共轭亚油酸与海藻酸钠囊泡化自组装纳米容器及其药物缓释性能

脂肪酸囊泡(FAV)是一类重要的纳米容器,然而其形成pH范围较窄且偏碱性环境,限制了其应用。 本文将共轭亚油酸(CLA)与海藻酸钠(SA)在近中性环境下共同自组装囊泡化纳米容器并提高其膜稳定性。动态激光光散射(DLS)和透射电子显微镜(TEM)结果表明,当SA质量分数为25%~50%时复合体系可在近中性条件下自组装形成50~250 nm尺寸的囊泡化纳米容器,且pH=7.4时随着质量分数增加囊泡化纳米容器直径增大。 根据SA和CLA在中性环境的物种存在形式推测,二者通过氢键作用驱动形成囊泡化纳米容器。 体外模拟释放实验表明,囊泡化纳米容器具有较高包覆率和较优缓释效果,有望应用于药物传输领域。     

Fatty alcohols or fatty acids as niosomal hybrid carrier: effect on vesicle size, encapsulation efficiency and in vitro dye release

Niosomal hybrid mixtures are prepared with bilayer stabilizer cholesterol from non-ionic surfactants span 20 (HLB value 8.6), span 60 (HLB 4.7) and span 85 (HLB 1.8) in presence of dicetyl phosphate (DCP) where fatty acids or fatty alcohols (C14, C16 and C18) are used as carrier. Hybrid mixtures upon hydration with aqueous phosphate buffer (pH 7.4) spontaneously produce vesicular phase which can encapsulate 5(6)-carboxyfluorescein (CF). Effect of fatty alcohols and fatty acids on the vesicle size has been studied by dynamic light scattering (DLS), freeze-fracture scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Release rates of CF from vesicular suspensions are found to be dependent on carriers as well as surfactants used. Fatty acid coated hybrids form large multilamellar vesicles (LMV) (size range 10-15 microm) where as fatty alcohol coated hybrid systems form small multilamellar vesicles (SMV) with an average diameter of 400 nm, in all cases vesicles are polydisperse (PI approximately 0.9) in nature.     

Niosomes from 80s to present: The state of the art

Efficient and safe drug delivery has always been a challenge in medicine. The use of nanotechnology, such as the development of nanocarriers for drug delivery, has received great attention owing to the potential that nanocarriers can theoretically act as “magic bullets” and selectively target affected organs and cells while sparing normal tissues. During the last decades the formulation of surfactant vesicles, as a tool to improve drug delivery, brought an ever increasing interest among the scientists working in the area of drug delivery systems. Niosomes are self assembled vesicular nanocarriers obtained by hydration of synthetic surfactants and appropriate amounts of cholesterol or other amphiphilic molecules. Just like liposomes, niosomes can be unilamellar or multilamellar, are suitable as carriers of both hydrophilic and lipophilic drugs and are able to deliver drugs to the target site. Furthermore, niosomal vesicles, that are usually non-toxic, require less production costs and are stable over a longer period of time in different conditions, so overcoming some drawbacks of liposomes.     

Silicone nanocapsules templated inside the membranes of catanionic vesicles

A simple and effective way to synthesize hollow silicone resin particles of controlled diameter is presented. The synthesis utilizes catanionic vesicles as templates for the polycondensation/polymerization processes of 1,3,5,7-tetramethylcyclotetrasiloxane (D4H) within their membranes. Two different surfactant systems were used to form the vesicular templates: mixtures of dodecyltrimethylammonium bromide (DTAB) and sodium dodecylbenzenesulfonate (SDBS) in the cationic (the DTAB/SDBS system) or anionic (the SDBS/DTAB system) rich region of the phase diagram. The templates obtained from these surfactant mixtures form spontaneously unilamellar vesicles in aqueous solution. The vesicular templates swell upon addition of D4H, thus increasing their size. The silicone resin was obtained in acid- or base-catalyzed polycondensation and ring-opening polymerization processes of D4H. In the case of the DTAB/SDBS system the formation of a densely cross-linked silicone material with SiO3/2 units allowed the nanocapsules to retain the vesicular shape after removal of the template, whereas in the SDBS/DTAB system, the polymer produces capsules which are too smooth to support surfactant lysis. The morphology of the silicone nanocapsules was analyzed using transmission electron microscopy (TEM) and, in some cases, atomic force microscopy (AFM). TEM and AFM reveal discrete hollow particles with a small amount of linked or aggregated hollow silica shells.     

