磁性纳米颗粒在顺铂脂质体结构中的组装

通过探讨制备过程中磁性颗粒不同的加入顺序对其在脂质体结构中分布的影响,制备了具有较高包封率的磁性顺铂(cisplatin,CDDP)脂质体。本研究采用改良水热合成方法一步制备了表面修饰的Fe3O4磁性纳米颗粒并采用薄膜超声法制备了CDDP磁性脂质体,用石墨炉原子吸收分光光度法测定CDDP含量。在制备过程中考察两种不同制备程序对脂质体微观结构的影响,即程序I:将磁性颗粒先与磷脂结合再成膜制备脂质体;程序II:将磁性颗粒分散于药物溶液中水合制备脂质体。用透射电镜(transmission electron microscope,TEM)观察磁性脂质体形态。按正交实验设计筛选最优处方制备磁性脂质体,以程序I制备的脂质体磁性颗粒分布于磷脂双层中,包封率为34.90%,而以程序II制备的脂质体磁性颗粒分布于脂质体中间水相,包封率为28.34%。两者包封率均高于普通脂质体。3种不同脂质体体外释药均符合一级释药规律。程序I制备的磁性脂质体由于磁性颗粒分布于磷脂双层中,改变了磷脂所形成的双层骨架,使其释药t1/2为9 h,比另外两者较短。结果表明,采用程序I实现了纳米磁性颗粒在脂质体中的组装,用此方法制备的磁性脂质体在药物包...     

磁性微球和磁性纳米粒的研究进展

介绍了磁靶向给药系统的主要类型、分类及组成,重点综述了磁靶向给药系统中的磁性微球和磁性纳米粒的特性、制备方法、体内外磁控试验的研究进展.     

Redox- and pH-Responsive Nanoparticles Release Piperlongumine in a Stimuli-Sensitive Manner to Inhibit Pulmonary Metastasis of Colorectal Carcinoma Cells

Redox-responsive nanoparticles having a diselenide linkage were synthesized to target pulmonary metastasis of cancer cells. Methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) was crosslinked using selenocystine-acetyl histidine (Ac-histidine) conjugates (ChitoPEGse) for stimuli-responsive delivery of piperlongumine (PL). ChitoPEGse nanoparticles swelled in an acidic environment and became partially disintegrated in the presence of H₂O₂, resulting in an increase of particle size and in a size distribution having multimodal pattern. PL release increased under acidic conditions and in the presence of H₂O₂. Uptake of ChitoPEGse nanoparticles by CT26 cells significantly increased in acidic and redox state. PL-incorporated ChitoPEGse nanoparticles (PL NPs) showed similar anticancer activity in vitro against A549 and CT26 cells compared to PL itself. PL NP showed superior anticancer and antimetastatic activity in an in vivo CT26 cell pulmonary metastasis mouse model. Furthermore, an immunofluorescence imaging study demonstrated that PL NP conjugates were specifically delivered to the tumor mass in the lung. Conclusively, ChitoPEGse nanoparticles were able to be delivered to cancer cells with an acidic- or redox state-sensitive manner and then efficiently targeted pulmonary metastasis of cancer cells since ChitoPEGse nanoparticles have dual pH- and redox-responsiveness.     

磁性纳米粒及其在药物传输体系中的应用

综述磁性纳米粒的特性、种类、制备及其表面修饰以及作为药物传输体系载体的应用研究。磁性纳米粒用作药物载体的优势在于,除了可提高药物的靶向性,降低其毒副作用,还因具磁学性质而能发挥多功能治疗作用。     

丝裂霉素C磁性纳米粒Ⅱ.大鼠体内的药动学和靶向性

评价了丝裂霉素C磁性纳米粒（1-MNP）在大鼠体内的约动学和靶向性。采用HPLC法测定大鼠肝、肾和血浆中的约物浓度。采用约物的靶向效率（DTE）、相对靶向效率（RTE）、靶向性指数（DTI）和相对靶向指数（RTI）评价了磁场作用下1-MNP在大鼠体内的靶向性。结果表明，1-MNP在磁场作用下能改变大鼠体内的药物分布，并显著增大靶器官中的药物浓度。     

丝裂霉素C磁性纳米粒Ⅰ.制备和质量评价

以丝裂霉素C（1）为模型药物，白蛋白为载体材料，Fe3O4磁流体为磁性材料制备了1磁性纳米粒（1-MNP），并对其粒径、包封率、载药量、体外磁响应性等指标进行评价。结果表明1-MNP平均粒径为61．8nm，包封率89％，载药量6％。在5000G磁场、管径0．5mm，流速0．5cm／s的条件下，1-MNP截留率可达97．6％。1-MNP在 pH7．4的磷酸盐缓冲液和生理盐水中8h释药达90％。     

Nanoparticles in drug delivery: mechanism of action,formulation and clinical application towards reduction in drug-associated nephrotoxicity

Introduction: Over the past few decades, nanoparticles (NPs) have gained immeasurable interest in the field of drug delivery. Various NP formulations have been disseminated in drug development in an attempt to increase efficacy, safety and tolerability of incorporated drugs. In this context, NP formulations that increase solubility, control release, and/or affect the in vivo disposition of drugs, were developed to improve the pharmacokinetic and pharmacodynamic properties of encapsulated drugs.

