口服载药纳米粒的研究进展

综述近年来口服载药纳米粒的有关研究进展，着重从制备方法、表面修饰、药物释放及应用几个方面进行介绍。作为一种新型给药系统，纳米粒在口服给药方面具有广阔的开发及应用前景。     

载药纳米粒的研究进展

综述了聚合物、固体脂质及长循环3种纳米粒的载体材料、制备方法的研究进展。     

载药纳米粒在干粉吸入剂中的应用

本文分析了载药纳米粒在干粉吸入剂上缺乏商业吸引力的原因,以及与常规干粉吸入剂相比存在的优势;介绍了纳米粒-载体复合物、大粒径中空纳米粒聚集体两种干粉吸入剂的制备方法及形成机制。由于纳米粒干粉吸入制剂具备优良的分散性能和肺沉积性能,并同时拥有纳米粒作为药物载体的独特性能,使其在干粉吸入剂上具有强大的优势和广阔的发展空间。     

壳聚糖-磷脂自组装纳米粒载药系统的研究进展

本文综述了壳聚糖-磷脂自组装纳米粒作为新型药物递送系统的研究进展,阐述其自组装过程的关键机制,揭示了所得纳米粒独特的核-壳结构及该结构与包载药物之间的相互作用关系;总结了相关制备方法,并对经典的溶剂滴入法进行了详细说明.在此基础上,全面归纳了壳聚糖-磷脂自组装纳米粒在递送抗肿瘤药、抗炎药、多肽类药物、降脂药、抗菌药及基...     

mRNA脂质纳米粒载药系统的构建及体外评价

目的 构建脂质纳米粒DLin-LNP,以EGFP-mRNA为模型药,考察DLin-LNP对于mRNA的体外递送能力。方法 采用薄膜水化法制备DLin-LNP, 并进一步制备 DLin@mRNA,对纳米粒进行表征,使用激光扫描共聚焦显微镜观察脂质纳米粒胞内的分布情况,以RM-1细胞为模型考察胞内转染情况。结果 成功制备了脂质纳米粒DLin-LNP,其粒径为（151.1±2.1） nm,空载电位为（23.7±0.5） mV。DLin-LNP在RM-1细胞中转染mRNA效率较高,其毒性远低于市售脂质体Lipo8000_,且 DLin-LNP脂质纳米粒稳定性好。结论 DLin-LNP具有高转染效率和安全性,且稳定性好,可作为mRNA递送载体,为后续脂质纳米粒肿瘤治疗中的应用提供依据。     

超临界辅助喷雾法用于固体脂质纳米粒的制备

目的采用超临界辅助喷雾制粒法制备固体脂质纳米粒,并考察工艺与处方因素对纳米粒理化性质的影响。方法采用自制超临界喷雾制粒设备,制备硬脂酸脂质纳米粒,考察硬脂酸浓度、超临界流体CO2与载体溶液流量比、喷嘴孔径等对固体脂质纳米粒粒径的影响,筛选合适的处方工艺参数;以亲水性大分子药物胰岛素为模型药物,制备载药固体脂质纳米粒,评价纳米粒的粒径、电位、包封率、释放度等理化性质。结果制备得到的纳米粒粒径与载体浓度、超临界流体CO2与载体溶液流量比、喷嘴孔径有关,通过处方工艺的调节,可制得平均粒径〈300nm的固体脂质纳米粒;制得的胰岛素固体脂质纳米粒的平均粒径约300nm,包封率72．2％,载药量为3．44％,载药纳米粒在体外可实现12h缓慢释放;处方中加入泊洛沙姆可减小纳米粒粒径和粒度分布,但药物的包封率降低,并且突释现象更明显。结论超临界辅助喷雾制粒法可用于固体脂质纳米粒的制备,并能够对亲水性药物实现有效的包封和释放的调节。     