Characterization and Aggregation Behaviors of Mixed DDAB/SDS Solution With and Without Poly(4-styrenesulfonic Acid-Co-Maleic Acid) Sodium

Synthetic vesicles are formed by cationic and anionic surfactants, didodecyldimethylammonium bromide (DDAB), and sodium dodecylsulfate (SDS). The morphology, size, and aqueous properties of cationic/anionic mixtures are investigated at various molar ratios between cationic and anionic surfactants. The charged vesicular dispersions made of DDAB/SDS are contacted or mixed with negatively charged polyelectrolyte, poly(4-styrenesulfonic acid-co-maleic acid) sodium (PSSAMA), to form complexes. Depending on DDAB/SDS molar ratio or PSSAMA/vesicle charge ratio, complexes flocculation or precipitation occur. Characterization of the cationic/anionic vesicles or complexes formed by the catanionic vesicles and polyelectrolytes is performed by transmission electron microscope (TEM), dynamic light scattering (DLS), conductivity, turbidity, and zeta potential measurements. The size, stability, and the surface charge on the mixed cationic/anionic vesicles or complexes are determined.     

Investigation on the aggregation behaviors of DDAB/NaDEHP catanionic vesicles in the absence and presence of a negatively charged polyelectrolyte

The aggregation behaviors of the cationic and anionic (catanionic) surfactant vesicles formed by didodecyldimethylammonium bromide (DDAB)/sodium bis(2-ethylhexyl) phosphate (NaDEHP) in the absence and presence of a negatively charged polyelectrolyte are investigated. The amount of the charge on the vesicle can be tuned by controlling the DDAB/NaDEHP surfactant molar ratio. The charged vesicular dispersions made of DDAB/NaDEHP are mixed with a negatively charged polyelectrolyte, poly(4-styrenesulfonic acid-co-maleic acid) sodium (PSSAMA), to form complexes. Depending on the polyelectrolyte/vesicle charge ratio, complex flocculation or precipitation occurs. Characterization of the catanionic vesicles and the complexes are performed by transmission electron microscope (TEM), Cryo-TEM, dynamic light scattering (DLS), conductivity, turbidity, zeta potential, isothermal titration calorimetry (ITC) and small-angle X-ray scattering (SAXS) measurements.     

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.     

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   

可聚合囊泡体系(烯丙基-二甲基-十二烷基溴化胺和十二烷基硫酸钠)在溶液中的盐效应

高稳定的囊泡广泛用于制作生物模型、药物输送以及合成纳米材料的模板。获得高稳定囊泡结构的重要方法之一是用聚合反应固定囊泡结构。作为可聚合囊泡制备的前期基础工作,研究了一种可聚合的囊泡体系：1-丙烯基－2,2,二甲基－十二烷基溴化胺（ADDB）和ADDB与十二烷基磺酸钠（SDS）的等摩尔比混合体系。该囊泡体系即使在高浓度盐水中也能够自发地形成均相的囊泡溶液。在聚合之前,采用动态激光光散射（DLS）、冷冻蚀刻透射电镜（FF-TEM）技术研究了可聚合囊泡的盐效应。DLS测试发现没有盐存在时,囊泡大小为83 nm,盐的浓度增加到250 mmol/L时,囊泡尺寸增大到250 nm。然而继续增大盐浓度到1000 mmol/L, 囊泡尺寸减小到180nm. FF-TEM结果发现盐浓度小于150 mM时, 单个囊泡为70 nm左右,然而明显存在囊泡的絮凝与融合;当盐浓度增加到400 mM时,单个囊泡尺寸减小到20 nm. 因此DLS 观测到囊泡尺寸增大的原因是由于囊泡的絮凝与融合;而尺寸减小的原因是由于在高盐浓度下,盐屏蔽了带电颗粒之间的静电相互作用,在熵增的驱使下,大囊泡变成小囊泡。     

Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study

As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics.     