Areas covered: In this article, important properties related to NP function such as particle size, surface charge and shape are disseminated. Also, the current understanding of how NP characteristics affect particle uptake and targeted delivery is elucidated. Selected NP systems currently used in delivery of drugs in biological systems and their production methods are discussed as well. Emphasis is placed on current NP formulations that are shown to reduce drug-induced adverse renal complications.

Expert opinion: Formulation designs utilizing NP-encapsulated drugs offer alternative pharmacotherapy options with improved safety profiles for current and emerging drugs. NPs have been shown to increase the therapeutic index of several entrapped drugs mostly by decreasing drug localization and side effects on organs. Recent studies on NP-encapsulated chemotherapeutic and antibiotic medications show enhanced therapeutic outcomes by altering drug degradation, increasing systemic circulation and/or enhancing cell specific targeting. They may also reduce the distribution of encapsulated drugs into the kidneys and attenuate drug-associated adverse renal complications. The usefulness of NP formulation in reducing the nephrotoxicity of nonsteroidal anti-inflammatory drugs is an underexplored territory that deserves more attention.     

去氢骆驼蓬碱长循环磁纳米脂质体的制备及体外性质的研究

目的制备去氢骆驼蓬碱长循环磁纳米脂质体并对其体外性质进行考察。方法采用紫外分光光度法测定去氢骆驼蓬碱的质量浓度;采用逆相蒸发法制备去氢骆驼蓬碱磁纳米脂质体,并用被动载药法包裹去氢骆驼蓬碱;测定脂质体的粒径、电位、包封率、Fe2+质量浓度、释放度并进行电镜观察。结果建立了紫外分光光度法测定去氢骆驼蓬碱质量浓度的方法,去氢骆驼蓬碱在2.0~12.0μg·mL~(-1)范围内线性关系较好(r=0.999 6),回收率为102.0%。去氢骆驼蓬碱磁纳米脂质体的粒径为297.7nm;药脂比1∶10和1∶20的包封率分别为69.22%和84.55%;Fe2+质量浓度为189.1μg·mL~(-1),体外释放度符合Wuibull方程。结论被动载药法制备的去氢骆驼蓬碱长循环磁纳米脂质体包封率较高,粒径较好,体外释放度符合Wuibull方程。     

Multiple Membrane Interactions and Versatile Vesicle Deformations Elicited by Melittin

Melittin induces various reactions in membranes and has been widely studied as a model for membrane-interacting peptide; however, the mechanism whereby melittin elicits its effects remains unclear. Here, we observed melittin-induced changes in individual giant liposomes using direct real-time imaging by dark-field optical microscopy, and the mechanisms involved were correlated with results obtained using circular dichroism, cosedimentation, fluorescence quenching of tryptophan residues, and electron microscopy. Depending on the concentration of negatively charged phospholipids in the membrane and the molecular ratio between lipid and melittin, melittin induced the “increasing membrane area”, “phased shrinkage”, or “solubilization” of liposomes. In phased shrinkage, liposomes formed small particles on their surface and rapidly decreased in size. Under conditions in which the increasing membrane area, phased shrinkage, or solubilization were mainly observed, the secondary structure of melittin was primarily estimated as an α-helix, β-like, or disordered structure, respectively. When the increasing membrane area or phased shrinkage occurred, almost all melittin was bound to the membranes and reached more hydrophobic regions of the membranes than when solubilization occurred. These results indicate that the various effects of melittin result from its ability to adopt various structures and membrane-binding states depending on the conditions.     

Formation of Multilayered Vesicles from Water/Organic-Solvent (W/O) Emulsions: Theory and Practice

Multilayered liposome (MLV) formation from water/organic-solvent (W/O) emulsions was studied. A fundamental liposome population parameter, the E^ratio, was defined and used to estimate the bilayer number and water spacing in MLV liposomes. MLVs prepared from W/O emulsions have optimum drug entrapment at an emulsion-lipid/emulsion-water ratio of 0.33. Drug entrapment is typically 50 to 65% under these optimal conditions.     

