固体脂质纳米粒的研究进展

固体脂质纳米粒是新一代亚微粒给药系统，由于其生理相容性好，可控制药物释放以及良好的靶向性等优点，日益受到各国研究者的重视。本文综述了固体脂质纳米粒的制备方法，体外释药，给药途径及存在问题等方面的内容。     

2种单硬脂酸甘油酯固体脂质纳米粒制剂的体内组织分布及药动学研究

目的:研究单硬脂酸甘油酯固体脂质纳米粒(MSLN)和经聚乙二醇2000(PEG2000)修饰后的MSLN(PEG-MSLN)在小鼠体内的组织分布及其在大鼠体内的药动学,考察PEG2000修饰对MSLN体内组织分布及药动学的影响。方法:采用溶剂扩散法制备MSLN,测定其粒径和Zeta电位;以罗丹明B为荧光标记物,测定和计算2种MSLN制剂经鼠尾静脉注射后的体内组织分布及药动学参数。结果:2种MSLN制剂粒径分布相似,Zeta电位约为—20mV;经鼠尾静脉注射后,MSLN靶向肝脏,且经PEG2000修饰后的纳米粒体循环时间可显著延长至2·2倍。结论:MSLN经PEG2000修饰后可改善体循环,其可作为肝脏靶向的药物载体。     

2种单硬脂酸甘油酯固体月旨质纳米粒制剂的体内组织分布及药动学研究

目的：研究单硬脂酸甘油酯固体脂质纳米粒（MSLN）和经聚乙二醇2000（PEG2000）修饰后的MSLN（PEG～MSLN）杠小鼠体内的组织分布厦其在大鼠体内的药动学，考察PEG2000修饰对MSLN体内组织分布厦药动学的影响。方法：采用溶刑扩散法制备MSLN，测定其粒径和Zeta电位；以罗丹明B为荧光标记物，测定和计算2种MSLN制剂经鼠尾静脉注射后的体内组织分布及药动学参数。结果：2种MSLN制荆粒径分布相似，Zeta电位约为一20mV；经鼠尾静脉注射后，MSLN靶向肝脏，且经PEG2000修饰后的纳米粒体循环时间可显著延长至2．2倍。结论：MSLN经PEG2000修饰后可改善体循环，其可作为肝脏靶向的药物载体。     

固体脂质纳米粒技术及其应用

固体脂质纳米粒(solid lipid nanoparticles,SLN)是20世纪90年代初发展起来的继乳剂、脂质体、微粒和毫微粒后,新一代的性能优越的亚微粒给药系统,是指粒径在10～1000nm的胶体给药系统,以毒性低、生物相容性好、生物可降解的固态天     

固体脂质纳米粒的研究进展

在新药的研发过程中,越来越多的数据显示,由于药物自身理化性质的限制,可能使一些很有希望的药物由于不符合药物动力学要求而遭淘汰.于是,脂质体、微乳、聚合物纳米粒等一系列药物载体被发展起来,并在选择性吸收和靶向给药等方面取得了显著的成就.然而以上几种给药系统又存在某些不足之处,如:生物可降解物质存在细胞毒性以及不易提高制备规模等[1].     

大黄素固体脂质纳米粒在小鼠体内的组织分布研究

目的:研究大黄素(EMO)固体脂质纳米粒(SLN)在小鼠体内的组织分布情况和肝靶向性。方法:72只小鼠分为2组,分别尾ivEMO-SLN混悬液和EMO溶液,在给药0.083、0.250、0.500、1.000、2.000、6.000h时分别取样,以高效液相色谱法测定不同时间点血浆、心、肝、脾、肺、肾中EMO的浓度,计算EMO-SLN对EMO的药物总靶向效率摄取率(re)、总靶向性(Te)。结果:肝中所得r和Te值均为最高。结论:EMO-SLN具有较高的肝靶向性,且强于EMO。     

