剪切活化纳米颗粒药物靶向治疗主动脉病变

本文探究了一种剪切活化纳米颗粒药物靶向递送策略,可用于辅助治疗主动脉缩窄和主动脉瘤。基于理想化的主动脉缩窄和主动脉瘤的三维几何模型,考虑了脉动血流与主动脉壁面的流固耦合作用,利用病变主动脉内局部独特的血流动力学环境实现纳米颗粒药物的靶向输运,搭载纳米颗粒药物的微米载体将被局部异常的剪切率激活进而靶向释放纳米颗粒药物。本文初步论证了剪切活化纳米颗粒药物靶向输运策略在主动脉病变治疗中的可行性,研究结果可以为设计药物输运系统和开发新型治疗方法提供理论依据。

溶剂蒸发法制备支化聚合物基疏水药物纳米颗粒

文章研究了在有机溶剂(如乙醇)中,通过溶剂蒸发制备疏水性药物纳米颗粒的方法及制备的纳米材料。以具有生物相容性的支化聚(乙二醇)-b-(N-异丙基丙烯酰胺)聚合物纳米为支架,装载不同疏水药物,经过溶剂蒸发,得到稳定的纳米药物,同时能很方便地溶解在水中得到水性药物纳米颗粒分散体。研究表明:疏水性药物纳米颗粒中,酮洛芬药物纳米颗粒(Dh≈200nm),可以在溶液中稳定保存9个月;当药物与聚合物质量比为0.33∶1时产率可达96%,质量比为1∶1时产率可达到80%。采用透射电子显微镜(transmission electron microscope,TEM)、动态光散射仪(dynamic light scattering,DLS)表征了药物纳米的尺度和结构。

纳米载体逆转肿瘤耐药的研究进展

联合化疗对恶性肿瘤患者有积极的意义,但肿瘤细胞产生的耐药性又是肿瘤化疗失败最常见而又最难解决的问题之一。肿瘤细胞产生耐药性是多方面的,其中以多药耐药性(Multidrug resistance,MDR)最为常见。MDR使药物从靶细胞中清除或阻断发挥药效的途径,是癌症治疗的重大障碍之一。纳米颗粒药物传递系统(DDS)是一种潜在的逆转MDR的工具,可以通过靶向针对多药耐药的肿瘤细胞本身或肿瘤的内皮细胞来实现功能。本文就逆转MDR中DDS的应用进行了综述。

双重pH响应超轻度交联支化聚合物纳米材料的合成及对大黄素的载药应用

采用寡聚乙二醇甲基丙烯酸酯(OEGMA)、甲基丙烯酸二乙胺乙酯(DEAEMA)和原酸酯结构单元构建超轻度交联支化共聚物PODO及其纳米材料,并对大黄素(RE)的载药/释药进行了研究。PODO聚合物纳米材料的制备方法简单,无需自组装,且具有双重pH响应性:在中性水液中稳定,而在pH 5.5时,纳米颗粒会发生先变大后解离的双重响应过程。以大黄素为模型药物,进行了相关载药及pH响应释药研究,包载率达到35.2%。释药实验表明,在pH 7.0时,药物纳米颗粒相对稳定;在pH 5.5时,经48 h药物释放率达87%。

Alginate-Coated Fe3O4 Hollow Microspheres for Drug Delivery

Novel hollow Fe3O4 nanoparticles for drug delivery were synthesized via a one-step template- free approach. These nanoparticles were obtained by modifing the Fe3O4 nanoparticles with 3-aminopropyltrimethoxy silane, and then grafting alginate onto the surface of amine magnetic. The hollow structure of Fe3O4 spheres was characterized by TEM, XRD, and XPS. The M-H hysteresis loop indicated that the magnetic spheres exhibit snperparamagnetic characteristics at room temperature. Daunorubicin acting as a model drug was loaded into the carrier, and the maximum percent of envelop and load were 28.4% and 14.2% respectively. The drug controlled releasing behaviors of the carriers were compared in different pH media.

