类脂囊泡作为头孢噻肟钠药物载体的研究

用司盘(Span)系列非离子表面活性剂和胆固醇(CHOL)通过真空旋转一超声波法制备了头孢噻肟钠囊泡,研究了包封条件对包封率的影响及包封后的药物在体外的模拟释放,考察了头孢噻肟钠囊泡的形态和构造。实验表明:Span20与CHOL摩尔比为2∶1,50°C超声30m in,对1.00g/L的注射用头孢噻肟钠的包封率可达55%以上,而且在模拟肠流体和模拟胃流体中均有缓释作用。     

非离子表面活性剂囊泡对头孢菌素药物的缓释作用

用超声法制备了Span系列非离子表面活性剂囊泡,研究了它们对几种水溶性头孢菌素药物的包封作用及影响包封率的因素,通过透射电镜对囊泡的形态和大小进行了鉴定.实验表明,制得的囊泡多为球形单室囊泡,且包封后的药物在模拟肠液和模拟胃液中均有缓释作用.     

类脂囊泡作为5-氟尿嘧啶药物载体的研究

采用薄膜分散法,以司盘类非离子表面活性剂和胆固醇为主要原料,制备抗肿瘤药物5-氟尿嘧啶(5-FU)类脂囊泡.以包封率为考察指标,对可能影响包封的各种实验条件进行优化.实验表明:药物浓度为1.0 g/L,Span 20与胆固醇比例为4∶3,50℃超声30min,所制得的5-FU类脂囊泡的包封率可达40%以上.透射电镜照片显示所制得的类脂囊泡为球形单室结构,测得平均粒径为393nm,且分布较均匀,表明制得的囊泡粒径符合注射给药的要求.     

失水山梨醇脂肪酸酯-聚乙二醇嫁接的聚乙烯醇化磁性药物载体的制备及应用

通过丁二酸酐将失水山梨醇脂肪酸酯(Span80)和聚乙二醇(PEG400)联接在一起,合成了一种新的非离子表面活性剂.然后将其嫁接在聚乙烯醇(PVA)化的Fe3O4磁性粒子上,合成了一种新型靶向药物载体.这种载体兼备了Span80/PEG400类脂囊泡和磁性材料的特点,具有良好的稳定性和靶向作用.将这种新型载体用于两性霉素的包封,包封率可达96.6%,且方法简便.实验过程中采用了FTIR, NMR, XRD和TEM等多种手段进行表征.     

非离子表面活性剂囊泡包封药物头孢唑啉钠的研究

实验通过超声波法制备了吐温类非离子表面活性剂囊泡，研究了它们对药物质奖励不孢唑啉钠（CEZ）的包封作用以及被包封的CEZ在模拟胃液及模拟肠液中的释放情况。实验表明，吐温40与胆固醇体积比为1：1时形成的非离子表面活性剂囊泡对1mg/mL的CEZ的包封率是20％，而且在模拟胃液和模拟肠液中，对包封的药物都有一定的缓释作用，因此有可能作为临床上的药物缓释剂。     

赖氨酸在甘草次酸弹性囊泡形成过程中的作用机制

制备和评价含赖氨酸的甘草次酸弹性囊泡, 并考察赖氨酸在囊泡形成过程中的作用机制. 在水合介质中加入赖氨酸, 利用薄膜-高压均质法制备甘草次酸弹性囊泡. 并合成了甘草次酸赖氨酸盐及其弹性囊泡作为对比制剂. 通过对粒径、zeta电位、包封率、相转变温度、变形性和体外经皮渗透性的测试, 考察赖氨酸在甘草次酸弹性囊泡中的存在形式及作用. 结果显示加入赖氨酸后, 甘草次酸弹性囊泡的粒径略有降低, 膜相转变温度降低, 包封率和囊泡变形性显著提高, 载药量提高近30倍(1.5 mg·mL-1), 并显著高于其赖氨酸盐所形成囊泡的载药量和弹性. 此外, 赖氨酸的加入使弹性囊泡的变形能力增加, 8 h累积透过量和皮肤驻留量分别提高4.3倍和9.2倍. 表明赖氨酸与甘草次酸形成离子缔合物, 促进甘草次酸参与膜的形成, 使膜的流动性增加, 赖氨酸与弹性囊泡对提高囊泡载药量起协同作用.     

