固体脂质纳米粒研究新进展

综述固体脂质纳米粒(SLN)的制备方法、应用、存在的问题和解决方法以及发展前景，介绍基于SLN而开发的新型载体——纳米脂质载体和药脂结合物纳米粒。     

磁性纳米粒阿霉素微球制备的初探

目的:制备靶向抗癌药物即磁性纳米粒阿霉素白蛋白微球.方法:以阿霉素(ADR)、人血清白蛋白(HSA)和纳米Fe3O4为材料,采用乳化高温固化法制备出磁性纳米粒阿霉素白蛋白微球,并利用Hrtem对其包裹结合性能进行了观察,同时采用HPLC法对其载药量进行测试.结果:有效载药量为2.35%、表观载药量为3.55%.结论:采用乳化高温固化法能制备出磁性纳米粒阿霉素白蛋白微球.     

共载阿霉素和依克立达的PLGA纳米粒的制备及表征

目的 建立药物测定方法,并制备共载阿霉素和依克立达的PLGA纳米粒。方法 利用紫外分光光度法（UV）和高效液相色谱法（HPLC）分别建立阿霉素和依克立达的测定方法;采用纳米沉淀法制备共载纳米粒,通过调节两药的投药比,优化处方,考察纳米粒的粒径、形态、包封率、载药量以及体外释放。结果 阿霉素在1~40 μg/ml浓度范围内线性关系良好,标准曲线回归方程为A=0.021C+0.002,r=0.999 5; 依克立达在0.5~100 μg/ml浓度范围内线性关系良好,标准曲线回归方程为A=120 742.462 6C+1 974.570 4,r=1.000 0;通过处方优化,共载纳米粒的粒径约为50 nm,分布均一,呈圆形,阿霉素和依克立达的包封率分别为56.58%、51.66%,载药量分别为1.48%、1.85%,两药摩尔比约为1：1;体外释放缓慢。结论 分别建立了方便快捷、结果准确、重复性好的阿霉素和依克立达的检测方法,并且制备了分散性好、粒径较小的纳米粒,为后续实验提供基础。     

共载阿霉素和siRNA的还原敏感型前药纳米粒的制备及体外评价

目的：构建共载阿霉素（DOX）和siRNA的还原敏感型前药纳米粒（PSCSD NPs）,并对其理化性质、细胞摄取和体外细胞毒性进行考察。方法：采用核磁共振氢谱（1H NMR）和傅里叶红外光谱（FT-IR）对羧甲基壳聚糖-二硫键-DOX(CMCSS-DOX)进行结构表征;超声法制备PSCSD NPs,考察其粒径、载药量、包封率、血清稳定性、溶血率和体外释药特性等;采用荧光显微镜和流式细胞术考察4T1细胞对PSCSD NPs的摄取;通过MTT实验测定PSCSD NPs的体外细胞毒性。结果：1H NMR和FT-IR结果表明CMC-SS-DOX成功合成;PSCSD NPs的粒径为（155.1±4.0） nm(PDI=0.144±0.028),Zeta电位为（–29.9±1.0） mV,载药量为（8.25±0.47）%,包封率为（78.41±4.52）%;透射电镜观察PSCSD NPs为球形,且具有良好的血液相容性和血清稳定性。PSCSD NPs具有还原响应释药特性,可在肿瘤部位快速释药。细胞摄取和MTT实验结果表明PSCSD NPs可以有效共载DOX和siRNA进入肿瘤细胞内以发挥抗肿瘤作用。...     

半乳糖化阿霉素白蛋白纳米粒的制备及其质量评价

目的:制备半乳糖化阿霉素白蛋白纳米粒,并考察了其形态、粒径、载药量、包封率和体外释药特性.方法:采用相分离法制备阿霉素白蛋白纳米粒,并在其表面偶联半乳糖苷,使之成为半乳糖化白蛋白纳米粒.激光扫描电子显微镜观察纳米粒的形态,马尔文激光粒度仪测定其粒径分布.采用紫外分光光度法测定纳米粒的载药量和包封率,并初步研究其体外释药特性.结果:电镜结果显示阿霉素纳米粒呈类球型,平均粒径为316.3 nm,纳米粒载药量为3.12%,包封率达91.82%,48 h体外累积释药率为55.71%.结论:本方法制备阿霉素纳米粒工艺简单且包封率较高.体外释药结果显示半乳糖化阿霉素白蛋白纳米粒具有明显的缓释作用.     

