类脂囊泡包封药物顺铂的研究

用司盘(Span)系列非离子表面活性剂和胆固醇(CHOL)为主要膜材,通过薄膜-超声波法制备了顺铂囊泡,研究了影响包封率的主要因素,考察了顺铂囊泡在体外的释放性能.实验表明:在50℃超声50 m in的条件下,由Span20与CHOL(摩尔比为5∶3)制备的囊泡对0.60 g.L-1注射用顺铂包封率可达65%以上,且包封后的药物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。     

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。     

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.     

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.     

电场下离子型聚合物复合囊泡结构变化的分子动力学模拟

利用粗粒化分子动力学模拟研究了电场作用下离子型聚合物复合囊泡形变与破裂的过程.定量分析了囊泡破裂过程中的结构变化,包括囊泡的形变程度、破裂速度、组分分布以及破裂后的结构.研究表明,电场强度较弱时,囊泡表面所吸附的聚电解质首先脱落,囊泡由球形结构转变为椭球结构.随着电场强度增大,离聚物的离子侧基发生重新排布,囊泡表面电荷的有序结构被破坏,导致囊泡的结构无法维持而破裂,囊泡塌缩,分裂形成离聚物团簇,并进一步破裂为小尺寸的离聚物聚集体,均匀分散于溶液中.本文利用分子动力学模拟明确了电场中离子型高分子复合囊泡破裂过程的分子机理,为药物释放技术的优化及发展提供了理论支持.     

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。     

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.     

环糊精超分子体系囊泡的制备及其应用研究进展

环糊精(CD)是具有特殊的空腔、良好的稳定性并且可以区域选择性修饰的一类主体分子。近年来发现CD及其衍生物自组装形成的CD超分子体系——囊泡兼具囊泡和CD的生物模拟、分子识别和生物相容等优良特性。本文综述了CD及其衍生物囊泡的制备,同时还介绍了其在新型智能材料、药物输送和细胞模拟领域中的最新研究进展,并结合现阶段的研究状况,对该类囊泡体系的发展前景进行了展望。     

N,N-双十二烷基壳聚糖/胆固醇混合单分子膜及自组装囊泡性质

研究了添加胆固醇对N,N-双十二烷基壳聚糖(N,N-dilauryl chitosan, DLCS)单分子膜以及自组装囊泡性质的影响. 结果表明, 引入少量胆固醇会导致DLCS膜的凝聚性下降; 当胆固醇含量增加到一定程度后, 混合膜的凝聚性增强. 添加胆固醇可显著改变DLCS载药囊泡的药物释放行为, 少量胆固醇可以提高载药囊泡的释放速率和平衡药物释放百分率; 而较高含量胆固醇则可抑制囊泡的释放速率和降低平衡药物释放百分率. 此外, 囊泡平衡药物释放率与其单分子膜压缩模量呈现一定线性关系, 这说明胆固醇的引入导致囊泡分子膜凝聚性的改变, 从而改变囊泡的通透性. 通过调节胆固醇的加入量, 可以制得药物释放行为在一定范围内可控的自组装囊泡.     

Niosomes from alpha,omega-trioxyethylene-bis(sodium 2-dodecyloxy-propylenesulfonate): preparation and characterization

The synthesis and characterisation of new surfactants with peculiar physical-chemical properties are amongst the most promising and expanding issues in pharmacological colloid science. The most used vesicular carriers are liposomes prepared from a wide variety of natural and synthetic phospholipids, but several ionic and non-ionic amphiphiles have been used to form multilamellar and/or unilamellar vesicles. In the present study the synthesis of alpha,omega-trioxyethylene-bis(sodium 2-dodecyloxy-propylenesulfonate), an anionic Gemini surfactant, and its ability to form niosomes are elucidated. The compound forms vesicles with and without added cholesterol. The vesicular systems were characterized by size, shape and drug entrapment efficiency. The compounds to be incorporated are beta-carotene and ferulic acid, as antioxidants, acetyl salicylic acid, as FANS, and the antineoplastic 5-flurouracil, widely used in dermatological disorders. The results of this study show that alpha,omega-trioxyethylene-bis(sodium 2-dodecyloxy-propylenesulfonate) can be used for the preparation of niosomes entrapping lypophilic, amphiphilic or hydrophilic substances. These niosomes may be promising candidates as percutaneous carriers for the aforementioned drugs.     

Development,Characterization, and Evaluation of Liposomes and Niosomes of Bacitracin Zinc

The skin permeation of bacitracin zinc in liposomes and niosomes after topical application were elucidated in the present study with the to increase its penetration capacity and, hence, efficiency. The formulations of bacitracin zinc were prepared by film hydration method and characterized for vesicle shape, size, entrapment efficiency, and drug permeation across rat skin and also evaluated for their stability. Formulation with niosomes demonstrated a better skin permeation potential, sustained release characteristic, and higher stability as compared to liposomes. The ability of liposomes and niosomes to modulate drug delivery makes the two vesicles useful to formulate topical bacitracin zinc.     

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).     

吐温表面活性剂囊泡对姜黄素的包载作用

本文研究了烷基链不饱和度对吐温表面活性剂囊泡包载姜黄素的影响。相比吐温-80囊泡,吐温-60囊泡的包载使姜黄素表现出更大的紫外吸收和荧光发射强度、缔合常数和DPPH自由基清除能力。核磁共振氢谱结果表明姜黄素缔合于吐温-60囊泡双分子层中的亲水头基附近,而且姜黄素的酚羟基与吐温-60的酯基产生氢键作用。在吐温-80囊泡中,双键会使吐温-80烷基链产生弯曲或折叠,导致双分子层排列更加松散、极性更高。因此,姜黄素除了与吐温-80的酯基产生氢键作用外,还能与吐温-80烷基链尾部和中部的亚甲基发生作用。     

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   

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.     

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).     

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.     

Preparation and characterization of bolaform surfactant vesicles

Vesicular formulations (liposomes and niosomes) play an increasingly important role since they can be used as drug delivery and targeting systems. We described the formation of two niosomal systems based on synthetic bolaform surfactants (4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecanedioc acid diamide (BD-16) and alpha,omega-(4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecane (BC-16). Systems containing BD-16 or BC-16 and different amount of cholesterol (CH) were prepared by aqueous dispersion of films, followed by examination of methylene blue (MB) entrapment, particle size and morphology. Indeed, we also studied the hydration in the distilled water and physiological solution, in order to investigate the complexing ability on vesicle formation. The results obtained in this study show a high encapsulation capacity and this ability and the size depends on cholesterol content.