聚乳酸及其共聚物脑靶向载药纳米粒的研究进展

目的：综述聚乳酸及其共聚物（PLA/PLGA）脑靶向载药纳米粒（NP）的研究进展。方法：查阅2005-2012年来国内外有关文献,对PLA/PLGA脑靶向载药NP的作用机制、制备方法、功能分子的连接方式、体外体内作用效果评价方法进行综述。结果与结论：受体介导入脑是目前最为成熟的脑靶向给药机制,鼻腔给药也是一种有效的入脑机制;脂溶性载药NP和水溶性载药NP的制备分别采用乳化溶剂挥发法和复乳法;而溶剂扩散法可加快微球的形成,用于制备粒径较小的NP;功能分子主要利用其上的巯基、氨基、羧基或马来酰亚胺等活性基团与PLA或PLGA对应基团进行共价结合,或利用生物素-亲和素体系脑靶向递药;体外效果评价常用大鼠脑微血管内皮细胞（BMVEC）单层培养模型及BMVEC-星形胶质细胞共培养模型;体内效果评价常用荧光显微镜和活体荧光成像、放射自显影法,前者用于考察以荧光素和香豆素等荧光染料标记的脑靶向NP,后者用于以125I、3H、14C等放射性核素标记的脑靶向NP。提高脑靶向的靶向效率、提高载药量、减少PLA/PLGA的用量、改善PLA/PLGA纳米粒体内降解性能和增加稳定性,是今后脑靶向PLA/PLGA载药NP研究的重点方向。     

不同载药方法对介孔二氧化钛纳米粒载药及药物溶出速率的影响

目的考察不同载药方法对介孔二氧化钛纳米粒载药系统载药和溶出速率的影响。方法通过溶剂挥干法、熔融法、吸附平衡法分别将卡维地洛包载于介孔二氧化钛纳米粒中,用扫描电镜和透射电镜观测样品形貌,氮气吸附-解吸法测量载体的比表面积和孔体积,差示扫描量热法分析药物粒子的存在状态,X-射线衍射法进行物相分析,热失重法分析载药量,最后测定载药系统的溶出速率并进行长期稳定性试验。结果三种载药方法均能通过改变药物的存在状态使药物以非晶型存在于载体中而达到提高溶出速率的目的。其中溶剂挥干法所得的载药系统溶出速率提高显著,并且更具有长期稳定性。结论溶剂挥干法为介孔二氧化钛纳米粒载药的首选。     

载药纳米粒透过血脑屏障机制的研究进展

血脑屏障是维持中枢神经系统内环境稳定的结构基础,有效保护脑组织避免外源性有害物质侵害,但也阻碍许多治疗药物进入脑内,限制了中枢神经系统药物的临床应用。如何有效透过血脑屏障成为此类药物发挥治疗作用的关键环节。纳米粒作为一种新型药物载体,能携载药物透过血脑屏障进入脑组织,提高脑内药物浓度,实现脑内靶向给药。本文对载药纳米粒及其透过血脑屏障机制的研究进展作一综述。     

载阿霉素海藻酸钠纳米粒的制备及体外释药行为研究

目的以海藻酸钠(sodium alginate,ALG)为材料,制备载阿霉素海藻酸钠纳米粒(doxorubicin loading nanoparticles,DOX-ALG-NPs),并对其载药、释药特性进行研究。方法采用微乳-离子交联法制备空白海藻酸钠纳米粒(ALG-NPs),以吸附法载药制备阿霉素海藻酸钠纳米粒(DOX-ALG-NPs)。采用效应面法对ALG-NPs的处方进行优化,并考察ALG-NPs悬液浓度、药载比、孵育时间及孵育温度对ALG-NPs载药性能的影响。对DOX-ALG-NPs的基本性质及体外释药行为进行考察。结果成功制备了粒径为(262.0±4.5)nm的ALG-NPs及粒径为(159.8±8.1)nm、包封率及载药量分别为(94.2±0.5)%和(19.05±0.085)%的DOX-ALG-NPs。与原料药DOX相比,DOX-ALG-NPs在生理盐水与PBS(pH=7.4)中均呈现明显的缓释作用,在生理盐水和PBS中2 h与5 h时分别释放药物(38.1±1.5)%与(55.5±1.1)%、(40.0±1.8)%与(48.1±2.5)%,24 h时分别释放(73.1±3.2)%、(60.3±3.4)%。结论所制备的DOX-ALG-NPs形态圆整,粒径小且分布均匀,包封率及载药量较高,具有缓释性能,有望用作抗癌药物传递系统。     