蟾酥固体脂质纳米粒冻干针剂小鼠体内分布的研究

分别对小鼠尾静脉注射给予蟾酥冻干固体脂质纳米粒（1-SLN）及其水溶液，采用HPLC法分别测定小鼠血浆和心、肝、脾、肺、肾、脑等各脏器中的华蟾酥毒基和脂蟾毒配基浓度，以药物靶向指数（DTI）和药物选择性指数（DSI）定量评价了1—SLN冻干针剂在小鼠体内的分布情况。结果表明，1-SLN组中肝脏的DTI值均大于1，且DSI值均大于1水溶液组的相应值，说明1-SLN具有较好的肝靶向性。     

NGR肽修饰的紫杉醇固体脂质纳米粒的制备及评价

目的本文旨在制备载紫杉醇的肿瘤靶向肽NGR修饰的固体脂质纳米粒(PTX/NGR-SLN)并对其进行评价。方法通过将DSPE-PEG_(2000)Mal与NGR偶联得到DSPE-PEG_(2000)-NGR;采用乳化-超声法制备SLN;以合成的DSPE-PEG_(2000)-NGR对SLN进行表面修饰,制得NGR-SLN,并对其进行表征。以荷HT-1080裸鼠为肿瘤模型,通过活体成像观察NGR-SLN在体内的分布情况,并考察其抑制肿瘤生长情况。结果 PTX/NGR-SLN的粒径(113.28±10.33)nm,Zeta电位为(-5.65±0.47)mV;包封率为(91.28±0.47)%,载药量为(2.48±0.28)%;释放度结果表明PTX/NGR-SLN具有良好的缓释特性;在-20℃条件下放置3个月,其粒径和包封率无明显变化。与对照组相比,PTX/NGR-SLN具有明显的肿瘤靶向递送能力和肿瘤生长抑制能力。结论 PTX/NGR-SLN具有良好的肿瘤靶向治疗潜力能力。     

汉黄芩素固体脂质纳米粒在大鼠体内的药动学及组织分布

摘 要 目的:研究汉黄芩素固体脂质纳米粒在大鼠体内的药动学及组织分布情况。方法: 大鼠随机分成汉黄芩素注射液组和汉黄芩素固体脂质纳米粒组,分别于给药后不同时间采血测定汉黄芩素含量,并测定两组大鼠心、肝、脾、肺、肾中汉黄芩素含量,计算靶向效率以评价其在大鼠体内的组织分布及靶向性。结果:汉黄芩素固体脂质纳米粒在大鼠体内的药动学模型符合二室模型,主要药动学参数为：t_1/2α=（0.551 0±0.124 7）h, t_1/2β=(14.589 1±1.563 8)h, CL=(0.006 4±0.001 4) ml·h·Kg^-1, AUC_0→∞=(125.76±9.5728) mg·h·L^-1,其在肝脏、脾脏、心脏、肺脏及肾脏的靶向效率分别为2.003、1.789、0.634、0.707、0.259。结论:与汉黄芩素溶液相比,汉黄芩素固体脂质纳米粒能提高对肝脏、脾脏的趋向性,有利于提高其治疗作用。     

固体脂质纳米粒的制备和载体结构的研究进展及其应用

目的:从固体脂质纳米载体的制备和结构特征方面介绍其研究进展.方法:以国内外大量有代表性的论文为依据进行分析、归纳整理.结果:固体脂质纳米粒的多种制备方法各有优缺点,其中以高压乳化法和微乳化法被推崇.以固体和液体的混合脂质为基材,制备出O/F/W结构的纳米粒,不但能够有较好的载药能力,还可以拥有优异的缓控释功能.结论:固体脂质纳米粒是一种性能优异、有发展前景的新型给药系统.     

