脑靶向纳米药物递释系统研究进展

血脑屏障(blood-brain barrier, BBB)是中枢神经系统内的一种特殊结构,其优良的屏障特性能够保护大脑免于血液循环中有害大分子及病原体的侵害。然而,这一屏障同时也限制了药物递送的效果,并成为治疗神经退行性疾病、脑胶质瘤等脑部疾病的新药开发过程中最严峻的挑战之一。近年来,纳米技术的突破使得各类纳米颗粒(nanoparticles, NPs)逐渐得到了广泛的运用,在靶向递药领域被用做药物载体,经各种途径辅助药物实现BBB的跨越。本文主要通过阐述BBB的复杂成分和特殊特性,以理解跨越BBB的难点及可能途径;同时还介绍了目前用于药物递送系统的NPs的3种主要类型:聚合物型(polymeric-based)、仿生型(biomimetic-based)及无机型(inorganic-based)NPs;在靶向递药策略方面,本文主要介绍了吸附介导(adsorptive-mediated)、载体介导(carrier-mediated)及受体介导(receptor-mediated)的胞吞作用,并在文末对脑靶向纳米递药系统的未来发展进行了展望。     

纳米控释抗癌药物研究进展

与普通抗癌药物相比，纳米控释抗癌药物具有可靶向输送、缓释药物、延长给药时间和减少毒副作用等优点，因而具有广阔的应用前景。本文针对目前国内外正在研究并取得一定进展的纳米控释抗癌药物，进行了较全面容观的综述。     

医用纳米控释系统的研究进展

医用纳米控释系统作为药物、基因传递和控释的载体,是一种新型的控释体系。安与微米粒子载体的主要区别是超微小体积,它能穿过组织间隙并被细胞吸收,可通过人体最小的毛细血管,还可通过血脑屏障,因而作为新的控释体系而被广泛研究,具有广阔的发展前景。本文重点论述了纳米控释系统在药物和基因载体方面的最新研究进展,并对其发展前景提出展望。     

肿瘤靶向纳米递药系统的研究进展

该文就纳米粒的发展、纳米技术在肿瘤靶向药物递送中的应用进行综述,并对其存在的问题和发展趋势进行了探讨.     

甲基纤维素基温敏水凝胶在生物医学领域的研究进展

甲基纤维素（MC）是一种半柔性纤维素醚衍生物,其水凝胶温敏可逆,生物相容性良好,功能可调,其应用在生物医学领域备受关注。本文对甲基纤维素温敏水凝胶在生物医学领域的应用进展进行了综述。在对甲基纤维素的凝胶化机制及凝胶化影响因素进行论述的基础上,重点介绍了甲基纤维素基水凝胶在生物医学领域的应用进展,包括在药物递送、再生医学及其他方面等的应用,列表总结了相关领域的成果,为后续研究提供思路和方向。最后,还讨论了甲基纤维素基多功能水凝胶材料的未来发展。     

中性粒细胞介导的递送系统研究进展

中性粒细胞是循环系统中数量最多,最主要的杀伤病原体的细胞,且最先到达感染部位。中性粒细胞既参与初始免疫又在破坏性炎症反应中充当效应细胞。中性粒细胞在人体内的丰度和它的固有性质都使它具备靶向炎症部位递送药物的能力,它们在炎症反应中的重要作用使得人们越来越多地关注中性粒细胞的治疗潜力。主要从利用中性粒细胞作载体、中性粒细胞外泌体作载体以及体内利用中性粒细胞特性靶向递送药物方面综述了中性粒细胞介导的药物递送系统的研究进展。     

载药纳米微粒的临床应用研究进展

载药纳米微粒是纳米技术与现代医药学结合的产物 ,是一种新型的药物输送载体。它缓释药物、延长药物作用时间 ,透过生物屏障靶向输送药物 ,建立新的给药途径等等 ,在药物控释方面显示出其他输送体系无法比拟的优势。近年来载药纳米微粒在临床各个领域的应用基础研究势头强劲 ,并取得了可喜的成绩。本文综述了载药纳米微粒在临床各领域应用的研究成果 ,并对其发展应用前景进行展望     