槲皮素固体脂质纳米粒的包封率与载药量测定

目的:建立槲皮素固体脂质纳米粒(SLN)的包封率和载药量测定方法。方法:采用高速离心-高效液相色谱法。色谱柱为DiamonsiL-C18(250mm×4.6mm,5μm),流动相为甲醇-4.3%乙酸溶液(55∶45),流速为1.0mL·min-1,检测波长为254nm,柱温为30℃。结果:槲皮素检测浓度在2.0～200.0μg·mL-1范围内与峰面积积分值呈良好线性关系(r=0.9996);平均回收率为97.83%,RSD=1.03%(n=6)。该条件下,槲皮素SLN的包封率为80.2%,载药量为1.7%。结论:所建方法便捷、可靠,可用于SLN包封率与载药量的测定。     

载阿霉素碳量子点纳米粒的制备及其对人肺癌细胞A549 的体外抗肿瘤作用研究

目的　制备载阿霉素碳量子点纳米粒并考察其体外抗肿瘤作用。方法　采用水热合成法一步合成羧基化碳量子\r\n点（CDs-COOH）,阿霉素（DOX）的氨基通过酰胺反应与CDs-COOH 的羧基共价连接,合成CDs-DOX 载药碳量子点纳米\r\n粒。利用荧光分光光度计、红外光谱仪、紫外分光光度计、透射电镜对CDs-COOH 进行了研究;利用红外光谱仪、紫外分光\r\n光度计、粒度仪对CDs-DOX 进行了表征;采用MTT 法检测CDs-DOX 对人肺癌细胞A549 的毒性。结果　通过透射电镜\r\n观察CDs-COOH 呈球形,分布较均匀,平均粒径5 nm 左右,荧光分光光度计结果进一步验证其尺寸均匀这一性质,通过紫\r\n外分光光度计、红外光谱仪等确证CDs-COOH 和CDs-DOX 制备成功。MTT 实验表明,CDs-DOX 对人肺癌细胞A549 具\r\n有较强的细胞毒性。结论　载阿霉素碳量子点纳米粒CDs-DOX 具有一定的体外抗肿瘤作用,并具有开发成抗肿瘤递药系\r\n统的重要潜力。     

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。     

阿霉素壳寡糖纳米粒的制备及体外抗肿瘤研究

目的制备负载阿霉素的壳寡糖纳米粒,并研究其理化性质和体外抗肿瘤细胞毒性。方法采用离子凝胶法制备负载阿霉素的壳寡糖纳米粒;透射电镜观察纳米粒形态,激光粒度仪测定粒径和表面电位,紫外分光光度法测量包封率、载药量,考察载药纳米粒的体外释药特性;采用MTT法对载药壳寡糖纳米粒在体外乳腺癌细胞株MCF-7的细胞毒作用进行评价。结果制得的阿霉素壳寡糖纳米粒呈球形或类球形,形态较为完整,平均粒径为(136.77±1.21)nm,表面电位为(20.53±0.31)m V,包封率为(56.99±1.40)%,载药量为(15.49±0.38)%,168 h的累积释放率为72.15%;阿霉素和载药纳米粒对MCF-7细胞增殖的抑制作用存在明显的浓度和时间依赖性,且载药纳米粒对MCF-7细胞增殖的抑制作用随时间增加而逐渐强于游离阿霉素。结论此方法制备的阿霉素壳寡糖纳米粒粒径较小,药物释放具有明显的缓释作用,并具有较好的抗肿瘤作用。     

短葶山麦冬皂苷C固体脂质纳米粒的制备

目的:制备短葶山麦冬皂苷C固体脂质纳米粒(DT-13-SLN)并考察其理化性质。方法:以乳化-蒸发法制备DT-13-SLN,通过正交设计优化处方和制备工艺条件,测定其粒径、zeta电位、药物包封率和载药量,以透射电镜观察纳米粒形态,并考察DT-13-SLN的稳定性,对DT-13-SLN的冻干粉进行差示扫描量热(DSC)分析,以确定DT-13-SLN的生成。结果:纳米粒的平均粒径为128.8 nm,zeta电位为-30.0 mV,包封率为57.43%,载药量为3.48%。DSC分析表明有新的物相生成。DT-13-SLN于4℃放置1个月,粒径和包封率无明显变化。结论:本研究制备的DT-13-SLN粒径分布范围窄,稳定性良好。     