Body Distribution of Camptothecin Solid Lipid Nanoparticles After Oral Administration

Purpose. The aim of this study was to investigate the specific changes in body distribution of camptothecin (CA) through incorporation into solid lipid nanoparticles (SLN) by peroral route. Methods. Camptothecin loaded solid lipid nanoparticles (CA-SLN) coated with poloxamer 188 were produced by high pressure homogenization. The CA-SLN were characterized by transmission electron microscopy and electrophoretic mobility measurement. In vitro release characteristics of camptothecin from CA-SLN were studied at different pH media. The concentration of camptothecin in organs was determined using reversed-phase high-performance liquid chromatography with a fluorescence detector after oral administration of CA-SLN and a camptothecin control solution (CA-SOL). Results. Our results showed that CA-SLN had an average diameter 196.8 nm with Zeta potential of –69.3 mV. The encapsulation efficiency of camptothecin was 99.6%, and in vitro drug release was achieved up to a week. There were two peaks in the camptothecin concentration-time curves in plasma and tested organs after oral administration of CA-SLN. The first peak was the result of free drug and the second peak was indicative of gut uptake of CA-SLN after 3 hours. In tested organs, the area under curve (AUC) and mean residence time (MRT) of CA-SLN increased significantly as compared with CA-SOL, and the increase of brain AUC was the highest among all tested organs. Conclusions. The results indicate SLN could be a promising sustained release and targeting system for camptothecin or other lipophilic antitumor drugs after oral administration.     

Solid Lipid Nanoparticles in Lymph and Plasma After Duodenal Administration to Rats

Purpose. To evaluate the uptake and transport of solid lipid nanoparticles (SLN), which have been proposed as alternative drug carriers, into the lymph and blood after duodenal administration in rats. Methods. Single doses of two different concentrations of aqueous dispersions of unlabelled and labelled SLN (average diameter 80 nm) were administered intraduodenally to rats. At different times, samples of lymph were withdrawn by cannulating the thoracic duct and blood was sampled from the jugular vein. Monitoring continued for 45 and 180 minutes, for unlabelled and labelled SLN respectively. The biological samples were analysed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and gamma-counting. Results. TEM analysis evidenced SLN in lymph and blood after duodenal administration to rats; the size of SLN in lymph did not change markedly compared to that before administration. The labelled SLN confirmed the presence of SLN in lymph and blood. Conclusions. The uptake and transport of SLN in the lymph, and to a lesser extent in the blood, were evidenced. The in vivo physical stability of SLN may have important implications in designing drug-carrying SLN.     

Simvastatin Solid Lipid Nanoparticles for Oral Delivery: Formulation Development and In vivo Evaluation

Solid lipid nanoparticles have been increasingly utilised for improving oral bioavailability of drugs. Simvastatin is biopharmaceutical class 2 drug with poor oral bioavailability of 5%. In the present study, simvastatin solid lipid nanoparticles were successfully prepared by hot melt emulsification process and optimised with respect to surfactant and lipid concentration, and drug loading. The nanoparticles were characterised for entrapment efficiency, particle size, morphology, crystallinity and thermal behavior. Optimised formulations prepared from solid lipids glyceryl behenate and glyceryl palmitostearate containing Tween 80 as surfactant exhibited satisfactory entrapment efficiencies above 96% and mean particle size below 200 nm. The electron micrographs indicated that lipid nanocarriers were almost spherical in appearance. X-ray diffraction and differential calorimetric studies proved that the drug was amorphised in the lipid matrix and did not crystallise out. To improve the physical as well as chemical stability of formulations, dry adsorbed nanoparticles were prepared by evaporative drying method using a carrier. The adsorbed nanoparticles demonstrated good flow properties and satisfactory reconstitution properties. Pharmacodynamic studies of simvastatin solid lipid nanoparticles revealed improved reduction in total cholesterol values as compared to pure drug powder indicating improved bioavailability.     

