醋酸地塞米松聚乙二醇化纳米粒的制备及兔体内药动学研究

目的：制备醋酸地塞米松聚乙二醇（PEG）化纳米粒,并测定其在兔体内的药动学参数。方法：以高压均质法制备醋酸地塞米松PEG化纳米粒,用扫描电镜观察纳米颗粒的形态,用激光粒度分析仪测定粒径。建立检测血浆中醋酸地塞米松浓度的HPLC法,以醋酸地塞米松溶液和普通纳米粒作为对照,测定醋酸地塞米松PEG化纳米粒在兔体内的药动学参数。结果：PEG化纳米粒平均粒径为（180±7）nm。体内半衰期为4.79h,AUC0～12为11.81mg.min.L-1,平均滞留时间为3.15h,重要药动学参数比普通纳米粒及溶液剂增加近1倍。结论：醋酸地塞米松PEG化纳米粒可以延长醋酸地塞米松在兔体内的半衰期,达到体内长循环的目的;其表观特征与普通载药纳米粒无明显差异。     

伏立康唑白蛋白纳米粒大鼠体内药动学与组织分布

摘 要 目的：制备伏立康唑白蛋白纳米粒,并考察其在大鼠体内药动学与及组织分布。 方法: 采用超高压微射流技术制备伏立康唑白蛋白纳米粒,并评价了白蛋白纳米粒的粒径分布、Zeta电位、外观形态以及体外释药行为;考察了伏立康唑白蛋白纳米粒在大鼠体内的药动学与组织分布特征。 结果: 本研究制备的伏立康唑白蛋白纳米粒平均粒径为（121.9±41.6）nm,PdI为0.197,Zeta电位为（-42.1±0.9）mV,呈球形或类球形分布;伏立康唑白蛋白纳米粒在0.5%吐温80磷酸盐缓冲液（pH 7.4）中24 h累积释放67.5%;大鼠体内药动学研究表明,伏立康唑白蛋白纳米粒和伏立康唑注射剂的AUC0-24分别为（98.27±1.42）和（105.32±1.45）g?h?L^-1,MRT0-24分别为（4.48±0.38）和（4.86±0.51）h;伏立康唑白蛋白纳米粒能增加药物在大鼠肝、脾、脑中的靶向性。 结论:伏立康唑白蛋白纳米粒在大鼠体内具有良好的肝、脾、脑中靶向性,可以提高药物治疗疗效。     

联苯双酯固体脂质纳米粒注射给药在大鼠体内的药动学

目的:研究联苯双酯固体脂质纳米粒在大鼠体内的药动学。方法:制备联苯双酯固体脂质纳米粒,大鼠尾静脉注射给药,高效液相色谱法测定不同时间血浆中联苯双酯的浓度,通过3P97程序计算药动学参数。结果:药动学研究表明联苯双酯固体脂质纳米粒消除较慢,生物利用度较高,无论是药物溶液还是纳米混悬液,在大鼠体内的药动学过程均符合二室模型。结论:与药物溶液相比,联苯双酯固体脂质纳米粒具有明显的缓释效果,同时还能提高药物的生物利用度。     

胰岛素纳米粒温敏凝胶的制备及体外释药性能

目的:制备胰岛素壳聚糖温度敏感型原位凝胶(INS-CS-NP-TISG)并进行体外释药动学考察。方法:采用离子凝胶化法制备胰岛素壳聚糖纳米粒;均匀设计法优化其处方及制备工艺,观察形态,测定粒径、表面电位、包封率和载药量;冷法配液的方法制备温度敏感型原位凝胶,改进透析袋-恒温水浴法研究胰岛素壳聚糖纳米粒温度敏感型原位凝胶溶液的体外释药动学。结果:优化制得的纳米粒呈类球形,均匀圆整,分散性好;平均粒径为(255.3±143.5)nm,在175.2~349.6nm范围内的纳米粒子达99.4%,大小均匀,分布较窄;高效液相色谱法(HPLC)测定胰岛素壳聚糖纳米粒平均包封率和载药量分别为75.84%与58.52%;表面电位(ζ)为+32.67;在人工鼻黏液中,胰岛素壳聚糖纳米粒温度敏感型原位凝胶的体外释药符合双相动力学方程,且持续释药24h。结论:选用合适的处方制备胰岛素壳聚糖纳米粒温度敏感型原位凝胶,方法简便,药物载药量高,具有较好的生物黏附性,并有一定的缓释作用。     