顺铂温敏载药粒子的制备表征

制备了顺铂温敏载药纳米粒子，表征其相关性质并考察不同温度下对体外肿瘤细胞的生长抑制作用。制备的两亲嵌段聚合物在水溶液中自发形成胶束结构并包裹顺铂，测定顺铂载药粒子的结构、形态、粒径及包封率、载药量、晶体状态等特性，并对顺铂的体外释放以及不同细胞系体外毒性也做了研究。载药粒子粒径为83.3 ± 4.3 nm，载药量为37.8%，包封率为77.8%。血清中相变温度39.3 ℃。载药颗粒在单纯化疗时细胞抑制率较小，加热后抑制作用明显增加(P<0.01)，与游离药物相近(P>0.5)。顺铂载药纳米粒子具有较好的温控特性，为顺铂在肿瘤热靶向治疗中的应用提供了一条新的途径。     

超临界CO2法制备头孢唑啉钠脂质体

采用超临界CO2(scCO2)流体代替有机溶剂一步法制备了头孢唑啉钠药物载体脂质体. 研究了该脂质体的尺寸、稳定性和药物的包封率. 结果表明, 脂质体的尺寸和稳定性依赖于制备压力, 脂质体对头孢唑啉钠的包封率与乙醇和脂浓度有关, 采用超临界CO2法制备脂质体的药物包封率比采用薄膜分散法(Bangham method)制备的包封率高.     

离子键交联聚合物囊泡的制备及对药物的负载与释放

通过双亲性接枝共聚物海藻酸钠接枝聚N-异丙基丙烯酰胺(SA-g-PNIPAM)与Ca2+之间的静电作用,在水溶液中制备了温度敏感性离子键交联聚合物囊泡,并以5-氟尿嘧啶(5-FU)为模型药物,研究了聚合物囊泡对5-FU的负载与释放性能。该囊泡疏水性的膜由海藻酸钠与Ca2+之间的静电作用复合形成。透射电镜研究表明,囊泡具有空心结构,直径在100~150nm左右。聚合物囊泡的最低临界溶解温度(LCST)为34.5℃左右。聚合物囊泡对5-FU具有较高的载药量和包封率,其药物释放速率随溶液p H值的增加而降低,随离子强度的增大而增大,表现出良好的环境响应性。     

血红蛋白在Span 80/PEG 400/H2O囊泡体系中的结构性质

通过紫外-可见吸收光谱、荧光光谱、动态光散射、圆二色谱、负染-透射电镜(NS-TEM)和冷冻蚀刻-透射电镜(FE-TEM)等实验方法研究了血红蛋白(Hb)与Span 80/PEG 400/H₂O囊泡间的相互作用及其结构特性. 结果表明: Hb易于吸附在囊泡表面, 使得囊泡的表观半径稍有增大; Hb的肽链在囊泡表面能够逐渐伸开, 特征荧光峰强度显著增强, 部分氨基酸残基进一步暴露, α-螺旋结构含量减少, β-折叠和β-转角结构含量增加, 无规卷曲结构含量基本不变. 囊泡体系中Hb的稳定性与囊泡的稳定性有关.     

Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol

Monomers of some amphiphiles organize into bilayers to form liposomes and niosomes. Such bilayers are unstable or leaky and hence cholesterol is a common ingredient included to stabilize them. Cholesterol stabilizes bilayers, prevents leakiness, and retards permeation of solutes enclosed in the aqueous core of these vesicles. Other than cholesterol a material with good bilayer-stabilizing properties is yet to be identified. We have substituted cholesterol with fatty alcohols in niosomes containing polyglyceryl-3-di-isostearate (PGDS) and polysorbate-80 (PS-80) to explore their membrane-stabilizing property via permeation studies. Niosomes of polyglyceryl-3-di-isostearate, fatty alcohol/cholesterol, and polysorbate were prepared by ether injection method. Aqueous solution of ketorolac tromethamine (KT) was entrapped in them. The effects of alkyl chain length of fatty alcohols (C(12), C(14), C(16), C(18), and C(16+18)), of acyl chain length of polyoxyethylene sorbitan monoester surfactants, and of the molar ratio of lipid mixture on the release rate of ketorolac from niosomes were assessed by employing modified dissolution-dialysis method. Niosomes with cholesterol or fatty alcohols have exhibited a common release pattern. Niosomes containing fatty alcohol showed a considerably slower release rate of KT than those containing cholesterol. Based on the release rate, fatty alcohols can be ranked as stearyl相似文献   

