结果表明,随高压均质循环次数的增加,NLC的均粒径从120 nm减小到10 nm,同时单分散性变差;NLC的微观形貌呈球形,表明其未结晶具有较好的载药能力;NLC将维甲酸浓度从20 g/mL(溶解于硅油)提高到56.26 g/mL,并能提高其光稳定性;NLC体系的稳定性良好, 电位高达( 30.9 0.6) mV,于4℃以10000 r/min冷冻离心120 min或避光保存6个月后粒径分布仍然基本不变,且可冷冻干燥( 40℃, 0.01 Pa)后长期保存.     

咪喹莫特纳米结构脂质载体的可控制备及表征

采用高压均质法制备咪喹莫特纳米结构脂质载体(IMQD-NLC),分别考察表面活性剂、高压均质操作参数及药物加入量对IMQD-NLC制备的影响,并对其形貌、物相、表面Zeta电位及体外释放特性等进行了表征. 结果表明,选取S-40和Span-20复配作为表面活性剂,随着S-40含量的增大,IMQD-NLC的平均粒径和Zeta电位的绝对值逐渐减小,而PI值呈现增大趋势;高的高压均质循环次数制备的IMQD-NLC平均粒径和PI值均比较低;药量增大,粒子平均粒径和PI值增大,而Zeta电位并没有发生明显变化;平均包封率为88.3%;IMQD-NLC呈无定型状态;IMQD-NLC在pH 1的释放介质中呈现先突释后缓释,而在pH 5.5的释放介质中呈现缓慢释放.     

New Peptide Functionalized Nanostructured Lipid Carriers with CNS Drugs and Evaluation Anti-proliferative Activity

Nanoparticulate systems have been widely investigated as delivery vectors for efficient drug delivery in different diseases. Nanostructured lipid carriers (NLC) are composed of both solid and liquid lipids (glyceryl dibehenate and diethylene glycol monoethyl ether) and have demonstrated enhanced biological compatibility and increased drug loading capability. Furthermore, the use of peptides, in particular cell-penetrating peptides, to functionalize nanoparticles and enhance cell membrane permeation was explored in this paper. In this paper, we described the synthesis of a new conjugated of tranylcypromine with MAP. In addition, taking into consideration our previous results, this study developed different NLCs loaded with three central nervous system (CNS) drugs (tacrine (TAC), rasagiline (RAS), and tranylcypromine (TCP)) functionalized with model amphipathic peptide (MAP) and evaluated their activity against cancer cells. Particle size analysis demonstrated NLC presented less than 200 nm and a polydispersity index less than 0.3. Moreover, in vitro results showed that conjugation of MAP with drugs led to a higher decrease in cell viability of a neuroblastoma cell line and Caco-2 cell line, more than MAP alone. Furthermore, NLC encapsulation contributed to higher cellular delivery and enhanced toxic activity at lower concentrations when compared with free or co-administration drug-MAP conjugate.     

Novel Nanostructured Lipid Carriers with Photoprotective Properties Made from Carnauba Wax,Beeswax, and Kenaf Seed Oil

This study was aimed to produce a stable kenaf seed oil-nanostructured lipid carrier (KSO-NLC) sunscreen, which can help in the photoprotective effect. The nanostructured lipid carrier (NLC) formulation was optimized and selected based on the results of mean particle size, polydispersity index (PDI), and storage stability of formulas at both chilled (4 ± 2 °C) and room (25 ± 2 °C) temperatures. Uvinul A plus B was added to KSO-NLC with the optimized formula (80% w/w aqueous phase, 20% w/w lipid phase, and 7% w/w of surfactants with a ratio of 70:15:15 of Tween 20: poloxamer 188: lecithin). The mean particle size distribution (224.73 ± 1.56 nm) and PDI (0.41 ± 0.01) of KSO-NLC were determined and were found to be stable against storage without creaming or phase separation. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging and 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical-scavenging activities of KSO-NLC were 5.43 ± 1.00 mg Trolox equiv. g⁻¹ of NLC and 6.70 ± 0.31 mg Trolox equiv. g⁻¹ of NLC, respectively. The Sun Protection Factor (SPF) of KSO-NLC, 41.38 ± 6.03 with a UVA/UVB ratio 0.64 ± 0.01, suggested a good photoprotective effect. The sustained release of Univul A plus B from KSO-NLC accompanied by its entrapment efficiency up to 64.09 ± 0.98% and drug loading (DL) of 32.05 ± 0.49% (maximum 50% DL capacity) proved that the degradation of the ultraviolet (UV) filter could be reduced. Therefore, the KSO-NLC sunscreen was a feasible solution for the photoprotective approach by using unconventional plant seed oil with a significant enhancement (P < 0.05) in many aspects compared to the formula without KSO incorporation.     

