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.     

Formulation and Targeting Efficiency of Cisplatin Engineered Solid Lipid Nanoparticles

The present study is aimed at the overall improvement in the efficacy, reduced toxicity and enhancement of therapeutic index of cisplatin. Solid lipid nanoparticulate delivery system of cisplatin has been developed by microemulsification method by using stearic acid, soy lecithin 95% and sodium glycolate. The formulations were then characterized with respect to size and its surface morphology, zeta potential, entrapment efficiency, in vitro drug release profile, in vivo drug targeting studies and its stability under specific conditions. The formulated solid lipid nanoparticles were oval with a diameter ranging from 250 nm to 500 nm. The lowest entrapment efficiency was found to be 47.59% and highest was found to be 74.53%. The zeta potential was in the range of -9.8 to -11.2 mv. In vitro release study was analyzed using various mathematical models. Highest cumulative percent drug release was observed with F-1 (97.22 %) and lowest with F-4 (78.43%) in 16 h. The in vivo result of formulated solid lipid nanoparticles of cisplatin reveals that the drug is preferentially targeting to liver followed by brain and lungs.     

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。     

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。     

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。     

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。     

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。     

亲水性蛋白和多肽固体脂质纳米粒的制备方法

目的近年来,随着生物技术和基因工程的进步,许多新的具有药用活性的蛋白和多肽得到了发展。然而,由于蛋白和多肽的亲水性和不稳定性,需要选择特殊的载体和制备工艺,以克服药物本身的缺陷。方法本综述描述了在优化的制备方法下,固体脂质纳米粒（SLN）作为亲水性的蛋白和多肽药物的可选择载体,用来包封亲水性蛋白和多肽。结果 SLN作为载体可以改善蛋白的稳定性,避免其水解,并能够实现药物分子的持续释放。结论因此,许多重要的多肽和蛋白已被包封进SLN或正在研究当中。     

维甲酸固体脂质纳米粒冷冻干燥工艺研究

选用不同辅料作为冻干保护剂，制备维甲酸固体脂质纳米粒冻干品，并考察不同制品的外观、粒径、包封率。以冻干品外观、再分散后的粒径和包封率为评价指标，筛选保护剂的优化处方。结果表明，选择蔗糖、蔗糖＋海藻糖、甘露醇＋海藻糖、甘露醇＋蔗糖为冻干保护剂，冻干纳米粒再分散后粒径减小，包封率与冻干前相比有所降低，含海藻糖处方可大大加快纳米粒的再分散速率，4℃和20℃放置3个月稳定性良好。     

家兔体内泊那替尼固体脂质纳米粒药代动力学研究

目的探讨泊那替尼固体脂质纳米粒(P-SLN)在体内的药代动力学行为。方法将12只新西兰兔随机分为制剂组和对照组,分别给予等剂量P-SLN和泊那替尼对照品溶液,采用高效液相色谱(HPLC)法检测泊那替尼体内血药浓度,并采用DAS 2. 0药代动力学软件对所得血药浓度数据进行拟合,得出对照组和给药组的药代动力学参数。结果 HPLC法适合于检测泊那替尼血药浓度,给药组药时曲线下面积(AUC)及AUMC分别是对照组的3. 39倍和14. 87倍,清除率为0. 29倍,体内平均滞留时间为4. 55倍,半衰期为4. 44倍。结论 P-SLN在体内缓释效果明显,可显著提高泊那替尼的生物利用度,可作为药物的新剂型。     

Atomic Force Microscopy Studies of Solid Lipid Nanoparticles

Purpose. Solid Lipid Nanoparticles (SLN) are an alternative carrier system for the controlled delivery of drugs. In most cases prednisolone loaded SLN show a biphasic release behaviour. The initial phase is characterised by a fast drug release, which is followed by a sustained drug release over several weeks. Methods. The particles are produced by high pressure homogenisation of a lipid (e.g. compritol, cholesterol) dispersed in an aqueous surfactant solution. In this study atomic force microscopy was used to image the original unaltered shape and surface properties of the particles. The crystallinity of the nanoparticles was investigated by differential scanning calorimetry. Results. The AFM investigations revealed the disc like shape of the particles. From differential scanning calorimetry data it can be concluded that the particle core is in the crystalline state. Additionally it was proven that the particles are surrounded by a soft layer. Conclusions. Thus it is conceivable that the fast initial drug release during in vitro dissolution tests takes place by drug release of the outer non-crystalline layers of the particles. The following sustained drug release can be assigned to the predisolone release of the inner crystalline particle layers.     

长春新碱固体脂质纳米粒的制备工艺优化

目的制备长春新碱固体脂质纳米粒(VCR-SLN)并优化其处方组成和制备工艺。方法单因素考察筛选载体、稳定剂及制备工艺,用正交试验进行优化,以包封率、载药量和粒径为指标,筛选最佳处方和制备工艺,并对在优化条件下制备的VCR-SLN进行质量评价。结果以单硬酸酯甘油酯为载体,大豆卵磷脂、泊洛沙姆188为乳化剂,采用复乳-溶剂扩散法制备得VCR-SLN,其平均粒径为156.3 nm,包封率为55.12%,载药量为3.09%。结论复乳-溶剂扩散法适用于制备VCR-SLN。     

