聚乳酸-羟基乙酸纳米粒表面功能化修饰及其应用

聚乳酸-羟基乙酸(PLGA)纳米粒表面特性是影响其体内分布的重要因素,经表面修饰的PLGA纳米粒已广泛应用于靶向给药系统研究.本文综述了PLGA纳米粒表面修饰的方法,包括共价交联、静电作用及疏水作用力等,概述了表面修饰纳米粒在非特异性生物黏附和生物渗透、特异性靶向、延长体循环时间及稳定生物活性分子方面的应用.     

壳聚糖修饰的托氟啶固体脂质纳米粒的制备

摘 要 目的： 研究托氟啶固体脂质纳米粒及壳聚糖修饰的托氟啶固体脂质纳米粒的制备方法。方法: 采用薄膜 超声分散法制备托氟啶固体纳米脂质粒（TFu-SLNs）及壳聚糖修饰的TFu-SLNs,并对纳米粒的形态、粒径和表面电位进行测定,通过单因素考察及正交设计优化制备方法,同时考察处方稳定性。结果: 薄膜 超声分散法制备的TFu-SLNs平均粒径为160.2 nm,Zeta电位为－33.12 mV,壳聚糖修饰TFu-SLNs平均粒径为400.3 nm,Zeta电位为+12.87 mV。经壳聚糖修饰后,随着壳聚糖浓度的增加,电位逐渐增大。优化后的处方重复性、稳定性良好。结论:通过采用正交设计法对TFu固体脂质纳米粒处方进行优化,得到TFu固体脂质纳米粒及壳聚糖修饰的TFu固体脂质纳米粒的优化处方。     

蛋白冠对纳米粒体内循环的影响和应用研究进展

纳米粒在检测、治疗癌症以及各种疑难杂症方面具有较佳的适用性,但单核吞噬系统可严重缩短纳米粒的体内循环时间,降低药物疗效。纳米粒进入机体后在其表面形成的蛋白冠可改变其表面性质,干扰吞噬细胞的识别,从而影响其在体内的循环时间。本文概述了蛋白冠的一般组成和形成过程,总结了纳米粒物理化学性质如粒径、表面电荷、亲水性和表面材料对蛋白冠形成的影响。蛋白冠影响纳米粒体内循环,主要在于吸附的调理蛋白促进细胞吞噬。因此,本文还介绍了应用蛋白冠促进纳米粒体内长循环的方法,通过设计合适的理化性质、表面修饰和定向设计蛋白冠,减少蛋白质在纳米粒表面的吸附。以减少纳米粒在单核吞噬系统(主要是肝脏和脾脏的吞噬细胞)的清除,实现纳米粒在体内长循环的目标。     

口服聚乙二醇修饰固体脂质纳米粒的组织分布及抗肿瘤药效学研究

目的 研究口服固体脂质纳米粒(solid lipid nanoparticle,SLN)和经聚乙二醇(polyethylene glycol,PEG)修饰后的SLN(pSLN)在小鼠体内的组织分布及药效。方法 采用水性溶剂扩散法制备SLN,用聚乙二醇单硬脂酸酯(PEG2000-SA)修饰以提供亲水基团;测定其粒径、Zeta电位、表面元素、接触角和稳定性;以DiR为荧光标记物,测定SLN及pSLN制剂经口服给药后的体内组织分布;以阿霉素为模型药物,考察口服脂质纳米给药系统的体内抗肿瘤活性及安全性。结果 SLN经PEG修饰后,得到的pSLN制剂粒径降低,Zeta电位约为-20 mV,表面亲水性及体内稳定性增加;经口服给药后,pSLN在肿瘤组织有聚集,且经PEG修饰后的纳米粒在组织中的滞留时间可显著延长;在荷瘤裸鼠模型动物上的药效学结果显示,PEG修饰口服脂质纳米给药系统在改善药效的同时,降低药物的不良反应,提高给药系统的安全性。结论 PEG修饰改善了口服纳米给药系统的生物分布及药效,提高了给药系统的安全性。     

基因壳聚糖纳米粒表面修饰和转染研究

目的:研究递送基因纳米粒表面修饰对体外基因转染的影响.方法:利用末端活化的聚乙二醇(PEG)制备PEG化基因壳聚糖纳米粒;通过两端活化的PEG将糖蛋白配基连接到纳米粒表面,完成肝靶向纳米粒的制备;用透射电镜观察表面修饰对纳米粒粒径大小、粒子形态的影响;使用蛋白质测定试剂盒测算纳米粒表面蛋白连接量;利用体外转染实验考察表面修饰对纳米粒转染活性的影响;用倒置荧光显微镜观察并用流式细胞仪测定转染结果.结果:纳米粒PEG化使转染效率大幅度升高,半乳糖基牛血清白蛋白(Galn-BSA)使体系的转染效率比PEG化纳米粒略有下降,但比不经修饰的纳米粒转染活性高.壳聚糖纳米粒的表面PEG化能提高纳米粒的体外稳定性,从而提高体外转染效率,并适合于进行冷冻干燥.结论:长循环壳聚糖基因递送纳米粒在基因治疗研究中可能会发挥重要作用.     