Characterization of Magnesium Orotate‐Loaded Chitosan Polymer Nanoparticles for a Drug Delivery System

The drug release properties of magnesium orotate (MgOr) encapsulated in the chitosan (CS) cavity and the complexation behavior between MgOr and CS were investigated. The MgOr‐loaded CS nanoparticles (MgOrCSNPs) were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, X‐ray diffraction, transmission electron microscopy, and scanning electron microscopy with energy‐dispersive X‐ray spectroscopy. MgOr was successfully encapsulated into the CS cavity. Results with 3‐(4,5‐dimethylthiazol‐2‐yl)2,5‐diphenyl tetrazolium bromide indicated that MgOrCSNPs retained their cytotoxic activity against the liver cancer cell line (HepG2) and breast cancer cell line (MCF‐7), and low toxicity against the human cell line (3T3) and human retinal epithelial cell line (ARPE‐19).     

Ballistic Modification of Nitramine Propellants with Special Reference to NG‐PE‐PCP‐Based High Energy Propellants

The burning rate pressure relationship is one of the important criteria in the selection of the propellant for particular applications. The pressure exponent (η) plays a significant role in the internal ballistics of rocket motors. Nitramines are known to produce lower burning rates and higher pressure exponent (η) values. Studies on the burning rate and combustion behavior of advanced high‐energy NG/PE‐PCP/AP/Al‐ and NG/PE‐PCP/HMX/AP/Al‐based solid rocket propellants processed by a conventional slurry cast route were carried out. The objective of present study was to understand the effectiveness of various ballistic modifiers viz. iron oxide, copper chromite, lead/copper oxides, and lead salts in combination with carbon black as a catalyst on the burning rate and pressure exponent of these high‐energy propellants. A 7–9 % increase in the burning rates and almost no effect in pressure exponent values of propellant compositions without nitramine were observed. However, in case of nitramine‐based propellants as compared to propellant compositions without nitramines, slight increases of the burning rates were observed. By incorporation of ballistic modifiers, the pressure exponents can be lowered. The changes in the calorimetric values of the formulations by addition of the catalysts were also studied.     

Formulation and Characterization of Novel Nanostructured Lipid Carriers with Photoprotective Properties Made from Carnauba Wax,Beeswax, Pumpkin Seed Oil,and UV Filters

Pumpkin seed oil (PSO) with carnauba wax and beeswax was used to develop nanostructured lipid carriers (NLC) loaded with a UV filter, Uvinul® A Plus B. The aims of the study were to optimize the concentration of PSO to develop a stable NLC formulation, determine storage stability of the NLC with and without PSO, and the synergistic effect of PSO-NLC with UV filter for photoprotective properties. The physical properties of NLC were optimized based on the mean particle size, polydispersity index, and storage stability. The optimized NLC consisted 10% lipid phase (3.5% carnauba wax, 3.5% beeswax, and 3.0% PSO) and 90% aqueous phase. After optimization, Uvinul® A Plus B was added in the optimized PSO-NLC to produce a photoprotective formulation. Uvinul® A Plus B consisted of both UVA (Diethylamino Hydroxybenzoyl Hexyl Benzoate) and UVB (Ethylhexyl Methoxycinnamate) filters. The NLC produced with PSO and Uvinul® A Plus B had mean particle size of 135 ± 2 nm and showed good physical stability under storage time. Besides that, the NLC produced also proven to have positive effect in enhancing the entrapment efficiency and drug loading, which were 82.86 ± 0.15% and 55.41 ± 0.04%, respectively, and showed sun protection factor value of 16.61 ± 3.45. The results indicated the presence of synergistic effect among the PSO-NLC with Uvinul® A Plus B.     

A Comparative Approach for the Preparation and Physicochemical Characterization of Lecithin Liposomes Using Chloroform and Non‐Halogenated Solvents

Organic solvents used in various pharmaceutical preparations may be associated with chronic health effects, with special emphasis on halogenated solvents. Liposomes, lipid bilayer membrane carriers, have potential applications in targeted drug delivery systems. The non‐halogenated solvents, acetonitrile and ethanol, were used in comparison to commonly used chloroform. The effect of solvents and dispersion medium was demonstrated using physicochemical properties, stability studies and hemolytic activity. Increased sonication time showed decreased particle size in phosphate buffer saline and water medium. Vesicles prepared from all solvents exhibited better stability in phosphate saline buffer than water when evaluated by particle size and zeta potentials. Liposomes showed a positive zeta potential in buffer solution whereas liposomes in water showed negative zeta potential. In vitro hemolytic activity of liposomes was done with fresh human red blood cells. Results in buffer solution were in the range of 1–4 % which further proved this medium superior to pure water. The findings of this study are helpful in suggesting the formulation of thin films by less hazardous solvents in terms of the environmental integrity and human health.     