Nonionic Surfactant Vesicles as a Carrier for Transdermal Delivery of Frusemide

The aim of the present study was to formulate and evaluate the nonionic surfactant vesicles of frusemide in order to enhance its skin permeation. The process variables which could affect the preparation and properties of the niosome formulation studied included type of spans, ratio of span and cholesterol, ratio of cholesterol and dicetylphosphate (DCP), concentration of drug, type of solvent, hydration media and time of hydration. The formulated niosomes thus were characterized for various parameters such as surface morphology, size, entrapment efficiency, skin permeation, etc. Stability of the niosomes in terms of drug holding capacity was assessed for a period of 30 days on storage under defined conditions. The maximum entrapment efficiency of 77.73±2.36% was obtained with niosomes formulated from Span 60∶Cholesterol∶DCP (47.5∶47.5∶5) using chloroform:methanol (4∶1) as the solvent system at the hydration time of 1 hr. A direct relationship was observed between the percentage leaching of the drug out of the vesicles and temperature. Higher transdermal flux was obtained with niosomal gel (9.2±0.5 μg/cm²/hour) in comparison to conventional gel (6.4±0.3 μg/cm²/hour).     

Fluorescence and dynamic light scattering studies of niosomes-membrane mimetic systems

Niosomal vesicles are more stable than liposomal vesicles due to higher chemical stability of surfactants compared to phospholipids. Niosomes have been prepared from Span20, Span80, Tween20 and Tween80. Fluorescence resonance energy transfer studies have been performed in these systems to determine donor-acceptor distances. It has been found that the fluorescence resonance energy transfer efficiency is better in niosomes compared to micelles. The formation of niosomes is guided by the hydrophile-lipophile balance value of the nonionic surfactant.     

Novel method for obtaining homogeneous giant vesicles from a monodisperse water-in-oil emulsion prepared with a microfluidic device

A novel technique called the "lipid-coated ice droplet hydration method" is presented for the preparation of giant vesicles with a controlled size between 4 and 20 microm and entrapment yields for water-soluble molecules of up to about 30%. The method consists of three main steps. In the first step, a monodisperse water-in-oil emulsion with a predetermined average droplet diameter between 4 and 20 microm is prepared by microchannel emulsification, using sorbitan monooleate (Span 80) and stearylamine as emulsifiers and hexane as oil. In the second step, the water droplets of the emulsion are frozen and separated from the supernatant hexane solution by precipitation, followed by a removal of the supernatant and followed by the replacement of Span 80 by using a hexane solution containing egg yolk phosphatidylcholine, cholesterol, and stearylamine (5:5:1, molar ratio). This procedure is performed at -10 degrees C to keep the water droplets of the emulsion in a frozen state and thereby to avoid extensive water droplet coalescence. In the third step, hexane is evaporated at -4 to -7 degrees C and an external water phase is added to the remaining mixture of lipids and water droplets to form giant vesicles that have an average size in the range of that of the initial emulsion droplets (4-20 microm). The entrapment yield and the lamellarity of the vesicles obtained depend on the lipid/water droplet ratio and on the composition of the external water phase. At high lipid/water droplet ratio, the giant vesicles have a thicker membrane (indicating multilamellarity) and a higher entrapment yield than in the case of a low lipid/water droplet ratio. The highest entrapment yield ( approximately 35%) is obtained if the added external water phase contains preformed unilamellar egg phosphatidylcholine vesicles with an average diameter of 50 nm. The addition of these small vesicles minimizes the water droplet coalescence during the third step of the vesicle preparation, thereby decreasing the extent of release of water-soluble molecules originally present in the water droplets. The GVs prepared can be extruded through polycarbonate membranes to yield large unilamellar vesicles with about 100 nm diameter. This size reduction, however, leads to a decrease in the entrapment yield to about 12% due to solute leakage from the vesicles during the extrusion process.     

Solid lipid nanoparticles prepared by solvent diffusion method in a nanoreactor system

In this study, water-in-oil (W/O) miniemulsion was used as nanoreactor to prepare solid lipid nanoparticles (SLN) by solvent diffusion method. n-Hexane, Tween 80 and Span 80 were used as the oil phase and surfactant combination for preparation of W/O miniemulsion, respectively. The stable miniemulsion with the particle size of 27.1 ± 7.6 nm was obtained when the composition of water/Tween 80/Span 80/n-hexane was 1 ml/18 mg/200 mg/10 ml. Clobetasol propionate (CP) was used as a model drug. The physicochemical properties of the SLN, such as particle size, zeta potential, surface morphology, drug entrapment efficiency, drug loading capacity and in vitro drug release behaviors were investigated, comparing with those of SLN prepared by conventional aqueoethod. The SLN prepared by the novel method displayed smaller particles size and higher dus solvent diffusion mrug entrapment efficiency than those of SLN prepared by the conventional method. The drug entrapment efficiency decreased with increasing of charged amount of drug, and 15.9% of drug loading was achieved as the charged amount of drug was 20%. The in vitro drug release tests indicated that the drug release rate was faster than that of SLN prepared by the conventional method, and the drug content in SLN did not affect the in vitro drug release profile.     

