脂质体载药性能与卵磷脂的关系

探讨了卵磷脂对脂质体载药性能的影响。用逆相蒸发法制备阿糖胞苷脂质体,通过测定脂质体的包封率、平均粒径和药物渗漏量,考察了蛋黄卵磷脂、大豆卵磷脂及猪脑卵磷脂对脂质体载药性能的影响。实验结果表明,在n(PC)∶n(CHOL)=1∶1的条件下,蛋黄卵磷脂脂质体的平均粒径为2.59μm,包封率为(17.02±0.21)%,在37℃经40 h温育后,平均粒径增加0.53μm,药物渗漏量为(0.18±0.01)mg/h。平均粒径和包封率均高于大豆卵磷脂脂质体及猪脑卵磷脂脂质体,平均粒径增加值低于大豆卵磷脂脂质体及猪脑卵磷脂脂质体,渗漏速度高于猪脑卵磷脂脂质体,但低于大豆卵磷脂脂质体。对比实验证明,蛋黄卵磷脂脂质体的载药性能较好。     

白藜芦醇纳米结构脂质载体的药剂学处方设计与优化

目的为制备白藜芦醇纳米结构脂质载体,对其药剂学处方进行设计与优化。方法采用乳化蒸发-低温固化法制备白藜芦醇纳米结构脂质载体混悬液,考察了了载体用量、模型药物用量、固液脂质比以及表面活性剂等药剂学处方条件对白藜芦醇纳米结构脂质载体粒径与包封率的影响。结果确定了白藜芦醇纳米结构脂质载体最佳处方条件:单硬脂酸甘油酯80 mg,油酸20 mg,白藜芦醇10 mg,大豆卵磷脂12.5 mg,在此条件下制备的白藜芦醇纳米结构脂质载体微平均粒径为(104.2±5.1)nm,平均分布为0.184±0.021,包封率为(85.43±0.89)%。结论白藜芦醇纳米结构脂质载体包封率、粒度达到药典关于纳米粒子的质量相关要求。     

正交设计优化尼莫地平脂质体的制备工艺

优化了尼莫地平脂质体的制备工艺。利用乙醇注入法制备尼莫地平脂质体,以包封率为评价指标,采用正交试验优化制备工艺,并考察脂质体形态、粒径、Zeta电位和包封率。结果表明:优化工艺条件为药物-磷脂的质量比1∶20,胆固醇-磷脂的质量比1∶10,脱氧胆酸钠-磷脂的质量比1∶10,磷脂浓度1%;尼莫地平脂质体外观接近球形,平均粒径(122.8±5.3)nm,平均Zeta电位(-23.69±1.24)m V,包封率84.27%±0.58%。结论:优选得到的尼莫地平脂质体制备工艺合理,为尼莫地平新制剂的研发提供依据。     

盐酸二甲双胍脂质体最佳工艺条件的探索

目的:制备盐酸二甲双胍脂质体,采用反透析法测定其包封率,确定盐酸二甲双胍脂质体最佳工艺条件。方法:采用薄膜分散-超声法制备盐酸二甲双胍脂质体,以紫外分光光度法为分析手段,采用反透析法测定盐酸二甲双胍脂质体的包封率。结果:制备的脂质体包封率为53.76±0.76%(n=5)。结论:大豆卵磷脂与胆固醇最佳比例为8︰2,吐温-80最佳浓度为0.4%,最佳超声时间为5 min,水浴温度为40℃,透析时间5 h,脂质体包封率较高。     

苄达赖氨酸脂质体的制备

以苄达赖氨酸、大豆卵磷脂、胆固醇为原料制备了苄达赖氨酸脂质体。以包封率为主要指标,选取药脂比、超声时间、水相pH值和孵育温度4个因素进行正交实验优化制备工艺,用紫外分光光度计测定包封率,用粒度和Zeta电位分析仪测定所制备脂质体的粒径分布及Zeta电位。确定最佳制备工艺条件为:药脂比1∶5(g∶g)、超声时间15min、水相pH值5、孵育温度60℃,在该条件下所制得的3批苄达赖氨酸脂质体的平均包封率为81.54%,平均粒径为(99.85±9.60)nm,平均Zeta电位为(-30.6±1.8)mV,体外释放实验证明释放速度慢于市售制剂。表明所制备的苄达赖氨酸脂质体包封率高、稳定性好。     

紫甘薯花青素脂质体制备工艺的优化

以大豆卵磷脂、胆固醇为膜材,采用逆相蒸发法制备紫甘薯花青素脂质体,以凝胶柱层析法测定脂质体中紫甘薯花青素的包封率,得出制备紫甘薯花青素脂质体的最优工艺条件为:胆固醇与大豆卵磷脂物质的量比为1∶2,紫甘薯花青素水溶液(0.250 mg·m L-1)与乙醚的体积比为1∶4,逆相蒸发时间为30min,上述条件制备的脂质体平均包封率为76.61%。     