Plasmonic vesicles of amphiphilic gold nanocrystals: self-assembly and external-stimuli-triggered destruction

We have developed a new class of plasmonic vesicular nanostructures assembled from amphiphilic gold nanocrystals with mixed polymer brush coatings. One major finding is that the integration of gold nanocrystals (nanoparticles and nanorods) with two types of chemically distinct polymer grafts, which are analogous to block copolymers as a whole, creates a new type of hybrid building block inheriting the amphiphilicity-driven self-assembly of block copolymers to form vesicular structures and the plasmonic properties of the nanocrystals. In contrast to other vesicular structures, the disruption of the plasmonic vesicles can be triggered by stimulus mechanisms inherent to either the polymer or the nanocrystal. Recent advances in nanocrystal synthesis and controlled surface-initiated polymerization have opened a wealth of possibilities for expanding this concept to other types of nanocrystals and integrating different types of nanocrystals into multifunctional vesicles. The development of multifunctional vesicles containing stimuli-responsive polymers could enable their broader applications in biosensing, multimodality imaging, and theragnostic nanomedicine.     

空心纳米磷酸钙载药体系的制备与表征

非离子表面活性剂Tween 80和PEG 6000在水溶液中以一定的比例混合可形成稳定的类磷脂囊泡结构,这些囊泡可以作为模板来合成磷酸钙纳米空球颗粒。所制备的磷酸钙材料的结构和形貌通过TEM,SEM,FTIR,XRD进行了表征,是尺寸为100～150 nm左右的无定形磷酸钙空心颗粒。磷酸钙具有良好的生物相容性,因此这些具有空心结构特征的磷酸钙可发展为理想的载药体系。我们以牛血清蛋白(BSA)为模型体系研究了材料的载药和释放性能,发现所获得的空心纳米磷酸钙不仅具有良好的蛋白质负载量而且还具有优异的可释放性,明显优于传统的羟基磷灰石体系。     

Sodium ion internalized within phospholipid membranes

Seven phospholipids, modified with ester groups in their hydrophobic chains, were synthesized and examined for their ability to promote sodium ion flux across vesicular membranes. It was found by 23Na NMR that only the phospholipids having short chain segments beyond their terminal ester groups catalyze sodium ion transfer by up to 2 orders of magnitude relative to a conventional phospholipid, POPC. The rates increase with the concentration of the ester-phospholipid admixed with POPC in the bilayer. More surprisingly, the rates increase with the time allowed for the vesicles to age. This was attributed to ester-phospholipid migrating in the bilayers to form domains that solubilize the sodium ion within the hydrocarbon interior of the membrane. Such membrane domains explain why shift reagent-modified NMR spectra display three 23Na signals representing sodium outside the vesicles, sodium within the vesicular water pools, and sodium within the membranes themselves.     

Reduction-responsive vesicles composed of dimethylaminopropyl octadecanamide and dithiodipropionic acid

Reduction-responsive vesicle was prepared by salt-bridging N-[3-(dimethylamino)propyl]-octadecanamide (DMAPODA, a cationic amphiphile) using 3,3′-dithiodipropionic acid (DTPA, a disulfide diacid compound). According to the transmission electron micrograph and the fluorescence quenching degree (53.2%), it could be said that vesicles were formed when the DMAPODA to DTPA molar ratio was 2:2. The DMAPODA/DTPA associate was considered to be a building block for vesicle formation because DTPA could electrostatically associate with DMAPODA and help the cationic amphiphile assemble into the vesicle. On a differential scanning calorimetric thermogram, the DMAPODA/DTPA vesicle showed two endothermic peaks at 50.6°C and 63.2°C. The peak found at the lower temperature was possibly due to the solid gel-to-liquid crystal phase transition of the vesicular membrane and the peak found at the higher temperature was considered to be due to the melting of DMAPODA, indicating that unassociated DMAPODA coexisted with DMAPODA/DTPA vesicles. The release of calcein enveloped in the vesicle was promoted by DL-dithiothreitol, possibly because DTPA can be broken by the reducing agent to form mercaptopropionic acids and the vesicle could be disintegrated and/or the vesicular membrane would become defective.     

Preparation and properties of vesicles from condensable amphiphilic amino acids

Three double‐chain amphiphiles with amino acid groups as hydrophilic moiety were synthesized. These amphiphiles can be easily dispersed in buffer solution to form transparent dispersion. Examination of the dispersion by transmission electron microscopy (TEM) showed the formation of stable vesicular aggregates, which was also confirmed by the ability to encapsulate water‐soluble dyes. Since amino acid groups are located on the surface of the vesicles, water‐soluble carbodiimide can induce the condensation of these groups to form peptide. The phase transition temperatures of these vesicles were estimated by differential scanning calorimetry (DSC), and a decrease of phase transition temperature was observed after polycondensation due to the disturbance of the ordered arrangement of the hydrophobic chains. The leakage rate of the vesicles before and after condensation was studied by monitoring the increase of fluorescence intensity of water‐soluble dye. These vesicles belong to the least permeable ones and the leakage rate can be controlled by varying the degree of condensation or the temperature.     