葛根素纳米粒在小鼠体内的药动学

目的：制备葛根素纳米粒并对其理化性质进行考察；比较葛根素纳米粒与葛根素混悬液在小鼠体内的生物利用度。方法：通过伪三元相图确定处方，通过研究葛根素纳米粒的黏度、折光率、粒径等进行质量评价；将小鼠随机分成不同的时间组，灌胃葛根素纳米粒和混悬液以及葛根素注射液，高效液相法测定不同时间小鼠血浆中药物浓度，通过3P97程序计算药动学参数。结果：纳米粒载药量为70g·L，粒径（82．3±19．1）nm；药动学参数表明葛根素纳米粒体内吸收较快，达峰时间推后，持续时间长，绝对生物利用度为50．64％。结论：本方法制备葛根素纳米粒，粒径分布均匀，稳定性好，载药量大。葛根素生物利用度较高，解决了葛根素口服利用度低的问题。     

固体脂质纳米粒的研究进展

固体脂质纳米粒的制备方法有熔融 匀质法、冷却 匀质法和微乳法等，所制备的固体脂质纳米粒的稳定性和释放机制与粒子大小、δ电位、结晶度、脂类的修饰、多种交替结构共存的特性以及药物的药动学等因素有关。目前固体脂质纳米粒可通过静脉注射、口服、肺部、经皮、经眼部以及疫苗佐剂等途径给药。限制固体脂质纳米粒临床应用的因素包括物理稳定性差、对脂溶性差的药物包封率低等，一般可通过加入离子对试剂、对药物进行PEG衍生化、β-环糊精包合等方法解决。     

紫杉醇磁性脂质体纳米粒的制备

目的研究一种制备高载药量的紫杉醇磁性脂质体纳米粒的最佳条件，并对其质量进行检测。方法 通过共沉淀法制备Fe₃O₄纳米粒，同时施加超声处理减少粒子的软团聚合，增加粒子的分散度，对粒子表面进行改性，增加与脂质的结合，最后通过微乳液-低温固化法合成紫杉醇磁性脂质体纳米粒，并通过反相高压液相色谱法检测药物的载药量和包封率。结果紫杉醇磁性脂质体纳米粒为球形或近似球形，其悬浮液样品和冻干样品的粒径约在150～170 nm，药物包封率为98.29%。结论本法制备的粒子具有高质量磁化率、良好磁响应性，符合作为纳米磁靶向给药系统的条件。     

紫杉醇白蛋白纳米粒抗肿瘤临床研究进展

以白蛋白为载体的紫杉醇纳米粒在抗肿瘤方面发挥了重要作用。本文对紫杉醇白蛋白纳米粒体内药动学过程、纳米粒转运机制进行探讨,并就近几年来紫杉醇白蛋白纳米粒在乳腺癌、非小细胞肺癌及其他恶性肿瘤方面的临床研究作一综述,为临床应用提供借鉴。     

大黄素固体脂质纳米粒在大鼠体内的药动学研究

目的：研究大黄素固体脂质纳米粒在大鼠体内的药动学。方法：采用乳化蒸发一低温固化法制备大黄素固体脂质纳米粒,将12只SD大鼠,随机分成对照组和试验组,分别注射10mg·kg-1大黄素溶液和10mg·kg-1。大黄素固体脂质纳米粒混悬液。HPLC法测定大鼠血浆中大黄素的浓度,3P97程序计算药动学参数。结果：大黄素固体脂质纳米粒消除速率较慢,其消除速率仅为大黄素溶液的0．533倍,生物利用度为大黄素溶液的1．874倍,半衰期为大黄素溶液的1．484倍,药物溶液和纳米混悬液在大鼠体内的药动学过程均符合二室模型。结论：与大黄素溶液相比,大黄素固体脂质纳米粒具有明显的缓释效果,同时提高了药物的生物利用度。     

紫杉醇固体脂质纳米粒大鼠体内药动学

目的研究紫杉醇固体脂质纳米粒在大鼠体内的药动学。方法10只健康大鼠,雌雄各半,分为2组,分别口服给药紫杉醇固体脂质纳米粒和紫杉醇乳剂30 mg.kg-1,在设计的时间点从颈静脉取血,采用RP-HPLC测定紫杉醇在全血中的药物浓度,药动学参数用3P97软件进行处理。结果大鼠口服给药后,紫杉醇固体脂质纳米粒和乳剂的tm ax分别为3.133 h和1.627 h,MRT分别为10.362 h和3.297 h,mρax分别为1.512 2 mg.L-1和0.718 9 mg.L-1。结论固体脂质纳米粒能够显著改善大鼠体内紫杉醇的药动学行为,有利于其更好地发挥抗肿瘤作用。     