注射用葫芦素B固体脂质纳米粒的制备

目的为提高葫芦素B的疗效,降低毒性及不良反应,,制备了葫芦素B固体脂质纳米粒。方法采用高压匀质法制备葫芦素B固体脂质纳米粒。以单因素轮换法考察影响制备葫芦素B固体脂质纳米粒的处方和工艺因素,通过正交设计优化处方。结果制备的纳米粒为类球形纳米粒子,包封率质量分数为90.67%,平均粒径为135 nm。结论高压匀质法可用于制备葫芦素B固体脂质纳米粒。     

碳酸钙复合载药纳米粒的制备与表征

目的利用十六烷基三甲基溴化铵通过改变反应条件制备适当大小的碳酸钙空腔纳米球,碳酸钙复合纳米球进行海藻酸钠修饰。方法激光粒度分析仪、TEM对复合纳米球的性能进行表征,研究其制备条件对纳米粒径和纳米球质量的影响。结果在投料比固定的情况下,反应转速在1000r/min,碳酸钠和氯化钙的浓度为0.02mol/L,反应温度在20℃时空腔纳米球粒径最小,海藻酸钠修饰后的碳酸钙纳米球电位为(-27.20±0.75)mV,明显增加了复合纳米球的稳定性。结论最佳条件下制备的碳酸钙纳米粒粒径优良,可观察到明显的空腔结构,修饰后不仅增加了其稳定性,同时还实现了协同给药。     

Preparation and characterization of solid lipid nanoparticles loaded with alpha-Asarone

This work investigated the potential of solid lipid nanoparticles (SLNs) to improve oral bioavailablity and tissue uptake of a poorly soluble drug, alpha-Asarone. Ultrasonic homogenization method was employed to prepare alpha-Asarone-loaded SLNs (alpha-Asarone-SLNs). Particle size and distribution, pH, viscosity, drug incorporation and zeta potential of the SLNs were investigated. Pharmacokinetic study of oral administration to male rats at 10 mg/Kg suggested that the relative bioavailability of alpha-Asarone was significantly improved in alpha-Asarone-SLN group compared to alpha-Asarone solution group. Comparison of alpha-Asarone-SLN to alpha-Asarone control solution for alpha-Asarone concentrations in rat tissue showed an increased uptake of alpha-Asarone in brain and lung for the ARE-SLN group. These results indicate that alpha-Asarone-SLNs significantly enhance the absorption and tissue distribution of alpha-Asarone. SLNs offer a new approach to improve the oral bioavailability of poorly soluble drugs.     

左旋多巴固体脂质纳米粒的制备及包封率测定

目的:用微乳法制备左旋多巴固体脂质纳米粒(LDP-SLN),并建立包封率的测定方法。方法:通过绘制三元相图,采用微乳法制备LDP-SLN,用TEM和激光粒度仪进行了颗粒形貌和粒径分布的研究,用葡聚糖凝胶层析法分离测定包封率。对其粒径、形态、包封率等理化性质进行研究,并考察其稳定性。结果:实验制得LDP-SLN为稳定的略泛蓝色乳光的纳米混悬液,在透射电镜下显示为较为均匀的球体,激光粒度测定平均粒径为108nm,多分散系数1.153;4℃放置2个月,粒径、包封率无显著变化。包封率测定的线性范围为2～100mg·mL-1,线性良好(r=0.9999),精密度符合要求,LDP-SLN上柱洗脱后分离度和回收率均符合要求。结论:该研究中制备了物理性质较为稳定的LDP-SLN,建立了合适的包封率测定方法,并考查初步稳定性较好。     

多柔比星前体脂质体制备工艺筛选及质量考察

目的:筛选多柔比星前体脂质体制备工艺及条件,并对其性状、包封率进行考察评价.方法:运用均匀设计法筛选制备条件,葡聚糖凝胶层析法、紫外分光光度法测定包封率.结果:按照最佳处方所制得多柔比星前体脂质体粒径分布均匀,形态良好,包封率可达80%.结论:按照均匀设计法制备的多柔比星前体脂质体性状优良,检测方法可靠,制备方法简单可行,质量可控,具有广阔的应用前景.     

Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel

Context: Conventional ophthalmic solutions often eliminate rapidly after administration and cannot provide and maintain an adequate concentration of drug in the pre-corneal area.

Objectives: Above problem can be overcome by the use of in situ gel forming systems that are instilled as drops in to the eye and undergo a sol–gel transition in the cul-de-sac.