化妆品用原花青素脂质体的制备及应用性能研究

采用逆相蒸发法制备了化妆品用的原花青素脂质体,考察了原花青素与卵磷脂的质量比(药脂比)、聚乙二醇(PEG1500)的用量对脂质体稳定性和包封率的影响。实验发现,随着药脂比或PEG 1500用量的增加,脂质体的包封率均呈先增加后降低的趋势。在m(原花青素)∶m(卵磷脂)=1∶20,m(卵磷脂)∶m(PEG 1500)=3∶1的较优条件下,得到的原花青素脂质体的包封率为77.28%,平均粒径为144.9 nm,透射电镜下观察其外观为球形或椭球形。同时研究了最优条件下原花青素脂质体的保湿性能,实验证明原花青素脂质体的保湿性能明显优于游离的原花青素溶液。     

α-细辛脑前体脂质体制备工艺的研究

研究了α-细辛脑前体脂质体的制备工艺。采用载体沉积法制备α-细辛脑前体脂质体,单因素考察和正交试验设计法优选处方,超滤法结合高效液相法测定脂质体包封率。结果表明:最佳工艺为卵磷脂用量为2.0 g,胆固醇与卵磷脂的重比为1∶3,甘露醇与卵磷脂重比为3∶1,α-细辛脑与卵磷脂重比为1∶30,包封率为97.41%±1.05%。运用载体沉积法制备α-细辛脑前体脂质体,优化了前体脂质体制备工艺。     

低毒白藜芦醇脂质体的制备及其抗氧化活性研究

采用低毒的乙醇为溶剂,通过薄膜法制备低毒白藜芦醇脂质体,考察胆固醇与白藜芦醇质量比、胆固醇与卵磷脂质量比、PBS缓冲溶液的pH值,结合包封率、试剂用量和脂质体稳定性,确定白藜芦醇脂质体的最佳制备条件为:胆固醇∶卵磷脂=1∶3,胆固醇∶白藜芦醇=2∶1,PBS的pH值为7.4,白藜芦醇的包封率为84%。采用邻二氮菲-Fe2+氧化法测定脂质体的抗氧化活性,结果表明该脂质体清除自由基的能力高于白藜芦醇。     

南极冰藻DNA光修复酶脂质体的制备及其质量评价

以包封率为评价指标,氯仿-乙醚混合溶剂(2∶3,体积比)为有机相,固态大豆卵磷脂和胆固醇为膜材,采用逆向蒸发法制备南极冰藻DNA光修复酶脂质体。经单因素实验和正交实验确定光修复酶脂质体的最佳制备工艺条件为:膜材比3∶1、药脂比1∶10、油相与水相体积比4∶1、超声时间6min,在此条件下,光修复酶脂质体的平均包封率达到(44.13±2.90)%。所制得的光修复酶脂质体呈圆形或椭圆形,平均粒径为(490.9±2.3)nm,Zeta电位在-30~-60mV范围内,制剂的质量标准符合中国药典(2015版)要求,为DNA光修复酶在日用防晒品中的应用提供了可靠的理论依据。     

New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC–SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC–PLA particles prepared by classical method were used as comparison. The formulated MMC–SPC–PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA–MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA–MMC–SPC nanoparticles, and 74.1% for PLA–MMC particles. The IR analysis of MMC–SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.     

Preparation of PEGylated liposomes of docetaxel using supercritical fluid technology

The aims of this investigation were to develop a procedure to prepare and characterize docetaxel encapsulated PEGylated liposomes using supercritical carbon dioxide as antisolvent and optimize the process and formulation variables using response surface methodology. The process and formulation variables were optimized by “Box Behnken Design (BBD)” of response surface methodology (RSM) with temperature, pressure and CO₂ flow rate as independent variables and particle size and yield as dependent variables for process variables while the amount of hydrogenated soya phosphotidylcholine (HSPC), soya phosphotidylcholine (SPC) and cholesterol as independent variables and % entrapment efficiency as dependent variables for optimization of formulation variables. The optimized liposomal formulation was characterized for particle size, shape, morphology, crystallinity, zeta potential, % entrapment efficiency, residual solvent content and in vitro drug release. The process and formulation variables were optimized to achieve maximum drug entrapment efficiency and yield. Results for particle size, zeta potential, % entrapment efficiency and in vitro drug release of PEGylated liposomes were found to be 269.2 ± 2.8 nm, −27.2 ± 1.8 mV, 79.2 ± 4.4 %w/w and 37.5 ± 4.5% in 24 h, respectively. The liposomes were found to be small, unilamellar and spherical with smooth surface as seen in photomicrographs of scanning electron microscopy and transmission electron microscopy. Differential scanning calorimetry and X-ray diffraction results indicated a molecular dispersion of docetaxel in the liposomes. In this study, supercritical fluid technology was successfully used to prepare small, spherical and unilamellar liposomes of docetaxel with high entrapment. It was observed that supercritical fluid technique can be an excellent technique for preparation of docetaxel liposomes which otherwise is very difficult to prepare as a solvent free and stable liposomes.     