PLGA nanoparticles in drug delivery: the state of the art

Nanoparticles represent drug delivery systems suitable for most administration routes. Over the years, a variety of natural and synthetic polymers have been explored for the preparation of nanoparticles, of which Poly(lactic acid) (PLA), Poly(glycolic acid) (PGA), and their copolymers (PLGA) have been extensively investigated because of their biocompatibility and biodegradability. Nanoparticles act as potential carries for several classes of drugs such as anticancer agents, antihypertensive agents, immunomodulators, and hormones; and macromolecules such as nucleic acids, proteins, peptides, and antibodies. The options available for preparation have increased with advances in traditional methods, and many novel techniques for preparation of drug-loaded nanoparticles are being developed and refined. The various methods used for preparation of nanoparticles with their advantages and limitations have been discussed. The crux of the problem is the stability of nanoparticles after preparation, which is being addressed by freeze-drying using different classes of lyoprotectants. Nanoparticles can be designed for the site-specific delivery of drugs. The targeting capability of nanoparticles is influenced by particle size, surface charge, surface modification, and hydrophobicity. Finally, the performance of nanoparticles in vivo is influenced by morphological characteristics, surface chemistry, and molecular weight. Careful design of these delivery systems with respect to target and route of administration may solve some of the problems faced by new classes of active molecules.     

The importance of nanoparticle shape in cancer drug delivery

Introduction: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy.

Areas covered: This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery.

Expert opinion: Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a current lack of understanding into the factors governing (and optimizing) the inter-relationships of size, surface characteristics and shapes of many nanoparticles proposed for use in cancer therapy.     

Pharmacokinetics and disposition of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGANPs) have been widely investigated for sustained and targeted delivery of various drugs including small molecular drugs (hydrophobic/ hydrophilic drugs) and macromolecule drugs (such as proteins, peptides, genes, vaccines, antigens, human growth factors, etc.). The in vivo pharmacokinetics and disposition profile of these encapsulated drugs and PLGANPs themselves is a key factor that determines their therapeutic index and potential for clinical use. Therefore, this review attempts to outline the in vivo behaviors of diverse drugs loaded PLGANPs administrated via different routes such as oral route, intravenous injection, nasal path, etc. Also, the associated analytical techniques used to investigate the in vivo disposition of PLGANPs loaded with drugs are focused on.     

纳米粒给药系统制备的研究进展

纳米给药系统在实现药物靶向给药,缓、控释放等方面表现出良好的应用前景,因而成为近年来药剂学领域的研究热点之一.本文综述了纳米粒(纳米球和纳米囊)的主要制备方法及其优缺点,并对纳米粒主动靶向修饰的手段进行了归纳.     

Preparation and characterization of liposomes encapsulating chitosan nanoparticles

Liposomes are an important colloidal carrier system for controlled drug delivery. However some highly hydrophilic small molecules are difficult to entrap into liposomes and store stably, resulting in poor encapsulation efficiency and fast leakage. In the present work, fluorescein sodium (FS) was used as a model drug that was loaded into chitosan nanoparticles and then encapsulated into liposomes by reverse-phase evaporation (RPV). The encapsulation efficiency, particle size, zeta potential, release in vitro and pharmacokinetics in rats were determined in order to characterize the novel drug delivery system. The entrapment efficiency was above 80% in nanoparticles (Np) and 95% in liposomes encapsulating the nanoparticles (Lip-Np). The Lip-Np was composed of soybean phospholipids, cholesterol and chitosan, which the average diameter was 202.6 nm and zeta potential was -34.8 mV. The release rate of fluorescein sodium from Lip-Np was slower than from Np and liposomes. FS in Lip-Np administered to rats exhibited prolonged circulation and higher bioavailability than FS in Np. The results indicated that liposomal release kinetics can be controlled by encapsulating nanoparticles and thus solid-cored liposomes can be used as a potential drug delivery system.     

Pharmacokinetics and biodistribution of nanoparticles

Nanoparticles show their promise for improving the efficacy of drugs with a narrow therapeutic window or low bioavailability, such as anticancer drugs and nucleic acid-based drugs. The pharmacokinetics (PK) and tissue distribution of the nanoparticles largely define their therapeutic effect and toxicity. Chemical and physical properties of the nanoparticles, including size, surface charge, and surface chemistry, are important factors that determine their PK and biodistribution. The intracellular fate of the nanoparticles after cellular internalization that affects the drug bioavailability is also discussed. Strategies for overcoming barriers for intracellular delivery and drug release are presented. Finally, future directions for improving the PK of nanoparticles and perspectives in the field are discussed.     