体外研究聚合物P(DLLA-co-TMC)的降解性能与释药行为

目的 研究P(DLLA-co-TMC)聚合物的体外降解性能与释药行为,且探讨该聚合物作为长效避孕释放载体的可行性.方法 以PBS溶液为溶媒研究P(DLLA-co-TMC)的降解性能;以P(DLLA-co-TMC)聚合物为载体制备含孕二烯酮的载药片,并通过蒸馏水浸泡载药片研究载药体系的体外释药行为.结果 P(DLLA-co-TMC)聚合物前期降解较慢,第30天和第90天失重率分别为10.0%和12.3%,后期降解速率较快,第120天的失重率为59.3%;P(DLLA-co-TMC)的载药片前期释药速率较大,出现"暴释现象",后期释药速率减缓并逐渐趋于平稳,第100天时累计释放率为5.64%.结论 P(DLLA-co-TMC)聚合物降解性能良好、释药效果明显,有望通过体内研究使含孕二烯酮的P(DLLA-co-TMC)聚合物载药系统应用于长效埋植避孕.     

基因治疗中的核酸药物及非病毒递送载体的研究进展

基因治疗是针对基因异常相关疾病的终极治疗技术,各种具有不同机制的核酸药物的出现为基因治疗带来了更多的可能性。但是,由于存在体内稳定性差、难以高效进入靶细胞等问题,核酸药物需要载体的帮助而进入目标细胞并到达特定的胞内位置,因此,开发安全高效的核酸递送系统是基因治疗的基石。与病毒载体相比,非病毒载体具有更高的安全性,但转染效率较低。随着纳米技术的发展,非病毒载体的效率得到了显著的提升,进入临床研究的数量逐渐增多。本文简要介绍基因治疗中的核酸药物及其递送载体,对非病毒核酸药物递送技术的瓶颈及进展做综合评述。     

刺激反应性释药系统的研究进展

刺激反应性释药系统（SSDDS）是一种新型的药物载体。它能够感知人体病理、生理的变化（pH值、温度）或者体外施加的信号（超声、磁信号）,然后根据信号变化调节自身的理化性质,进而调控释放其所携带的药物。SSDDS可由水凝胶、脂质体及磁性纳米微球等制备而成。与非刺激反应性释药系统相比,它具有反馈调节,可控性更强,靶向治疗作用更显著等优点。将对近年来刺激反应性释药系统的研究进展作一综述。     

Designing Nanoparticle-based Drug Delivery Systems for Precision Medicine

Traditional drugs are facing bottlenecks of lower solubility, absorption, and especially the inefficient organs or cells targeting during the precision medicine era. It is urgently needed to discover and establish new methods or strategies to modify old drugs or create new ones against the above defects. With the support of nanotechnology, the solubility, absorption and targeting of traditional drugs were greatly improved by modifying and fabricating with various types of nanoparticles to some extent, though many shortages remain. In this mini-review we will focus on advances in several most commonly used nanoparticles, from their nature and design, to drug delivery system and clinical application, that they overcome heterogeneous barriers in precision medicine, thereby ultimately improve patient outcome overall.     