A new crown ether as vesicular carrier for 5-fluoruracil: synthesis, characterization and drug delivery evaluation

Niosomes have shown promise as cheap and chemically stable drug delivery systems. In this paper a novel crown ether amphiphile, 1,16-hexadecanoyl-bis-(2-aminomethyl)-18-crown-6 (Bola A-16), has been synthesized with the aim of developing a long time stable controlled release system. Niosomes have been prepared with different molar ratios of amphiphile and cholesterol and their morphological properties have been determined by quasi-elastic light scattering and transmission electron microscopy. The composition of niosomes affects the entrapment efficiency and the release rate of 5-fluorouracil, a well-known antineoplastic molecule. In addition, other two known azacrown ether amphiphiles (4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecanedioc acid diamide (Bola D-16) and ,ω-(4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecane (Bola C-16), have been synthesized and the obtained vesicles have been characterized for comparison. Furthermore, the release profile of 5-fluorouracil in vitro, from these niosomes, has been studied over a period of 6 h in order to simulate a hematic adsorption.     

Synthesis of gold nanoparticles in niosomes

This work outlines a novel method for the synthesis of stable gold nanoparticles within the spatially confined region of vesicles. For the first time, Span/cholesterol based niosomes have been used for nanoparticle synthesis. The restricted geometry within niosomes prevents nanoparticle aggregation. The results have important implications for controlled delivery of nanoparticles for therapeutic applications.     

Evaluation of compatibility of itraconazole with excipients used to develop vesicular colloidal carriers

Liposomes and niosomes are known to be efficient vehicles for localized and systemic delivery of particularly lipophilic drugs resulting in their improved bioavailability, targeted delivery, and fewer side effects. These systems consist of bilayered membrane structures comprising amphiphilic molecules like phosphatidylcholine (liposomes) and nonionic surfactants (niosomes). Itraconazole (ITZ) is a widely used insoluble antifungal agent, which is known to be poorly absorbed from available marketed dosage forms. For countering the bioavailability related problem of oral ITZ products, vesicular systems like liposomes and niosomes could provide a rational approach. Drug–excipient interaction is being considered as an essential first step in development of any drug delivery system nowadays. Therefore, the present work describes the evaluation of drug–excipient interactions of ITZ with selected excipients used for development of liposomes and niosomes. Analytical techniques like differential scanning calorimetry, Fourier transform infrared spectroscopy, optical microcopy, and X-ray powder diffraction analysis were utilized for assessing the drug–excipient interactions. Isothermal stress testing was also performed to quantitatively measure the percent change in initial drug content from ITZ–excipient blends kept under stress conditions. The excipients included phospholipids (Phospholipon 90G^®, Phospholipon 90H^®), surfactants (Span 40 and Span 60), vesicular membrane stabilizer (cholesterol), and a solubilizer (3-hydroxypropyl-betacyclodextrin).     

Quantitative investigation, stability and in vitro release studies of anti-TB drugs in Triton niosomes

The highly stable innocuous niosomes composed of four components (Triton X 100, polyethylene glycol 2000, water, Span 80) have been prepared successfully and characterized using particle size analyzer, transmission and scanning electron microscopy. The mean size has been found to be in the range 200-300 nm. The optimization of niosomes has been carried out using fluorescence spectroscopy. An attempt has been made to incorporate anti-tuberculosis drugs (ATD's) in the prepared niosomes. The stability and encapsulation efficiency of these drugs in the niosome have also been assessed and high encapsulation efficiency is observed. Such high encapsulation efficiency will serve as an advantage to solve the problem of multi-drug resistance in case of tuberculosis. Release studies and kinetics have been carried out to investigate the release behavior of drugs from the prepared niosomes. Fickian or diffusional release has been observed for rifampicin and isoniazid and a non-Fickian release mechanism for pyrazinamide. Fluorescence probe quenching technique has been used to determine the location and distribution coefficient of the ATD's in niosome/water system.