Formulation and Characterization of Taxifolin‐Loaded Lipid Nanovesicles (Liposomes,Niosomes, and Transfersomes) for Beverage Fortification

In this study, nanovesicles such as transfersomes, niosomes, and liposomes prepared by an ethanol injection method (EIM) (EIM) and formulated with soybean lecithin, Tween 80, Span 60, and cholesterol, are used to improve the bioavailability of taxifolin, a natural antioxidant with beneficial properties for health and food preservation. Morphology, stability, and the in‐vitro release of the optimal formulations are fully examined. The obtained results indicate that taxifolin‐loaded nanovesicles present sizes ranging between 98 and 215 nm along with a narrow size distribution (polydispersity index less than 0.250). The zeta potential of nanovesicles is negative and in the range of ?20.40 to ?32.20 mV. The optimal formulations with the maximum encapsulation efficiency (72–75%) are the transfersomes formulated with lecithin and Tween 80 in the presence and absence of cholesterol. Additionally, in vitro release behavior of nanovesicles shows low taxifolin released (3.68–10.13%) at intestinal conditions, whereas more than 90% of taxifolin is released in gastrointestinal conditions. The compatibility between taxifolin and nanovesicles components is confirmed by FTIR. Transmission electron microscopy demonstrates spherical shaped particles around 200 nm. Backscattering profiles variations show the potential application of taxifolin nanovesicles for producing fortified apple juice with excellent physical stability. Practical Applications: Taxifolin is a flavanonol, which fulfills a particular task in preserving stable functions of the circulatory system owing to its special antioxidant ability and biological activity. Nevertheless, its low bioavailability is a salient drawback for biomedical and food applications. Thus, the current study is conducted to encapsulate taxifolin in nanovesicles (such as liposome, niosome, transfersome) by EIM to improve its bioavailability. Nanocarriers with relatively decent physical stability and high encapsulation efficiency can be brought about through Tween 80, soybean lecithin, and in the presence and absence of cholesterol as stabilizer which ensures the successful delivery of taxifolin to food formats such as beverages.     

Synthesis and Biological Evaluation of Indole‐2‐carbohydrazide Derivatives as Anticancer Agents with Anti‐angiogenic and Antiproliferative Activities

A novel series of indole‐2‐carbohydrazide derivatives were synthesized, characterized, and evaluated for their antiproliferative activities against two cancer cell lines, HCT116 and SW480, and a normal human fetal lung fibroblast cell line, MRC‐5. Among this series, compound 24 f displayed potent cytotoxic activities in vitro against HCT116 and SW480 cell lines with GI₅₀ values of 8.1 and 7.9 μm , respectively, and was inactive against MRC‐5 cells. The newly synthesized compounds were also evaluated for anti‐angiogenesis capabilities by chick chorioallantoic membrane, human umbilical vein endothelial cell (HUVEC) migration, and endothelial microtubule formation assays. Moreover, the effects of 24 f on the vascular endothelial growth factor receptor‐2 and the signaling pathway in HUVECs indicated that this compound inhibits VEGFR‐2 and its downstream related proteins. These results indicate that compound 24 f , as well as the other derivatives, are promising inhibitors of angiogenesis.     

Water‐Triggered Rapid Release of Biocide with Enhanced Antimicrobial Activity in Biodiesel

Biodiesel inherently contains more water than mineral diesel and as a result microbial contamination is a major problem that hinders its widespread application. The current method of removing the microbial contamination is direct addition of biocide. However, this method cannot enrich the water phase with biocide rapidly enough, leading to unavoidable overdosing of biocide and environmental issues. Here, biocide is encapsulated within hydrogel microparticles with a water‐triggered release feature to improve antimicrobial efficiency of biocide in biodiesel. To demonstrate the water‐triggered release mechanism, a green dye is encapsulated within the microparticles. The encapsulated dye remains inside the microparticles for more than 6 weeks when the microparticles are stored in oil phase; however, the dye releases in 4 min when the microparticles contact water. Using this water‐triggered release strategy, biocide is successfully delivered to the water phase in biodiesel. The encapsulated biocide shows higher antimicrobial efficacy than that of free biocide, in both short‐term and long‐term experiments. The possibility of scaling up the production of hydrogel microparticles using bulk emulsification method is also explored. Moreover, the water‐triggered release strategy can be used for releasing other water‐soluble functional materials. This opens opportunities for a wide range of encapsulation and controlled delivery applications.     