Interactions Between Aminoglycosides and Phospholipids Using Liposomes: A Possible Mechanism of Nephrotoxicity

Interactions of aminoglycosides with phospholipids were estimated by the increase in turbidity of liposomes consisting of various phospholipids. The turbidity of liposomes containing negatively charged phospholipids was increased by gentamicin, the highest increase in turbidity being observed for phosphatidylinositol-4,5-diphosphate-containing liposomes. The extent of turbidity was dependent on the concentration of acidic phospholipid in the liposomal membrane as well as the number of amino groups of the aminoglycosides. The release of glucose from glucose-entrapped liposomes depended on the concentration of gentamicin. The turbidity of liposomes containing lipids extracted from rat renal cortex was also increased by aminoglycosides depending on the number of amino groups. From electron microscopic observations, the increase in turbidity of liposome suspensions was caused by liposome fusion.     

银杏内酯PELGE纳米粒的制备及理化性质

采用共沉淀法制备银杏内酯PELGE纳米粒,正交试验设计优化处方,并考察了优化制品的外观和体外释放行为.结果表明,所得纳米粒外观圆整,包封率为（66.9±1.7）%,粒径为（123.3±44.0）nm,体Pb24h累积释放率为60.2%.     

Nanoparticles for human liver-specific drug and gene delivery systems: in vitro and in vivo advances

A wide variety of nanoparticles (NPs) that can deliver incorporated therapeutic materials such as compounds, proteins, genes and siRNAs to the human liver have been developed to treat liver-related diseases. This review describes NP-based drug and gene delivery systems such as liposomes (including lipoplex), polymer micelles, polymers (including polyplex) and viral vectors. It focuses upon the modification of these NPs to enhance liver specificity or delivery efficiency in vitro and in vivo. We discuss recent advances in drug and gene delivery systems specific to the human liver utilizing bio-nanocapsules comprising hepatitis B virus (HBV) envelope L protein, which has a pivotal role in HBV infection. These NP-based medicines may offer novel strategies for the treatment of liver-related diseases and contribute to the development of nanomedicines targeting other tissues.     

褪黑素固体脂质纳米粒的制备及理化性质

考察不同的处方对褪黑素固体脂质纳米粒粒径和包封率等理化性质的影响，并进行其体外释放实验。结果表明，以单硬脂酸甘油酯为脂质材料，乳化超声法制备固体脂质纳米粒，平均粒径为（62．4±1．5）nm，ζ电位为（-7．0±0．2）mV，平均包封率为（64．6±3．8）％；药物的体外释放符合Weibull模型。     

双亲性环糊精纳米粒的制备和应用

本文阐述了双亲性环糊精纳米粒的制备、影响因素和应用，及其它衍生物在纳米粒载药系统中的应用。     

双水相萃取技术及其在药物提取分离中的应用近况

目的介绍近年来双水相萃取技术在药物提取分离中的应用情况。方法对近几年国内外文献资料进行总结和归纳,介绍了双水相萃取技术的基本原理与特点,综述了近年来该技术在蛋白质、酶、氨基酸类药物,中药体系及抗生素类药物的提取分离等方面的应用进展。结果双水相萃取技术广泛应用于药物提取分离中,取得了较大进展。结论该技术用于药物提取分离中,有着广阔的应用前景,将推动我国医药工业的发展。     

Preparation and characterization of Tegafur magnetic thermosensitive liposomes

The purpose was to study the preparation and properties of tegafur magnetic thermosensitive liposomes. The method was to employ an improved chemical coprecipitation method for preparing nano-magnetic particles and a reverse-phase evaporation and ultrasonic method for preparing tegafur magnetic thermosensitive liposomes. The results showed that tegafur magnetic thermosensitive liposomes were prepared successfully. They had comparatively strong magnetism and superparamagnetism, and their temperature showed a linear positive correlation with dosages and the field strength under a current value. The conclusion was that tegafur magnetic thermosensitive liposomes with comparatively small particle size, superparamagnetism and comparatively strong magnetism were prepared successfully.     

乙酰半胱氨酸纳米粒的制备及在小鼠体内的分布

以壳聚糖为载体,溶剂扩散法制备乙酰半胱氨酸纳米粒,制得的纳米粒呈大小均匀的球形,平均粒径(163.0±12.8)nm,包封率(81.2+1.2)%,载药量(28.9+0.4)%。用HPLC法测定了小鼠单剂量尾静脉注射乙酰半胱氨酸纳米粒或其注射液后各脏器(心、肝、脾、肺和肾)和血浆中的药物浓度,并以相对摄取量和靶向效率评价纳米粒的靶向性。结果表明,纳米粒明显改变了药物在小鼠体内的生物分布。与注射液组相比,纳米粒组在肝组织中乙酰半胱氨酸浓度明显提高,血浆、心和肾组织中的药物浓度显著降低。