聚乳酸纳粒给药系统研究进展

目的：综述国内外PLA纳米粒的近期研究进展。方法：检索分析文献资料，对PLA纳米粒的制备方法、表面修饰对纳米粒性质的影响、纳米粒中药物释放的影响因素、体内研究及应用情况进行概述。结果：PLA纳米粒可作为注射、口服、直肠给药、鼻腔给药的载体，延长药物半衰期，提高药物生物利用度，改变药物体内分布，减少药物不良反应。结论：PLA纳米粒给疾病的临床治疗提供了更多的手段和可能，PLA纳米粒的研究和应用具有广阔的前景。     

聚乳酸纳米粒给药系统研究进展

目的:综述国内外PLA纳米粒的近期研究进展.方法:检索分析文献资料,对PLA纳米粒的制备方法、表面修饰对纳米粒性质的影响、纳米粒中药物释放的影响因素、体内研究及应用情况进行概述.结果:PLA纳米粒可作为注射、口服、直肠给药、鼻腔给药的载体,延长药物半衰期,提高药物生物利用度,改变药物体内分布,减少药物不良反应.结论:PLA纳米粒给疾病的临床治疗提供了更多的手段和可能,PLA纳米粒的研究和应用具有广阔的前景.     

肽功能化纳米粒在肿瘤精准诊疗中的研究进展

随着纳米粒表征技术及纳米粒表面修饰功能化技术的不断完善和发展,目前已可在纳米粒表面进行肽特殊功能化处理,实现肽修饰纳米粒的多功能化用于肿瘤成像和治疗。本文拟对肽配体功能化的制备方法、肽功能化纳米粒的主要性能以及在肿瘤精准诊疗中的应用作一综述。     

基因壳聚糖纳米粒表面修饰和转染研究

目的：研究递送基因纳米粒表面修饰对体外基因转染的影响。方法：利用末端活化的聚乙二醇(PEG)制备PEG化基因壳聚糖纳米粒;通过两端活化的PEG将糖蛋白配基连接到纳米粒表面,完成肝靶向纳米粒的制备;用透射电镜观察表面修饰对纳米粒粒径大小、粒子形态的影响;使用蛋白质测定试剂盒测算纳米粒表面蛋白连接量;利用体外转染实验考察表面修饰对纳米粒转染活性的影响;用倒置荧光显微镜观察并用流式细胞仪测定转染结果。结果：纳米粒PEG化使转染效率大幅度升高,半乳糖基牛血清白蛋白(Galn—BSA)使体系的转染效率比PEG化纳米粒略有下降,但比不经修饰的纳米粒转染活性高。壳聚糖纳米粒的表面PEG化能提高纳米粒的体外稳定性,从而提高体外转染效率,并适合于进行冷冻干燥。结论：长循环壳聚糖基因递送纳米粒在基因治疗研究中可能会发挥重要作用。     

溶剂扩散法制备丙酸倍氯米松固体脂质纳米粒溶剂扩散法制备丙酸倍氯米松固体脂质纳米粒

目的 建立一种高效的固体脂质纳米粒制备与分离方法。方法 用水性溶剂扩散法,制备得到甘油单硬脂酸酯固体脂质纳米粒。通过调节纳米粒表面Zeta电位,提高纳米粒的回收率。结果 用水性溶剂扩散法可以简便、快速制备得到含药固体脂质纳米粒,低转速离心(4 000 r·min^-1)即可达到纳米粒与分散体系之间的分离,回收率明显高于未调节纳米粒表面Zeta电位条件下的高速离心分离方法。用本法制备得到的纳米粒在最初3 h有药物的突释现象,随后4 d药物的释放明显缓慢,每天释放约药物总量的6%。结论 水性溶剂扩散法适用于固体脂质纳米粒的制备,得到的固体脂质纳米粒可实现药物的控制释放。     

Merits and advances of microfluidics in the pharmaceutical field: design technologies and future prospects