Solid lipid nanoparticles for targeted delivery of triclosan into skin for infection prevention

Abstract

Healthcare-associated infections (HAIs) are a concern for health service providers, exacerbated by poor delivery of antimicrobials to target sites within the skin. The dermal route is attractive for local and systemic delivery of drugs, however; permeation, penetration, and access to deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). Solid lipid nanoparticles present several benefits for topical delivery for therapeutic applications, especially via the follicular route. Hair follicles, surrounded by a close network of blood capillaries and dendritic cells, are an important target for delivery of antimicrobials and present a unique microbial nidus for endogenous infections in situations where the barrier is disrupted, such as after surgery, for example, triclosan, a broad-spectrum antimicrobial agent, was encapsulated into nanoparticles using glyceryl behenate and glyceryl palmitostearate (GP) solid lipids, and incorporating Transcutol P, a known permeation enhancer at different ratios. Optimised formulation was stable over 90?d and in vitro permeation studies using full thickness porcine ear skin showed that the lipid-based nanoparticles enhanced delivery of triclosan into the skin and could direct the agent towards hair follicles, indicating their potential as a carrier system for antiseptic dermal delivery.     

Drug targeting to infectious diseases by nanoparticles surface functionalized with special biomolecules

The potential to deliver nanoparticles directly into the targeted cells is important in the therapeutic applications for infectious diseases. The possibility of therapeutic agent being attached to the nanoparticles by chemical modification has provided a novel drug delivery option. Interestingly, the discovery of carbon nanotubes and graphene has given an excellent imaging and therapeutic agent for the biomedical applications. In spite of continuous advancement in pharmaceutical drug delivery viz. micelles, vesicles, liquid crystals, etc., during the past decades, their prohibitive production has limited their use. Nanomaterials with their properties of biodegradation, equal biodistribution, mass production, and long time storage make them attractive alternatives for future biomedical applications. Nanoparticles surface functionalized with specific biomolecules based drug delivery has driven new direction for modulating the pharmacokinetics, pharmacodynamics, biorecognition, and increasing the efficacy of targeted drugs. These new strategies are likely to minimize drug degradation and loss, increase drug availability, and opens up new vistas for drug delivery.     

Nanoparticle analysis and characterization methodologies in environmental risk assessment of engineered nanoparticles

Environmental risk assessments of engineered nanoparticles require thorough characterization of nanoparticles and their aggregates. Furthermore, quantitative analytical methods are required to determine environmental concentrations and enable both effect and exposure assessments. Many methods still need optimization and development, especially for new types of nanoparticles in water, but extensive experience can be gained from the fields of environmental chemistry of natural nanomaterials and from fundamental colloid chemistry. This review briefly describes most methods that are being exploited in nanoecotoxicology for analysis and characterization of nanomaterials. Methodological aspects are discussed in relation to the fields of nanometrology, particle size analysis and analytical chemistry. Differences in both the type of size measures (length, radius, aspect ratio, etc.), and the type of average or distributions afforded by the specific measures are compared. The strengths of single particle methods, such as electron microscopy and atomic force microscopy, with respect to imaging, shape determinations and application to particle process studies are discussed, together with their limitations in terms of counting statistics and sample preparation. Methods based on the measurement of particle populations are discussed in terms of their quantitative analyses, but the necessity of knowing their limitations in size range and concentration range is also considered. The advantage of combining complementary methods is highlighted.     

Biological properties of "naked" metal nanoparticles

Over the past few decades, inorganic nanoparticles, which exhibit significantly distinct physical, chemical and biological properties from their bulk counterpart's, have elicited much interest. Discoveries in the past decade have demonstrated that the electromagnetic, optical and catalytic properties of noble-metal nanoparticles such as gold, silver and platinum, are strongly influenced by shape and size. This has motivated an upsurge in research on the synthesis routes that allow better control of shape and size for various nano-biotechnological applications. Biomedical applications of metal nanoparticles have been dominated by the use of nanobioconjugates that started in 1971 after the discovery of immunogold labeling by Faulk and Taylor. Currently metal-based nanoconjugates are used in various biomedical applications such as probes for electron microscopy to visualize cellular components, drug delivery (vehicle for delivering drugs, proteins, peptides, plasmids, DNAs, etc), detection, diagnosis and therapy (targeted and non-targeted). However biological properties of bare-metal (naked) nanoparticles have remained largely unexplored. Therefore, in this review we discuss the novel biological properties and applications of three most widely used metal nanoparticles, namely, the nanoparticles of gold, silver and platinum. We describe the novel properties and use of these nanoparticles in angiogenesis and cancer related disorders.