硫酸长春新碱固体脂质纳米粒的制备及其性质考察

目的以单硬脂酸甘油酯为载体材料,采用复乳溶剂挥发法制备硫酸长春新碱固体脂质纳米粒(VCR-SLN),并考察其理化性质。方法采用复乳溶剂挥发法制备VCR-SLN,以正交设计优化处方及制备工艺,并考察其形态、粒径、Zeta电位、包封率、载药量和体外释放。结果 VCR-SLN为类球形实体粒子,平均粒径为(144.83±2.71)nm,Zeta电位为(-24.77±0.513)mV,包封率为(40.54±0.45)%,载药量为(1.14±0.074)%。药物体外释放曲线符合Weibull方程。结论复乳溶剂挥发法适用于制备硫酸长春新碱固体脂质纳米粒。     

黄豆苷元固体脂质纳米粒的制备及其性质考察

目的制备黄豆苷元固体脂质纳米粒并考察其性质。方法采用正交实验法优化黄豆苷元固体脂质纳米粒的最佳处方,并测定黄豆苷元固体脂质纳米粒的粒径、ζ电位、包封率、稳定性和累积释放百分率。结果黄豆苷元固体脂质纳米粒的最佳处方组合为：单硬脂酸甘油酯用量为2.0%,黄豆苷元用量为2.0 mg.mL-1,豆磷脂的用量为0.4%,Pluronic F68的用量为1.2%。所制得的纳米粒包封率为84.7%、平均粒径为170 nm、ζ电位为-35.8 mV、72 h累积释放百分率为90.3%。结论新制黄豆苷元固体脂质纳米粒的粒度分布范围窄,包封率较高,稳定性良好。     

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。     

HPLC法测定槲皮素固体脂质纳米粒的含量

目的建立HPLC法测定槲皮素固体脂质纳米粒含量的方法。方法色谱柱:Diamonsil C18柱,流动相:甲醇-4.3%乙酸溶液(55∶45),流速:1.0mL.min-1,检测波长:254nm,进样量:20μL,柱温:30℃。结果槲皮素在20.0~200.0μg.mL-1范围内线性关系良好,平均回收率为98.6%,RSD=1.18%,结论本方法快捷、简便、准确、专属性强,可用于槲皮素固体脂质纳米粒的质量控制。     

固体脂质纳米粒的研究进展

以生理相容的高熔点脂质为骨架材料制备的固体脂质纳米粒（solid lipid nanoparticels,SLN)是近年来研究十分活跃且极有发展潜力的靶向－控释给药系统的载体,本文综述了迄今SLN研究历程中一些主要发现,包括制备及影响因素,结构,稳定性,降解与释药,已研究的剂型等,指出了它的发展前景和尚待解决的问题。     

咪喹莫特固体脂质纳米粒的制备及体外透皮作用

考察了以Precirol ATO5为脂质材料制备的咪喹莫特固体脂质纳米粒（SLN）的理化性质。载药SLN粒径88．3～112．8nm，多分散指数0．061～0．288，ζ电位-0．72～3．13mV，包封率50．2％～52．5％。分别考察了自制咪喹莫特乳膏及其SLN的体外透皮情况。结果表明，两者8h累积透皮量无显著性差异，持续透皮24h，SLN在局部皮肤中的药物滞留量为乳膏的1．55倍。     

西罗莫司固体脂质纳米粒的制备及在大鼠体内的相对生物利用度

采用溶剂扩散法制备西罗莫司固体脂质纳米粒，考察了分散介质和投药量对纳米粒粒径、表面电位、包封率的影响。将西罗莫司固体脂质纳米粒对正常SD大鼠给药，以口服液为对照，通过测定血药浓度的经时变化，考察固体脂质纳米粒的相对生物利用度。结果表明，以0．2％胆酸钠为分散介质的制品，ζ电位绝对值比以0．2％聚乙烯醇为分散相的制品显著增大，包封率由97．3％降至62．9％。处方中投药量增加，包封率下降。与口服溶液剂相比，西罗莫司固体脂质纳米粒的达峰时间tmax无明显改变，但峰浓度Cmax提高了约1．2倍，相对生物利用度为口服液的139．0％。