Microfluidics is used to manipulate fluid flow in micro-channels to fabricate drug delivery vesicles in a uniform tunable size. Thanks to their designs, microfluidic technology provides an alternative and versatile platform over traditional formulation methods of nanoparticles. Understanding the factors that affect the formulation of nanoparticles can guide the proper selection of microfluidic design and the operating parameters aiming at producing nanoparticles with reproducible properties. This review introduces the microfluidic systems’ continuous flow (single-phase) and segmented flow (multiphase) and their different mixing parameters and mechanisms. Furthermore, microfluidic approaches for efficient production of nanoparticles as surface modification, anti-fouling, and post-microfluidic treatment are summarized. The review sheds light on the used microfluidic systems and operation parameters applied to prepare and fine-tune nanoparticles like lipid, poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles as well as cross-linked nanoparticles. The approaches for scale-up production using microfluidics for clinical or industrial use are also highlighted. Furthermore, the use of microfluidics in preparing novel micro/nanofluidic drug delivery systems is presented. In conclusion, the characteristic vital features of microfluidics offer the ability to develop precise and efficient drug delivery nanoparticles.     

Magnetic iron oxide nanoparticles for tumor-targeted therapy

Magnetic nanoparticles have been intensively investigated due to their magnetic characteristics, quantum dot effects, as well as their potential applications in the area of bioscience and medicine. Very promising nanoparticles are magnetic iron oxide nanoparticles with appropriate surface modification which have been widely used experimentally for masses of in vivo applications such as magnetic resonance imaging contrast enhancement, drug delivery, and hyperthermia, etc.. All these biomedical applications require that these nanoparticles have effective magnetic values and suitable sizes. On the other hand, these applications need special surface modification of these particles, which not only have to be non-toxic and biocompatible, but also allow a targetable drug delivery in a specific area. This review summarizes the current research situation and development of magnetic iron oxide nanoparticles, and the biomedical applications ranging from drug delivery to hyperthermia for tumor-targeted therapy.     

介孔二氧化硅纳米粒的研究进展

介孔二氧化硅纳米粒(MSNs)具有良好生物相容性、有序介孔结构、比表面积大、表面易修饰性等特点,在很多生物医药领域显示出了极大的应用前景,尤其是基于MSNs的纳米药物输送体系被广泛用于各种药物的递送。主要介绍MSNs和可降解MSNs的制备,同时介绍了MSNs膜包被及官能团修饰在缓释控释药物中的应用,最后探讨了MSNs递进到中空介孔二氧化硅纳米粒(HMSNs)的更大的应用前景。     

Analyzing Nanotheraputics-Based Approaches for the Management of Psychotic Disorders

Psychoses are brain disorders clinically manifested by cognitive conditions such as hallucinations, delirium, dementia, schizophrenia, and delusions. Antipsychotic drugs are associated with significant side effects such as dystonia, tardive dyskinesia, involuntary muscle movement, and metabolic disorders. Moreover, those antipsychotics currently available have poor bioavailability, drug-related adverse effects, poor therapeutic efficacy, and poor brain delivery resulting from the blood-brain barrier. Conventional dosage forms, which release the drugs into the general circulation, fail to deliver the drugs directly to the brain efficiently. Thus, a rational approach based on nanotherapeutics may overcome these limitations; such approaches can be used for the delivery of drug molecules to their targeted site. Nanotherapeutics are colloidal systems comprising nanosize-range particles and unique physicochemical properties; these properties include plasticity, biodegradability, bioacceptability, versatile surface modification properties, and protection of drug molecules from degradation. The present review describes various nanoformulations for delivery of antipsychotic drugs to the brain; these include nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion, nanosuspensions, and carbon nanotubes. The review also considers the ability of these formulations to improve drug bioavailability and targeting affinity, as well as their ability to circumvent the first-pass metabolism.     

香叶木素固体脂质纳米粒的制备及质量评价

目的 制备香叶木素固体脂质纳米粒并对其进行质量评价。方法 采用溶剂注入法制备香叶木素固体脂质纳米粒,用 Box-Benhnken效应面法优化处方,并通过包封率、微观形态、粒径分布和Zeta电位对香叶木素固体脂质纳米粒的质量进行评价。 结果 香叶木素固体脂质纳米粒最优处方组成：表面活性剂浓度3.39%,棕榈酸浓度0.116%,脂药质比为21:100,制备的香叶木素 固体脂质纳米粒外观澄清透明,带淡蓝色乳光;平均粒径为(91.73±3.18)nm(n=3),PDI为0.228,电位为(-11.46±0.74)mV(n=3);包 封率为95.13%,载药量为9.04%;透射电镜照片显示纳米粒大小均一,呈球形或类球形。 结论 该处方可用于香叶木素固体脂 质纳米粒的制备,工艺简单,稳定可行。     