磁导向阿霉素-羧甲基葡聚糖磁性毫微粒的研究

以阿霉素(ADR)为药物模型,制备了带有弱负电性的阿霉素-羧甲基葡聚糖磁性毫微粒(ADR-CMD MNPs),对比研究了静脉给药后其与电中性的ADR-dextran MNPs在小鼠肝、脾组织的富集情况,系统考察了ADR-CMD MNPs的理化性能和体内外的磁定位效果。结果表明,ADR-CMD MNPs的平均粒径为56 nm;载药量为12.4%;质量磁化率为1.06×10     

白蛋白纳米颗粒的制备研究进展

由于可以增强药物的靶向性、降低游离药物的毒副作用,基于纳米颗粒的药物递送系统在医学领域具有广泛应用。白蛋白是血浆中含量最多的蛋白质, 具有生物相容性好、无免疫原性、可生物降解等特性, 是制备纳米颗粒的理想材料。现有白蛋白纳米颗粒的制备方法主要有去溶剂化法、自组装法、乳化法、双乳化法、热凝胶、喷雾干燥、nab^TM技术、pH凝聚法等。由于制备原理及制备条件的差异,各方法表现出的优缺点也不尽相同。综述近年来白蛋白纳米颗粒的制备研究进展, 按照制备方法分类进行介绍, 并对当前白蛋白纳米颗粒研究领域所面临的困境及未来的发展方向进行探讨。     

Microfabricated Drug Delivery Systems: Concepts to Improve Clinical Benefit

Important classes of drugs have yet to benefit from advances in drug delivery technology. Strategies to provide reasonable oral bioavailability of peptide and proteins drugs remain elusive, for example. Systemic cancer drugs produce dose-limiting toxicities largely due to their lack of selectivity. Although delivery systems such as immunotoxins and liposomes improve selectivity of a few cancer drugs, current technology is not suitable for the vast majority of such molecules. Systems able to mimic the body's natural feedback mechanisms for secretion of hormones such as insulin represents yet another unmet medical need. Microfabrication techniques may permit the creation of drug delivery systems that possess a combination of structural, mechanical, and perhaps electronic features which may surmount some of these challenges. In this review, drug delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells—as a possible treatment for diabetes—and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug-loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs. Similarly designed particles with sizes in the 2–10 m range may be safe to administer intravenously and a clinical strategy is suggested for using such microparticles for treating solid tumors. Although hypothetical now, work is in progress to prove the concepts presented here and to validate the intuitive belief that there is an important place for microfabricated systems in drug delivery.     

Microneedle Transdermal Drug Delivery Systems for Allergen-Specific Immunotherapy,Skin Disease Treatment,and Vaccine Development

Transdermal drug delivery systems (TDDSs) overcome the hurdle of an intact skin barrier by penetrating the skin to allow molecules through. These systems reduce side effects associated with conventional hypodermic needles. Here, we introduce novel microneedle (MN) TDDSs that enhance drug delivery by creating micron-sized pores across the skin. Many MN TDDSs designed to deliver a diverse array of therapeutics, including allergen-specific immunotherapy, skin disease treatments, and vaccines, are under pre-clinical and clinical trials. Although epicutaneous approaches are emerging as new options for treating food allergy in many clinical trials, MN TDDSs could provide a more efficient and convenient route to deliver macromolecules. Furthermore, MN TDDSs may allow for safe vaccine delivery without permanent scars. MN TDDSs are a major emerging strategy for delivering novel vaccines and treatments for diseases, including skin diseases, allergic diseases, and so on.     

Sugar Micro Needles as Transdermic Drug Delivery System

We designed and fabricated an array of sugar micro needles of the length ranging from 150 μ m to 2 mm for transdermic delivery of drugs. Micro needles were molded out of maltose mixed with pharmaceutical material, being expected bio-degradable in the human skin. To test basic tolerance to the healthy human skin, a clinical experiment was carried out for 10 healthy adult volunteers. 500 μ m-needles containing 5 wt% of ascorbate-2-glycoside were inserted into the skin of the forearm and snapped off to be left in the skin. They spontaneously dissolved by hydrolysis to release ascorbate in the epidermis and the dermis. No dermatological problems were observed in terms of the International Contact Dermatitis Research Group criteria. These observations indicate that the present system is a novel approach to achieve transdermic drug delivery.     

