阿魏酸脂质体的处方筛选及体外释放实验

目的对阿魏酸(FA)脂质体进行处方筛选及体外释放实验。方法筛选制备FA脂质体的方法,并以磷脂比、药脂比、水化温度、PBS的p H为单因素考察指标通过正交实验筛选最优处方。采用透析袋法进行体外释放实验。结果采用薄膜分散法制备脂质体的粒径和PDI最好,最优处方为磷脂比为4︰1,药脂比为1︰20,PBS的p H为6.6。FA脂质体在8 h累积释放为46.11%。结论 FA脂质体具有一定的缓释作用。     

格列齐特脂质体的制备及质量评价

采用薄膜分散法制备格列齐特脂质体,以粒径和包封率为考核指标,通过单因素实验和正交实验优化制备条件,测定最优条件制备格列齐特脂质体的平均粒径和包封率。确定最优制备条件为:药脂比1∶10(g∶g)、超声时间10min、成膜温度60℃、缓冲液pH值6。所制备脂质体的平均粒径为(108.3±12.4)nm、包封率为(72.19±3.6)%、平均Zeta电位为(-40.8±2.3)mV,且在4℃下保存稳定性好。电镜照片显示,所制备脂质体圆整度好、粒径均一、无粘连。表明采用薄膜分散法制备格列齐特脂质体工艺稳定,质量可控。     

光甘草定脂质体制备及其质量评价

以光甘草定为原料,采用复凝聚法制备光甘草定脂质体,以包封率和粒度为指标,采用正交试验设计优化光甘草定脂质体的制备工艺;并对光甘草定脂质体的粒径分布、体外释药特性和稳定性进行了研究。结果表明:光甘草定脂质体制备的最佳条件为卵磷脂与胆固醇质量比4:1、超声波乳化时间40 min、光甘草定-丙二醇液质量浓度8 g/L,此条件下制得的脂质体粒径分布均匀,粒径为0.1~1.2 μm的比例为84.67%,包封率和粒度综合评分可高达78以上。光甘草定脂质体前120 min的体外释药性优于光甘草定粉末,3个月时光甘草定质量分数仍达38.5%,保留率为96.25%。复凝聚法制备光甘草定脂质体工艺简单,产品稳定性好。     

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。     

洛伐他汀长循环脂质体的制备及性质研究

目的:研制洛伐他汀长循环脂质体,考察其制备的影响因素,优化处方工艺,并对其理化性质和释放行为进行表征。方法:以PEG2000作为表面修饰剂,采用薄膜分散法制备了洛伐他汀长循环脂质体。采用微柱离心法测定包封率并结合粒径,在单因素考察的基础上,通过正交设计对处方和工艺进行优化,确定了洛伐他汀长循环脂质体的最佳处方及制备工艺。结果:制得的洛伐他汀长循环脂质体外观圆整,大小均一,可清晰看到指纹状结构,较普通脂质体更为不规则,平均粒径为(115.6±0.3 nm),Zeta电位为(-14.41±0.57 m V),载药量为(100±2.9 g/m L),包封率80%以上。用透析法考察了洛伐他汀长循环脂质体的体外释药行为,结果表明洛伐他汀长循环脂质体释放稍快于普通脂质体。     

脱氧氟尿苷脂质体的制备

目的建立脱氧氟尿苷(DFUR)脂质体的制备工艺。方法采用逆向蒸发法制备DFUR脂质体,并以包封率为参考指标,进行正交试验优化该脂质体的配方。以优化的配方制备脂质体,观察其微观形态,测定粒径、包封率及稳定性,并进行体外释药实验。结果制备DFUR脂质体的最佳配方为:卵磷脂/胆固醇(摩尔比)为2∶1,有机相/水相(体积比)为5∶1,DFUR浓度为2mg/ml,磷酸盐缓冲液pH值为7.0。以此配方制备,脂质体包封率可达52.15%。3批DFUR混悬液,粒径小于220nm的粒子比率均在70%以上,显微镜下观察可见,脂质体呈球形或椭圆形,粒径范围在0.15μm～1.00μm之间。4℃保存49d,脂质体的稳定性良好。其累积释放率远低于原料药浓度。结论已建立了DFUR脂质体的制备工艺,该工艺操作简便可靠,所需设备简单,稳定性较好,可用于包埋水溶性药物。     

复方石杉碱甲-虾青素脂质体的制备及评价

采用薄膜分散-探头超声法制备复方石杉碱甲-虾青素脂质体,高效液相色谱法分别测定石杉碱甲、虾青素的含量,葡聚糖凝胶柱色谱法分离脂质体与未包封的游离药,以包封率为指标,采用单因素考察和正交试验法优化脂质体制备工艺,并对其粒径、多分散系数(PDI)和形态进行综合评价。结果显示工艺验证复方脂质体中石杉碱甲平均包封率为65.35%±1.30%,虾青素平均包封率为50.42%±2.77%。粒径(156.22±3.71)nm, PDI为0.24±0.02,脂质体的粒径均一﹑包封率高﹑稳定性良好。     