Methods: An ion sensitive polymer gellan gum was used as gelling agent which formed immediate gel and remained for extended time period. Nanoparticles of moxifloxacin, prepared by solvent evaporation, were separated by freeze drying. The rheological properties and in vitro drug release test of in situ gel loaded with nanoparticles were evaluated and compared with marketed preparation. In vitro release study demonstrated diffusion controlled release for moxifloxacin from formulations over a period of 12?h.

Results: The developed formulation was stable and showed enhanced contact time minimizing the frequency of administration. Confocal microscopy showed clear permeation of drug loaded nanoparticles across L/S of cornea.

Conclusion: The formulation of moxifloxacin was found liquid at the formulated pH and formed gel in the presence of mono or divalent cations. The gel formed in situ showed sustained drug release over a period of 10–12?h. The formulations were less viscous before instillation and formed strong gel after instilling it into cul-de-sac. It is thus concluded that by adopting a systematic formulation approach, an optimum point can be reached in the shortest time with minimum efforts to achieve desirable rheological and in vitro release property for in situ gel forming system.     

阿托伐他汀钙纳米粒的制备与质量评价

目的:制备阿托伐他汀钙纳米粒新剂型,对其性质进行研究,优选最佳工艺条件。方法:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒溶液,通过对处方优化,以载体材料用量(X₁)、有机溶剂用量(X₂)、表面活性剂用量(X₃)为自变量,利用Box Behnken设计响应面法以纳米粒粒径(Y)为响应值,优化了阿托伐他汀钙纳米粒的处方。用Malvern激光粒度分析仪测定了粒径分布和纳米粒的Zeta电位,扫描电镜分析了其形态,用高速冷冻离心法和紫外分光光度法测定了包封率和载药量。结果:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒溶液是适合的。响应面优化最优值为阿托伐他汀钙20 mg、卵磷脂178 mg、乙酸乙酯15 mL、聚山梨酯80774 mg,所制备的阿托伐他汀钙纳米粒呈类球形,其平均粒径(71.99±13.62) nm,Zeta电位为(-31.48±2.46) mV,包封率为(91.27±1.7)%,载药量(9.58±0.22)%。结论:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒处方及工艺适合,相关性质检测方法可行。     

Preparation,characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system

This article describes the preparation and characterization of solid lipid nanoparticles (SLNs) prepared with stearic acid (SLN-A) and a mixture of stearic acid and Compritol (SLN-B) as lipid matrix and poloxamer-188 as surfactant, using sodium taurocholate and ethanol as co-surfactant mixture, with a view to applying the SLN in topical ocular drug delivery. The SLNs were prepared by o/w microemulsion technique and characterized by time-resolved particle size analysis, polydispersity index, zeta(ζ )-potential, differential scanning calorimetry (DSC), IR-spectroscopy, and wide-angle X-ray diffractometry (WAXD). The results obtained in these studies were compared with SLN prepared with stearic acid alone. IR, WAXD, and DSC studies revealed low-crystalline SLN and were having positive ζ -potentials after three-months of storage. Results indicated mixed lipid-matrix produced SLN with low-crystallinity and smaller particle sizes and higher drug entrapment compared with SLN prepared with stearic acid alone, therefore SLN-B would be suitable for the preparation of nanosuspension. Nanosuspensions were subjected to rheological and physicochemical evaluation, in vitro drug release and ex vivo corneal permeation studies and their effect were evaluated on corneal hydration-level. SLN composed of stearic acid and compritol would prove to be a good ocular drug delivery system considering the smaller particle size, particle size stability, and physiologically tolerable components.     

载羟基喜树碱纳米粒的制备和体外评价

目的:制备壳寡糖接枝布洛芬(COS-g-IBU)纳米粒负载羟基喜树碱(HCPT)纳米粒,并考察其体外释药性能。方法:以1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)为偶联剂,制备壳寡糖接枝布洛芬纳米粒(COS-g-IBU NPs)。以COS-g-IBU NPs为载体,使用超声振荡技术制备负载HCPT的壳寡糖接枝布洛芬纳米粒(HCPT-COS-g-IBU NPs)。结果:透射电镜照片显示COS-g-IBU NPs和HCPT-COS-g-IBU NPs为球形,平均粒径分别为(116±2)nm和(146±5)nm,测得药物包封率为(79.24±1.18)%,载药量为(3.62±0.05)%,体外药物释放试验表明HCPT-COS-g-IBU NPs具有明显的缓释作用。结论:COS-g-IBU可作为HCPT缓释载体材料。