Continuous On-Chip Micropumping for Microneedle Enhanced Drug Delivery

Microneedles are promising microfabricated devices for minimally invasive drug delivery applications. Needles can be integrated into a variety of devices. However, any portable drug delivery device with integrated microneedles will need an equally compact means to deliver therapeutics. This work presents microneedles integrated with an on-chip MEMS positive displacement micropump for continuous drug delivery applications. The generation and collapse of thermally generated bubbles with flow rectified by directional check valves are used to achieve net pumping through the device. Visualization methods have observed net flow rates of water out of a microneedle at approximately 2.0 nl/s with a pressure of 3.9 kPa. In addition, continuous pumping was achieved for more than 6 hours with the heaters actuating for over 18 hours (15,000 cycles) without failing.     

A Novel Method for Efficient Drug Delivery

Local delivery of anti-thrombotic and anti-restenotic drugs is desired to achieve high concentrations of agents which may be rapidly degraded systemically or which exhibit very short half-lives in vivo. In this article, the operating characteristics of a novel local drug delivery method are described and its effectiveness demonstrated computationally and experimentally. Computational models used a finite volume method to determine the concentration field. Optical dye density measurements of Evans blue in saline were performed in an in vitro steady flow system. Modeling parameters were kept in the physiologic range. Experimental flow visualization studies demonstrated high concentrations of infusate near the vessel wall. Computational studies predicted high, clinically significant drug concentrations along the wall downstream of the infusion device. When the radial infusion velocity is large (infusion flow rate, Q_inf > 0.5% of the main flow rate, Q), the wall concentration of the infused drug remains high, e.g., levels are greater than 80% of the infusate concentration 5 cm downstream of the infusion device. At lower infusion rates (Q_inf < 0.001Q), the drug concentration at the wall decreases exponentially with axial distance to less than 25% of the infusate concentration 5 cm downstream of the infusion device, although therapeutic drug levels are still readily maintained. The near wall drug concentration is a function of flow conditions, infusion rate, and the drug diffusivity. Good agreement was obtained between computational and experimental concentration measurements. Flow simulation and experimental results indicate that the technique can effectively sustain high local drug concentrations for inhibition of thrombosis and vascular lesion formation.     

Reduction‐Sensitive Self‐Aggregates as a Novel Delivery System

Methoxy PEG amine with molecular weight of 5k and ε‐caprolactone with molecular weight of 1 960 were conjugated to a peptide comprising three cysteine residues. The shift of peak molecular weight and narrow molecular weight distribution in GPC trace without any noticeable shoulder as well as ¹H NMR analysis confirmed the successful synthesis of the copolymer. A modified O/W dialysis system was employed to prepare self‐aggregates having the size around 210 nm. During the dialysis, stabilized aggregates were obtained by intermolecular disulfide bonds via oxidation. Critical aggregate concentration (CAC) of the copolymer was determined as 0.07 mg · mL^?1 and disulfide‐stabilized self‐aggregates remained stable regardless of the concentration without displaying CAC. Doxorubicin‐loading amount and efficiency was 8.7 and 26.0%, respectively. Release profile of doxorubicin below CAC at 37 °C showed a sustained release and the addition of D ,L ‐dithiothreitol (DTT) after 24 h triggered a burst release of doxorubicin. Intermolecular disulfide bonds via oxidation stabilized the polymeric aggregates even in the diluted condition similar to that in the bloodstream and addition of DTT destabilized the aggregates to burst encapsulated doxorubicin in the reductive condition.

     

可注射原位给药体系在蛋白类药物给药中的应用

可注射进入病灶部位并能原位给药的体系具有操作简单、局部给药、延长药物释放时间、减少用药剂量等诸多优点.近年来,各国研究者竞相研究可注射原位给药体系,并将其作为亲水性大分子药物尤其是蛋白类药物的药物载体.本文主要介绍了热塑性糊状体、原位交联聚合物体系、原位聚合物沉淀和热诱导凝胶体系四种缓释药物体系,着重讨论了将其作为蛋白类药物载体的优缺点.