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。     

葛根素固体脂质纳米粒抗肝损伤作用研究

目的 制备葛根素固体脂质纳米粒(puerarin solid lipid nanoparticles,Pue-SLN),对Pue-SLN进行体外释药考察,并探讨Pue-SLN对CCl4诱导的急性肝损伤大鼠的治疗作用。方法 采用乳化-超声分散法制备Pue-SLN。大鼠腹腔注射CCl4造成急性肝损伤模型。48只大鼠随机分成6组：正常组、模型组、甘草酸二胺阳性对照组(13.5 mg·kg^-1)、Pue-SLN高浓度组(27 mg·kg^-1)、中浓度组(13.5 mg·kg^-1)、低浓度组(6.75 mg·kg^-1)。分别测定大鼠血清中丙氨酸转移酶(ALT)、碱性磷酸酶(ALP)、天门冬氨酸转移酶(AST)的活力,肝组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)含量,计算肝脏指数,并对肝组织进行组织形态学检查。结果 Pue-SLN各剂量组均能抑制肝损伤大鼠血清中ALT、AST、ALP活性,降低肝匀浆中MDA含量,增强SOD、GSH-PX活性,改善肝组织的病理形态。结论 Pue-SLN对CCl4诱导的大鼠急性肝损伤具有治疗作用。     

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％。     

注射用地塞米松固体脂质纳米粒冻干粉末的处方与工艺研究及质量评价

目的:研究注射用地塞米松(DXM)固体脂质纳米粒(SLN)冻干粉末的处方及工艺并评价其质量。方法:优选支架剂处方,确定冻干工艺制备冻干制剂;采用高效液相色谱法测定其中DXM的含量,并对其质量进行研究。结果:以3%甘露醇作为支架剂,DXM-SLN的粒径为340nm,Zeta电位为—25·2mV,包封率为92·10%,载药量为7·10%,于2~8℃环境下可保存3个月。结论:该制备工艺简便、可行,质量控制方法准确、可靠。     

新藤黄酸固体脂质纳米粒的制备与质量评价

目的制备新藤黄酸固体脂质纳米粒并进行质量考察。方法采用正交试验设计优化处方,以高温乳化-低温固化的方法制备新藤黄酸固体脂质纳米粒。并对其包封率、形态等进行研究。结果所制得的新藤黄酸固体脂质纳米粒外观形态圆整,粒度分布均匀,平均粒径为163.3 nm,包封率为(60.1±1.1)%。结论高温乳化-低温固化的方法适用于新藤黄酸-固体脂质纳米粒的制备。     

Cytotoxicity of Solid Lipid Nanoparticles as a Function of the Lipid Matrix and the Surfactant

Purpose. Assessment of the in vitro cytotoxicity of solid lipid nanoparticles (SLNs) as a function of lipid matrix (Dynasan 114, Compritol ATO 888), and stabilizing surfactant (poloxamers, Tween 80, soya lecithin, and sodium dodecyl sulphate). Comparison with other colloidal carriers should determine their potential use in the clinic. Methods. SLNs were produced by high pressure homogenisation. Cytotoxicity was assessed by measuring the viability of HL60 cells and human granulocytes after incubation with SLNs. Particle internalisation was quantified by chemiluminescence measurements. Results. The nature of the lipid had no effect on viability; distinct differences were found for the surfactants. Binding to the SLN surface reduced markedly the cytotoxic effect of the surfactants, e.g., up to a factor of 65 for poloxamer 184. The permanent HL60 cell line— differentiated from cells with granulocyte characteristics by retinoic acid treatment—yielded results identical to freshly isolated human granulocytes. In general, the SLNs showed a lower cytotoxicity compared to polyalkylcyanoacrylate and polylactic/glycolic acid (PLA/ GA) nanoparticles. Conclusions. Because the results are identical when using human granulocytes, differentiated HL60 cells can be used as an easily accessible in vitro test system for i.v. injectable SLN formulations. The SLNs appear suitable as a drug carrier system for potential intravenous use due to their very low cytotoxicityin vitro.     

米非司酮固体脂质纳米粒的性状研究

制备并考察了米非司酮固体脂质纳米粒(SLN).结果表明,所得制品呈圆球状,粒径较均匀;x射线衍射分析表明SLN中米非司酮主要以无定形结构为主;差示扫描量热法结果表明,在较高药脂比时,SLN分散系中的药物仍以高分散状态存在.     

基于固体脂质纳米粒的UVA/UVB防晒凝胶研究

目的 针对大部分防晒产品不能阻挡全波长紫外线照射的情况,制备兼具长波紫外线（UVA）和中波紫外线（UVB）防护功能的防晒凝胶剂,研究其形貌、粒径及紫外吸收。方法 采用乳化-分散法制备防护UVB的甲氧基肉桂酸辛酯固体脂质纳米粒（solid lipid nanoparticles,SLN）（141 nm）和防护UVA的丁基甲氧基二苯酰甲烷SLN（104 nm）,添加纳米二氧化钛（TiO₂）作为物理阻挡剂,透明质酸作为凝胶基质和保湿剂。分别以粒径、紫外吸收、外观形状作为评价指标,经优化后获得UVA/UVB防晒凝胶。结果 甲氧基肉桂酸辛酯SLN和丁基甲氧基二苯酰甲烷SLN的最佳载药量分别为4%和3%,粒径分别为141,104 nm,各自在250~350,280~400 nm内有紫外吸收。最终制得的防晒凝胶剂是白色细腻的均匀乳状液,在280~720 nm内有明显紫外吸收,UVA/UVB防护效果好。豚鼠模型上证明其具有优良的防晒效果。结论 载甲氧基肉桂酸辛酯SLN和丁基甲氧基二苯酰甲烷SLN的防晒凝胶剂有望成为一种新型UVA/UVB防护剂。