载药纳米微粒的研究进展

载药纳米微粒是纳米技术与现代医药学结合的产物,是一种新型的药物和基因输送载体。它具有缓释药物、透过生物屏障靶向输送药物、将 DNA导入细胞浆质内和建立新的给药途径等优势。     

Separation of drug-loaded nanoparticles from free drug by gel filtration

A suitable method for separating free drug and other residual compounds from drug-loaded, colloidal polymeric particles was developed. The objective of this separation procedure was to purify particle suspensions on a preparative scale by a rapid, simple, and exact method without changing the properties of the particles. The gel filtration method described in this paper using a middle-pressure chromatographic system is able to meet all these requirements. The separation process could be optimized by using only water as an eluent in combination with Sephadex G 50 medium. The purified particles appeared after 12-13 min in the eluate. Neither dispersity nor particle size or loading rate were influenced to a considerable extent.     

The manufacturing techniques of drug-loaded polymeric nanoparticles from preformed polymers

Over the past few decades, nanoparticle (NP) formulation has been the subject of extensive research. The choice of a suitable NP formulation technique is dependent on the physicochemical properties of the drug, such as solubility and chemical stability. Different NP manufacturing methods enable modification of the physicochemical characteristics such as size, structure, morphology and surface texture, but also affect the drug loading, drug entrapment efficiency and release kinetics. This review covers an update on the state of art of the manufacturing of polymeric NPs from preformed polymers. Both, conventional methods for NP preparation, such as spontaneous formulation and emulsification-based methods, and new approaches in NP technology are presented. A comparative analysis is given for polymer, drug and solvent nature, toxicity, purification, drug stability and scalability of the method. The information obtained allows establishing criteria for selecting a method for preparation of NPs according to its advantages and limitations.     

Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles

Polymeric nanoparticles have been extensively studied as particulate carriers in the pharmaceutical and medical fields, because they show promise as drug delivery systems as a result of their controlled- and sustained-release properties, subcellular size, and biocompatibility with tissue and cells. Several methods to prepare nanoparticles have been developed during the last two decades, classified according to whether the particle formation involves a polymerization reaction or arises from a macromolecule or preformed polymer. In this review the most important preparation methods are described, especially those that make use of natural polymers. Advantages and disadvantages will be presented so as to facilitate selection of an appropriate nanoencapsulation method according to a particular application.     

Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells

Published toxicology data on chitosan nanoparticles (NP) often lack direct correlation to the in situ size and surface characteristics of the nanoparticles, and the repeated NP assaults as experienced in chronic use. The aim of this paper was to breach these gaps. Chitosan nanoparticles synthesized by spinning disc processing were characterised for size and zeta potential in HBSS and EMEM at pHs 6.0 and 7.4. Cytotoxicity against the Caco-2 cells was evaluated by measuring the changes in intracellular mitochondrial dehydrogenase activity, TEER and sodium fluorescein transport data and cell morphology. Cellular uptake of NP was observed under the confocal microscope. Contrary to established norms, the collective data suggest that the in vitro cytotoxicity of NP against the Caco-2 cells was less influenced by positive surface charges than by the particle size. Particle size was in turn determined by the pH of the medium in which the NP was dispersed, with the mean size ranging from 25 to 333 nm. At exposure concentration of 0.1%, NP of 25 ± 7 nm (zeta potential 5.3 ± 2.8 mV) was internalised by the Caco-2 cells, and the particles were observed to inflict extensive damage to the intracellular organelles. Concurrently, the transport of materials along the paracellular pathway was significantly facilitated. The Caco-2 cells were, however, capable of recovering from such assaults 5 days following NP removal, although a repeat NP exposure was observed to produce similar effects to the 1st exposure, with the cells exhibiting comparable resiliency to the 2nd assault.     