Copolymers of acrylic acid with N‐vinylpyrrolidinone and 2‐hydroxyethyl methacrylate as pH‐responsive hydrogels synthesized through a photoinitiator‐free photopolymerization technique

pH‐sensitive hydrogels for biomedical applications were synthesized using a photoinitiator‐free technique involving the initiation of photopolymerization by donor/acceptor pairs. The differential photocalorimetric technique indicated a high polymerization rate for the N‐vinylpyrrolidinone (NVP, donor)/acrylic acid (AA, acceptor) pair at a 1:1 molar ratio. However, photopolymerization of larger quantities of these monomers (1:1 molar ratio) produced a water‐soluble polymer. Nevertheless, an anionic hydrogel was successfully formed when a small quantity of 2‐hydroxyethyl methacrylate (HEMA) was included in the NVP/AA formulation. A mixture of HEMA and AA, although both are classified as acceptors, photopolymerized to produce a copolymer which functioned as an anionic hydrogel. The swelling and drug release of these hydrogels were investigated in acidic, neutral and basic pH environments. Their biocompatibility with HaCaT human epidermal keratinocyte cells was tested and a positive cell growth as evidenced by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide (MTT) cell proliferation assay indicated that these hydrogels have no toxic effect on HaCaT. Copyright © 2006 Society of Chemical Industry     

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

The present study describes the synthesis and anticancer activity of novel octahedral Pt^IV complexes with cyclohexyl functionalized ethylenediamine‐N,N′‐diacetate‐type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s‐cis is the preferred geometry of these Pt^IV complexes with tetradentate‐coordinated (S,S)‐ethylenediamine‐N,N′‐di‐2‐(3‐cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell‐cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt^IV complexes against various cancer cell lines (IC₅₀ range: 1.9–8.7 μM ) was higher than that of cisplatin (IC₅₀ range: 10.9–67.0 μM ) and proceeded through completely different mechanisms. Cisplatin induced caspase‐dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt^IV complexes caused rapid, caspase‐independent, oxidative stress‐mediated non‐apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.     

Transfer, Perception, and Activity of Male Pheromone of Acrolepiopsis assectella with Special Reference to Conspecific Male Sexual Inhibition

In the leek moth, Acrolepiopsis assectella, the male, stimulated by a calling female, produces a sexual pheromone that is active on the female. The male-produced pheromone blend contains eight alkanes previously isolated from the male hair-pencils. We used EAG techniques to study the effect of the pheromone on females reared on leek or on artificial diet and on males reared on leek. The optimal stimulation duration appeared to be 1.6 sec exposure to the pheromone or components. The concentrations tested on the antenna were of the order of 10¹² molecules/cm³. The hair-pencil extract tested was of an estimated concentration of around 10⁹ molecules/cm³. The antennal responses are expressed relative to responses to a standard, amyl acetate, but also as an absolute value. Generally, females reared on artificial diet and males reared on leek responded better than females reared on leek. Of the alkanes tested, those present in hair-pencils gave higher responses, with hexadecane always giving the strongest response. A possible inhibiting activity of male leek moth pheromone on the sexual behavior of conspecific males was investigated. The behavior of sexually stimulated males was observed in the presence of other males, hair-pencil extracts, and different compounds either pure or in a mixture. The experiments established that in this species, male pheromone inhibits wing fluttering duration of conspecific males. This inhibition was obtained not only with fluttering males as a source of pheromone but also with all the alkanes tested. The inhibition was due to hair-pencil chemicals, particularly if these were perceived by olfaction plus contact. Wing fluttering increased the inhibitory activity of male-derived alkanes.     

A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η5-C5Me4R} Complexes with Variable R Groups

Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η⁵-C₅Me₄R)Cl(μ-Cl)]₂ (R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C₆H₄F, 1d; R = 4-C₆H₄OH, 1e), their 2-phenylpyridyl mononuclear derivatives [Ir(η⁵-C₅Me₄R)(k_N,k_CPhPy)Cl] (2a–d), and the dimethylsulfoxide complex [Ir{η⁵-C₅Me₄(4-C₆H₄OH)}Cl₂(κ_S-Me₂S=O)] (3) were synthesized, structurally characterized, and assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5). Complexes 2b (R = H) and 2d (4-C₆H₄F) emerged as the most active ones and were selected for further investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumoricidal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.     

A Wavelet Characterization of Continuous‐Time Periodically Correlated Processes with Application to Simulation

We introduce a wavelet characterization of continuous‐time periodically correlated processes based on a linear combination of infinite‐dimensional stationary processes. The finite version of this linear combination converges to the main process. The first‐order and second‐order estimators based on the wavelets are presented. Under a simple and easy algorithm, the periodically correlated process is simulated for a given autocovariance function. The proposed algorithm has two main advantages: first, it is fast, and second, it is distribution free. We indicate through four examples that the simulated data are periodically correlated with the desired period.