New research on development of solid lipid nanoparticles

To review the latest research development of the solid lipid nanoparticles(SLN) according to the recent relevant literatures.Each preparations of the SLN have advantages and disadvantages.Among the total preparations of the SLN.the high pressure homogenization(HPH) and the microemulsion tech- nique are to praise highly.The drug incorporation and release profiles could be modified as adjustment of production parameters.The SLNis an excellent drug delivery system and has broad prospects in the phar- maceutical field.

Research progress in nanoparticles as anticancer drug carrier

Nanoparticles drug delivery system has sustained and controlled release features as well as targeted drug delivery, which can change the characteristics of drug distribution in vivo. It can increase the stability of the drug and enhance drug bioavailability. The selective targeting of nanoparticles can be achieved through enhanced permeability and retention effect and a conjugated specific ligand or through the effects of physiological conditions, such as pH and temperature. Nanoparticles can be prepared by using a wide range of materials and can be used to encapsulate chemotherapeutic agents to reduce toxicity, which can be used for imaging, therapy, and diagnosis. In this research, recent progress on nanoparticles as a targeted drug delivery system will be reviewed, including positive-targeting, negative-targeting, and physicochemical-targeting used as anticancer drug carriers.

Spectroscopic Investigated Interaction between Silver Nanocomposites Based of Poly-N-Vinylpyrrolidone and Doxorubicin for Drug Delivering

It is investigated to synthesis of Ag nanoparticles by presence the synthetic polymer poly-N-vinylpyrrolidone. It was determined with X-ray analyses that the size ofnanoparticles changed between 18-42 nm. Then, the authors studied sorption process of doxorubicine by silver nanocomposites and investigated chemical interaction between antibiotic and poly-N-vinyplyrrolidone with UV-VIS （ultraviolet visible） and FT-IR （Fourier transform infrared） spectroscopy. It is shown that formation of the nanoparticles doxorubicin complex mainly occurs in the 190-208 nm wavelengths on polymers 〉C=O functional groups. Also, the four main absorbing peaks of doxorubicin--234, 253, 288 and 495 nm undergo chemists shift （A2 = 12-15 nm）. When increases to pH = 7-8, the size of Ag-doxorubicin particles decreases. It is determined that the 410 nm absorption peak of Ag nanoparticles undergo 409-418 nm interval and the 3,500, 1,600, 1,645 and 1,190 sm^-1 absorption lines of PVPr （polymer poly-N-vinylpyrrolidone） slightly altered.

基于HPMCAS载体的依非韦伦固体分散体溶出模式研究

目的以依非韦伦为原料药、不同规格(L、M、H)HPMCAS为载体,采用喷雾干燥法制备固体分散体并对其溶出模式进行初步探究。方法通过X射线粉末衍射(XRPD)、扫描电子显微镜(SEM)对固体分散体理化性质进行制剂学表征;以动力溶解度为指标考察不同药载比、不同规格HPMCAS固体分散体的溶出情况;通过粒度分析仪和透射电子显微镜(TEM)、SEM探讨固体分散体溶出时的不同模式。结果XRPD分析显示,固体分散体中药物以无定形的形态分散在HPMCAS中;SEM分析显示,L、M、H规格HPMCAS与依非韦伦形成的固体分散体均具有“萎缩葡萄干”形态;在pH 6.8磷酸缓冲盐溶液中溶出时,药载比1∶6的固体分散体溶出好,药载比1∶1.5的固体分散体溶出差且相同药载比时L规格HPMCAS的固体分散体溶出更快。结论以不同规格HPMCAS为载体制备的依非韦伦固体分散体在pH 6.8磷酸缓冲盐溶液中溶出时,存在多种溶出模式。药载比1∶6时,L、M规格HPMCAS的固体分散体以药物纳米颗粒的形式溶出;药载比1∶1.5时,L、M规格HPMCAS的固体分散体存在类似溶蚀的溶出模式,药物从载体骨架中释放。