Freeze-drying of drug-free and drug-loaded solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) of a quality acceptable for i.v. administration were freeze-dried. Dynasan 112 and Compritol ATO 888 were used as lipid matrices for the SLN, stabilisers were Lipoid S 75 and poloxamer 188, respectively. To study the protective effect of various types and concentrations of cryoprotectants (e.g. carbohydrates), freeze-thaw cycles were carried out as a pre-test. The sugar trehalose proved to be most effective in preventing particle growth during freezing and thawing and also in the freeze-drying process. Changes in particle size distribution during lyophilisation could be minimised by optimising the parameters of the lyophilisation process, i.e. freezing velocity and redispersion method. Lyophilised drug-free SLN could be reconstituted in a quality considered suitable for i.v. injection with regard to the size distribution. Loading with model drugs (tetracaine, etomidate) impairs the quality of reconstituted SLN. However, the lyophilisate quality is sufficient for formulations less critical to limited particle growth, e.g. freeze-dried SLN for oral administration.     

Preparation and evaluation of drug-loaded gelatin nanoparticles for topical ophthalmic use.

Gelatin nanoparticles encapsulating pilocarpine HCl or hydrocortisone as model drugs were produced using a desolvation method. The influence of a number of preparation parameters on the particle properties was investigated. For the pilocarpine HCl-loaded spheres, an influence of the pH during particle preparation on the size was observed. Slightly negative zeta potential values were measured for all samples. In the case of pilocarpine HCl-loaded spheres, no influence of the gelatin type or the pH level was observed, which could be attributed to the shielding effect of ions present in the dispersion medium. When hydrocortisone was entrapped, a difference in zeta potential value between gelatin type A and gelatin type B particles was measured. A high pilocarpine HCl entrapment was established. Hydrocortisone was complexed with cyclodextrins in order to increase its aqueous solubility. The drug encapsulation was lower than in the case of pilocarpine HCl, but still amounted to approximately 30-40%. Compared to the aqueous drug solutions, a sustained release for both drugs was observed. The release kinetics of pilocarpine HCl are close to zero order, and no significant differences were measured between the various preparations. In the case of hydrocortisone, the release data suggests a difference in release rate depending on the type of cyclodextrin employed.     

载药藻酸纤维的抗菌性及药物吸附工艺

目的 评价负载新型载药藻酸钙纤维的抗菌性能,探索藻酸盐纤维有效吸附抗菌药物的简便工艺,为该纤维在医用敷料领域的进一步开发应用奠定基础。 方法 将葡萄糖酸氯己定和藻酸钠的共混溶液通过湿法纺丝技术,制备成新型载药藻酸钙纤维（葡萄糖酸氯己定负载的藻酸钙纤维）。以金黄色葡萄球菌和铜绿假单胞菌为试验菌株,研究载药藻酸钙纤维在干态、半湿态及湿态下的阻菌性能,采用琼脂平皿扩散法对纤维抑菌性进行评价,在扫描电子显微镜下观察纤维对试验菌的吸附状况。采用喷涂法及Box-Behnken设计在实验室条件下探索使纯藻酸盐纤维有效吸附醋酸氯己定的简便工艺。结果 新型载药藻酸钙纤维在干态下对两种实验菌均具有明显的阻碍抑制;在半湿态下当γ为107cfu/mL时,4#纤维阻碍实验菌透过生长;在湿态下金黄色葡萄球菌γ=108cfu/mL,铜绿假单胞菌γ=106cfu/mL,4#纤维对金黄色葡萄球菌和铜绿假单胞菌具有良好阻菌性。随着载药量的增加,载药纤维表面积增大,抑菌圈面积增大,对菌体的吸附力增强。实验室条件,采用喷涂法可以使得藻酸盐纤维有效吸附抗菌药物。结论 新型载药藻酸钙纤维对于革兰氏阳性菌和革兰氏阴性菌均具有良好的阻菌性和抑菌性,有望应用于医用敷料。     

载药磁性纳米微粒靶向治疗恶性肿瘤的研究与临床应用

随着纳米材料和纳米技术的发展,一种将载药磁性纳米微粒用作抗肿瘤靶向治疗已成为可能,并以其增加药物对靶细胞的指向性,降低对正常细胞的毒性和治疗安全性等诸多优越特性倍受国内外广泛关注。