固体脂质纳米粒和纳米结构脂质载体在经皮给药系统中的研究进展

目的介绍固体脂质纳米粒和纳米结构脂质载体在经皮给药系统中的应用与优势,为其开发利用提供参考。方法查阅国内外相关文献共30余篇,从固体脂质纳米粒和纳米结构脂质载体用于经皮给药系统的优势、药物在固体脂质纳米粒和纳米结构脂质载体中的分布形式及固体脂质纳米粒和纳米结构脂质载体在经皮给药领域中的应用等方面进行综述。结果固体脂质纳米粒和纳米结构脂质载体可以增强药物稳定性,能在皮肤表面产生包封效应,增加皮肤水合作用,具有药物靶向性。结论固体脂质纳米粒和纳米结构脂质载体是极有发展前景的新型经皮给药系统。     

Particle Shape: A New Design Parameter for Passive Targeting In Splenotropic Drug Delivery

The role of particle size and surface modification on biodistribution of nanocarriers is widely reported. We report for the first time the role of nanoparticle shape on biodistribution. Our study demonstrates that irregular shaped polymer lipid nanoparticles (LIPOMER) evade kupffer cells and localize in the spleen. We also demonstrate the macrophage-evading characteristic of the irregular-shaped LIPOMER. Our results suggest particle shape as an important tool for passive targeting of nanocarriers in splenotropic drug delivery. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2576–2581, 2010     

Box-Behnken效应面法优化姜黄素正负离子固体脂质纳米粒的处方

目的 采用Box-Behnken效应面法筛选姜黄素正负离子固体脂质纳米粒的最优处方.方法 采用乳化蒸发-低温固化法制备姜黄素的固体脂质纳米粒,以固体脂质的质量、卵磷脂的质量和混合表面活性剂为考察对象,以包封率和脂质载药量为考察指标,利用3因素3水平Box-Behnken效应面设计法筛选姜黄素固体脂质纳米粒的最优处方.结果 按最优处方制备固体脂质纳米粒的包封率为94.20％ ±2.55％、脂质载药量为3.49％±0.11％,平均粒径为194.9 ±12.0 nm,Zeta电位为-28.15 ±2.72 mV.结论 采用Box-Behnken效应面法优化姜黄素正负固体脂质纳米粒的处方是有效、可行的.     

脂质乳剂释药机制及其靶向性的研究进展

简要介绍了脂质乳剂释药机制、体内外试验方法及影响释药特性和靶向性的因素，如粒径、药物性质、表面修饰等研究进展。     

Lipid nanoparticles with different oil/fatty ester ratios as carriers of buprenorphine and its prodrugs for injection

Buprenorphine is a promising drug for the treatment of chronic pain and opioid dependence. The aim of the present work was to evaluate the feasibility of lipid nanoparticles with different oil/fatty ester ratios for injection of buprenorphine. To improve the release properties and analgesic duration of the drug, ester prodrugs were also incorporated into the nanoparticles for evaluation. Linseed oil and cetyl palmitate were respectively chosen as the liquid lipid and solid lipid in the inner phase of the nanoparticulate systems. Differential scanning calorimetry (DSC) was performed, and the particle size, zeta potential, molecular environment, and lipid/water partitioning were determined to characterize the state of the drug/prodrug and lipid modification. The in vitro release kinetics were measured by a Franz assembly. DSC showed that systems without oil (solid lipid nanoparticles, SLNs) had a more ordered crystalline lattice in the inner matrix compared to those with oil (nanostructured lipid carriers, NLCs and lipid emulsion, LE). The mean diameter of the nanoparticles ranged between 180 and 200 nm. The in vitro drug/prodrug release occurred in a delayed manner in decreasing order as follows: SLN > NLC > LE. It was found that the release rate was reduced following an increase in alkyl ester chains in the prodrugs. The in vivo antinociception was examined by a cold ethanol tail-flick test in rats. Compared to an aqueous solution, a prolonged analgesic duration was detected after an intravenous injection of buprenorphine-loaded SLNs and buprenorphine propionate (Bu-C3)-loaded NLCs (with 10% linseed oil in the lipid phase). The Bu-C3 in NLCs even showed a maximum antinociceptive activity for 10 h. In vitro erythrocyte hemolysis and lactate dehydrogenase (LDH) release from neutrophils demonstrated a negligible toxicity of these carriers. Our results indicate the feasibility of using lipid nanoparticles, especially SLNs and NLCs, as parenteral delivery systems for buprenorphine and its prodrugs.