水杨酸壳聚糖/卵磷脂纳米粒的制备

采用溶剂注入法制备水杨酸壳聚糖/卵磷脂纳米粒。考察了粒子结构、形貌特征及表面电位等性能,并探讨了制备工艺对药物包封率的影响。确定最佳制备工艺为:卵磷脂质量浓度20 g/L、卵磷脂与壳聚糖及水杨酸与载体的质量比分别为3∶1和1∶6、水相pH=4。所制备的水杨酸壳聚糖/卵磷脂固体纳米粒子为球形粒子、表面电位+18.7 mV、包封率及载药量可分别达到55%和8.07%。     

β-桉油醇脂质体的超临界CO_2沉析法制备与理化性质测定

为提高β-桉油醇的生物利用度与肝靶向性,将其包封为脂质体。利用超临界CO2沉析技术,将脂质体膜材与β-桉油醇制成脂质体混悬液,再经真空干燥,制备了冻干β-桉油醇脂质体,并对脂质体形态、粒径、包封率、载药量、稳定性等各项理化参数进行测定与表征。考察了超临界CO2压力、温度、共溶剂乙醇在CO2中摩尔分数[x(CH3CH2OH)]等因素对脂质体制备的影响,在压力为30MPa,温度为338K、x(CH3CH2OH)=15%条件下,脂质体包封率为87.2%,载药量为5.9%,平均粒径为448.5nm。所制备的冻干β-桉油醇脂质体具有良好的复水性能,包封率、溶出度、稳定性等理化性质均符合中国药典的规定,为β-桉油醇的肝靶向药物开发提供了固体制剂中间体。     

芦丁脂质体的制备与药物包封率的测定

采用薄膜分散法,制备包封率高、粒径均匀、稳定性好的芦丁脂质体,并建立芦丁脂质体中芦丁含量和包封率的测定方法。以包封率为主要指标,通过正交设计优化芦丁脂质体的制备工艺,同时采用反相高效液相色谱法进行芦丁含量和包封率测定。结果表明,薄膜分散法制备的脂质体平均包封率为66.50%,外观均匀、稳定性良好。建立的反相高效液相色谱法能将芦丁与辅料分离良好,芦丁浓度在4～40μg/L范围内与峰面积呈现良好的线性关系（r=0.999 2,n=5）,平均回收率为99.0%,可用于测定芦丁脂质体的药物含量与包封率。     

α-硫辛酸脂质体的制备及质量评价

以大豆磷脂和胆固醇为膜材,采用薄膜-超声乳化分散法制备了α-硫辛酸脂质体。研究了配方中不同组分的比例对包封率的影响,并对脂质体的结构和形态、稳定性、表面电位、存贮条件进行了考察。结果表明,在大豆磷脂、胆固醇、α-硫辛酸的质量比为5∶1.5∶0.08时,制备的脂质体包封率为80.9%。该方法制备的α-硫辛酸脂质体为球形的单室结构,平均粒径为237 nm左右,表面电位为负,脂质体乳液的pH=6.5,适宜的贮存条件是3～5℃冰箱冷藏。     

Preparation a core-shell lipid/polymer nanoparticle containing Isotretinoin drug with pH sensitive property: A response surface methodology study

In this study, a core-shell lipid/polymer nanoparticle (NP) was prepared to deliver Isotretinoin drug with pH sensitive and controllable drug release property for oral administration usage. Chitosan was cross-linked to tripolyphosphate to form the core of the NP using the ionic gelation technique and coated with glycerol monostearate lipid as a shell by applying a two-step approach. Response surface methodology was used to investigate the effects of various parameters on particle size and drug entrapment efficiency of the nanoparticles. Optimal nanoparticles with lower particle size and higher entrapment efficiency had a diameter of 100 nm based on TEM analysis and 64% drug entrapment efficiency. Coating NPs surface with lipid changed the NPs charge, hydrophilicity and swelling property. Lipid coating NPs changed release rate from 6 to 4% after 2 h in simulated gastric fluid (SGF), 9 to 16% after 6 h in simulated intestine fluid (SIF) and 21 to 71% after 7 days in blood medium. Kinetic modeling of drug release confirmed Fickian diffusion based on Higuchi model in SIF and blood media where swelling and dissolution of polymer network were negligible, while drug dissolution due to polymer swelling in SGF media was the dominant mechanism for drug release.     

乙醇注入法制备司帕沙星脂质体

制备司帕沙星脂质体,单因素考察优化了制备工艺和处方,以提高脂质体的包封率.采用乙醇注入-高压均质法制备了司帕沙星脂质体,以透析-高效液相色谱法测定了含量和包封率.实验结果表明,司帕沙星脂质体的平均粒径为22.1 nm,包封率为47%左右.乙醇注入-高压均质法适用于制备司帕沙星脂质体,透析-高效液相色谱法操作简单、准确、重复性好,可用于测定司帕沙星脂质体的含量和包封率.     

微通道内载紫杉醇固体脂质纳米粒制备及工艺优化

目的:制备载紫杉醇固体脂质纳米粒。方法:微通道内采用溶剂扩散法制备脂质纳米粒,并通过正交优化制备工艺。结果:制备的纳米粒稳定性良好,平均粒径为(129.87±2.91)nm,包封率为(3.11±0.06)%,载药率为(43.67±0.24)%。结论:本研究制备的载药固体脂质纳米粒载药特性与重复性良好。