Biological identity of nanomaterials:Opportunities and challenges

The emergence of nanoparticles(NPs)has attracted tremendous interest of the scientific community for decades due to their unique properties and potential applications in diverse areas,including drug delivery and therapy.Many novel NPs have been synthesized and used to reduce drug toxicity,improve bio-availability,prolong circulation time,control drug release,and actively target to desired cells or tissues.However,clinical translation of NPs with the goal of treating particularly challenging diseases,such as cancer,will require a thorough understanding of how the NP properties influence their fate in biological systems,especially in vivo.Many efforts have been paid to studying the interactions and mechanisms of NPs and cells.Unless deliberately designed,the NPs in contact with biological fluids are rapidly covered by a selected group of biomolecules especially proteins to form a corona that interacts with biological systems.In this view,the recent development of NPs in drug delivery and the interactions of NPs with cells and proteins are summarized.By understanding the protein-NP interactions,some guidelines for safety design of NPs,challenges and future perspectives are discussed.

Surface-modulated and thermoresponsive polyphosphoester nanoparticles for enhanced intracellular drug delivery

The chemical structure of end groups influenced the phase transition temperature of thermoresponsive polymers. We demonstrated a strategy for the preparation of the pH/thermo-responsive polymeric nanoparticles via subtle modification of end groups of thermoresponsive polymer segments with a carboxyl group and revealed its potential application for enhanced intracellular drug delivery. By developing a polymeric nanoparticle composed of poly(aliphatic ester) as the inner core and thermoresponsive polyphosphoester as the outer shell, we showed that end groups of thermoresponsive polyphosphoester segments modified by carboxyl groups exhibited a pH/thermo-responsive behavior due to the hydrophilic to hydrophobic transitions of the end groups in response to the pH. Moreover, by encapsulating doxorubicin into the hydrophobic core of such pH/thermo-responsive polymer nanoparticles, their intracellular delivery and cytotoxicity to wild-type and drug-resistant tumor cells were significantly enhanced through the phase-transition-dependent drug release that was triggered by endosomal/lysosomal pH. This novel strategy and the multi-responsive polymer nanoparticles achieved by the subtle chain-terminal modification of thermoresponsive polymers provide a smart platform for biomedical applications.

Phenylboronic acid modified mucoadhesive nanoparticle drug carriers facilitate weekly treatment of experimentally- induced dry eye syndrome

Topical formulations, commonly applied for treatment of anterior eye diseases, require frequent administration due to rapid clearance from the ocular surface, typically through the lacrimal drainage system or through over-spillage onto the lids. We report on a mucoadhesive nanoparticle drug delivery system that may be used to prolong the precorneal residence time of encapsulated drugs. The nanoparticles were formed from self-assembly of block copolymers composed of poly（D, L-lactide） and Dextran. The enhanced mucoadhesion properties were achieved by surface functionalizing the nanoparticles with phenylboronic acid. The nanoparticles encapsulated up to 12 wt.% of Cyclosporine A （CycA） and sustained the release for up to five days at a clinically relevant dose, which led us to explore the therapeutic efficacy of the formulation with reduced administration frequency. By administering CycA-loaded nanoparticles to dry eye-induced mice once a week, inflammatory infiltrates were eliminated and the ocular surface completely recovered. The same once a week dosage of the nanoparticles also showed no signs of physical irritation or inflammatory responses in acute （1 week） and chronic （12 weeks） studies in healthy rabbit eyes. These findings indicate that the nanoparticles may significantly reduce the frequency of administration for effective treatment of anterior eye diseases without causing ocular irritation.

Recent advances in biological detection with magnetic nanoparticles as a useful tool

Magnetic nanoparticles have emerged as a powerful tool for magnetic resonance imaging, biodetection, drug delivery, and hyperthermia. This review focuses on the biological detection of magnetic nanoparticles as well as their physicochemical properties. Substantial progress in the sensitivity of detection has been made by developing variety of methods. Five applications of magnetic nanoparticles in biological detection are discussed in this review: magnetic separation, magnetic sensing, magnetic manipulation, magnetic catalysis, and signal enhancer for surface plasmon resonance(SPR). Finally, some future trends and perspectives in these research areas are outlined.