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).     

Enhancing physical stability of positively charged catanionic vesicles in the presence of calcium chloride via cholesterol-induced fluidic bilayer characteristic

An ion pair amphiphile (IPA), hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS), and a double-chained cationic surfactant, dimethyldimyristylammonium bromide (DTDAB), could form positively charged catanionic vesicles with a potential application in gene delivery. To improve the gene delivery efficiency, the addition of CaCl₂ into cationic liposomal systems has been proposed in the literature. In this study, detrimental effect of calcium chloride on the physical stability of the positively charged HTMA-DS/DTDAB catanionic vesicles was demonstrated by the size and zeta potential analyses of the vesicles. It was noted that the reduced electrostatic interaction between the catanionic vesicles could not fully explain the lowered physical stability of the vesicles in the presence of CaCl₂. Apparently, the molecular packing/interaction in the vesicular bilayers played an important role in the vesicle physical stability. To modify the molecular packing/interaction in the vesicular bilayers, cholesterol was adopted as an additive to form catanionic vesicles with HTMA-DS/DTDAB. It was found that the physical stability of the catanionic vesicles was significantly improved with the presence of cholesterol in the vesicular bilayers even in the presence of 50 mM CaCl₂. An infrared analysis suggested that with the incorporation of cholesterol into HTMA-DS/DTDAB vesicular bilayers, the alkyl chain motion was enhanced, and the molecular packing became less ordered. The cholesterol-induced fluidic bilayer characteristic allowed the vesicular bilayers to be adjusted to a stable status, resulting in improved physical stability of the catanionic vesicles even in the presence of CaCl₂ with a high concentration.     

Copper nanoparticles in membrane mimicking vesicles-synthesis and catalytic activity

Copper nanoparticle (CuNPs) were successfully synthesized within the confined volume of niosomal vesicles. Metallic copper nanoparticles have been prepared in niosomal vesicles. The nanoparticle characteristics are guided by the specific properties of the niosomes. It has been found that the hydrophile: lipophile balance (HLB), area per molecule and gel-fluid transition temperature of the surfactants forming the niosome are important factors affecting nanoparticle characteristics. Entrapment ability, hydration volume, vesicle size and “leakiness” are the niosomal parameters that need to be optimized for nanoparticle formation. The synthesized nanoparticles function as very effective catalysts for reduction of Methylene Blue (MB) dye. This report gives a first hand account of how the particle characteristics of the CuNPs synthesized in niosomal vesicles can be related to their efficiency as catalysts. Since use of, niosomes for drug delivery and in cosmetic formations is well documented, the present work indicates the potential for prospective delivery of CuNPs via niosomes for various applications in future.     

基于硼酸/二醇识别的新型糖囊泡荧光传感器

摘要 合成了含有识别基团苯硼酸、喹啉发色团的新型双亲化合物,N-硼苄基-8-16烷基溴化喹啉（N-(boronobenzyl)-8-hexadecyloxyquinolinium bromide (BHQB)）.该化合物在可选择性溶剂中自组织成囊泡,囊泡的相变温度为52.4℃;研究了BHQB囊泡的荧光性质,结果表明：当向囊泡体系加入糖时,喹啉在425nm 峰逐渐增强而508nm峰急剧减弱,变化趋势为葡萄糖>果糖.实验结果表明,BHQB囊泡可以作为可植入、连续检测血糖浓度的荧光囊泡传感器,可望用于临床实际应用.     

Charged polypeptide vesicles with controllable diameter

We report the preparation and characterization of charged, amphiphilic block copolypeptides that form stable vesicles and micelles in aqueous solution. Specifically, we prepared and studied the aqueous self-assembly of a series of poly(L-lysine)-b-poly(L-leucine) block copolypeptides, KxLy, where x ranged from 20 to 80 and y ranged from 10 to 30 residues, as well as the poly(L-glutamatic acid)-b-poly(L-leucine) block copolypeptide, E60L20. Furthermore, the vesicular assemblies show dynamic properties, indicating a high degree of membrane fluidity. This characteristic provides stimuli-responsive properties to the vesicles and allows fine adjustment of vesicle size using liposome-based extrusion techniques. Vesicle extrusion also provides a straightforward means to trap solutes, making the vesicles promising biomimetic encapsulants.