Metallic nanoparticles analysis for the blood flow in tapered stenosed arteries： Application in nanomedicines

Blood flow model is recycled to study the influence of magnetic field and nanoparticles in tapered stenosed arteries. The metallic nanoparticles for the blood flow with water as base fluid are not explored so far. The representation for the blood flow is through an axially non-symmetrical but radially symmetric stenosis. Symmetry of the distribution of the wall shearing stress and resistive impedance and their growth with the deve- loping stenosis is another important feature of our analysis. Exact solutions have been evaluated for velocity, resistance impedance, wall shear stress and shearing stress at the stenosis throat. The graphical results of different types of tapered arteries （i.e. conver- ging tapering, diverging tapering, non-tapered artery） have been examined for different parameters of interest for pure water and Copper water （Cu-water）.

Gadofullerene nanoparticles extend survival rate and down-regulate thrombin expression in orthotopic pancreatic cancer

Pancreatic cancer is a devastating malignant disease with 5-year survival rate less than 8%.The impenetrable desmoplastic stroma of pancreatic tissue and serious side-effects of existing drugs hinder the effective treatment for pancreatic carcinoma.Thus,it is imperative to exploit much more safe and efficient methods to prolong the survival of pancreatic cancer patients.In this study,we explored a superior anti-pancreatic cancer strategy based on gadofullerene nanoparticles(GFNPs)using an orthotopic human pancreatic carcinoma(PANC-1)tumor model.It was demonstrated that GFNPs could efficiently suppress orthotopic pancreatic cancer in a dose manner,and significantly extend the survival rate of tumor-bearing mice.Of note,the proteomic profiling of tumor tissues revealed that GFNPs ameliorated the coagulation cascade dysfunction and downregulated the thrombin expression in pancreatic tumor tissues.The regulation of abnormal thrombin by GFNPs was validated in vitro and in vivo.More importantly,GFNPs suppressed orthotopic pancreatic cancer with negligible adverse effects,superior to the widely recognized clinical antipancreatic cancer drug,gemcitabine.Together,this study provides a promising therapeutic for intractable pancreatic cancer as well as a potential to alleviate the cancer-associated thromboembolic diseases.

Magnetic drug delivery systems

There has been unprecedented progress in the development of biomedical nanotechnology and nanoma- terials over the past few decades, and nanoparticle-based drug delivery systems （DDSs） have great potential for clin- ical applications. Among these, magnetic drug delivery systems （MDDSs） based on magnetic nanoparticles （MNPs） are attracting increasing attention owing to their favor- able biocompatibility and excellent multifunctional loading capability. MDDSs primarily have a solid core of super paramagnetic maghemite （y-Fe^03） or magnetite （Fe304） nanoparticles ranging in size from 10 to 100nm. Their surface can be functionalized by organic and/or inorganic modification. Further conjugation with targeting ligands, drug loading, and MNP assembly can provide complex magnetic delivery systems with improved targeting efficacy and reduced toxicity. Owing to their sensitive response to external magnetic fields, MNPs and their assemblies have been developed as novel smart delivery systems. In this review, we first summarize the basic physicochemical and magnetic properties of desirable MDDSs that fulfill the requirements for specific clinical applications. Secondly, we discuss the surface modifications and functionalization issues that arise when designing elaborate MDDSs for future clinical uses. Finally, we highlight recent progress in the design and fabrication of MNPs, magnetic assemblies, and magnetic microbnbbles and liposomes as MDDSs for cancer diagnosis and therapy. Recently, researchers have focused on enhanced targeting efficacy and theranostics by applying step-by-step sequential treatment, and by magnetically mod- ulating dosing regimens, which are the current challenges for clinical applications.