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。     

抗坏血酸脂质体的制备与稳定性研究

以磷脂和胆固醇为膜材,采用薄膜分散-高压均质法制备抗坏血酸脂质体。通过对制得的脂质体进行表征考察后发现,平均粒径为90.8 nm,多分散指数(PDI)为0.231,包封率可达60%以上。将脂质体在室温和4°C条件下放置存储,以抗坏血酸脂质体的粒径和包封率变化为指标考察其稳定性。结果表明,4°C条件保存的脂质体粒径和包封率无明显变化,抗坏血酸脂质体稳定性良好。     

薄膜分散法制备SN-38脂质体及质量评价

为了制备7-乙基-10-羟基喜树碱（SN-38）脂质体并进行相关制剂学评价，采用薄膜分散法制备SN-38脂质体，以包封率为评价指标，用高效液相色谱法进行测定，通过单因素实验考察优化SN-38脂质体的制备工艺并进行质量评价。结果表明：制备工艺中，磷脂浓度3%，药脂比为1∶20，胆固醇与磷脂比为1∶6，水化温度为50℃，包封率平均值为92.0%，选择质量分数为10%的甘露醇为冻干保护剂，制备SN-38脂质体的冻干品；质量评价方面，SN-38脂质体的外观澄清带有蓝色乳光，平均粒径为147 nm。选用载体成膜法制备SN-38脂质体的工艺操作简便、合理可行。     

脂质体的制备,检测及其在化妆品中的应用研究

脂质体是目前医药界与化妆品界的研究热点之一,它是一种生物载体,加载活性成分的脂质体对治疗疾病与皮肤护理都非常有效。我们采用高压均质技术制备出符合粒径要求的脂质体,并用负染及冰冻蚀刻－电子显微镜法证明了脂质体的存在,从颗粒度和显微结构着手研究了它的稳定性,并测出它对水溶性物质的包封率,最终把脂质体应用于化妆品中。     

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。     

维生素A神经酰胺脂质体的初步研究

采用神经酰胺为类脂质材料研制维生素A脂质体，通过提高维生素A的稳定性和透皮吸收以有助于其在化妆品中的应用。筛选优化了维生素A脂质体的制备工艺，通过高效液相色谱对包封率、载药量、粒径及形态结构进行了研究。结果显示，脂质体形态较为圆整，平均粒径为O．171μm，包封率达98．5％，载药量为2．0％。神经酰胺作为类脂质材料制得的维生素A脂质体包封率高，可较好地应用于化妆品中。     

冻干茶多酚脂质体的制备及其质量

目的制备冻干茶多酚脂质体,并进行质量评价。方法采用不同种类及浓度的冻干保护剂制备冻干茶多酚脂质体,检测其包封率和有效粒径,筛选最佳冻干保护剂及其最适浓度,并对冻干茶多酚脂质体的形态、结构、粒径分布、Zeta电位和稳定性等性质进行观察。结果最佳冻干保护剂为15%(w/v)的蔗糖。所制备的冻干茶多酚脂质体再分散性良好;呈圆球形或椭球形,结构为大单室脂质体;有效粒径为(170.4±3.7)nm;Zeta电位为-60.5mV;在4℃条件下稳定性良好。结论已成功制备冻干茶多酚脂质体,其各项质量指标良好。     

Retention of Eucalyptol,a Natural Volatile Insecticide,in Delivery Systems Based on Hydroxypropyl‐β‐Cyclodextrin and Liposomes

Eucalyptol (Euc) is a natural monoterpene with insecticide effects. Being highly volatile and sensitive to ambient conditions, its encapsulation would enlarge its application. Euc‐loaded conventional liposomes (CL), cyclodextrin/drug inclusion complex, and drug‐in‐cyclodextrin‐in‐liposomes (DCL) are prepared to protect Euc from degradation, reduce its evaporation, and provide its controlled release. The liposomal suspension is freeze‐dried using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as cryoprotectant. The liposomes are characterized before and after freeze‐drying. The effect of Euc on the fluidity of liposomal membrane is also examined. A release study of Euc from delivery systems, in powder and reconstituted forms, is performed by multiple head extraction at 60 °C after 6 months of storage at 4 °C. CL and DCL suspensions are homogeneous, show nanometric vesicles size, spherical shape, and negative surface charge before and after freeze‐drying. Moreover, HP‐β‐CD does not affect the fluidity of liposomes. CL formulations present a weak encapsulation for Euc. The loading capacity of eucalyptol in DCL is 38 times higher than that in CL formulation. In addition, freeze‐dried DCL and HP‐β‐CD/Euc inclusion complex show a higher retention of eucalyptol than CL delivery system. Both carrier systems HP‐β‐CD/Euc and Euc‐loaded DCL decrease Euc evaporation and improve its retention. Practical Applications: Eucalyptol is a natural insecticide. It is highly volatile and poorly soluble in water. To enlarge its application, its encapsulation in three delivery systems (conventional liposomes, cyclodextrin/drug inclusion complex, combined system composed of cyclodextrin inclusion complex and liposome) is studied. In this paper it is proved that cyclodextrin/eucalyptol inclusion complex and eucalyptol‐in‐cyclodextrin‐in‐liposome are effective delivery systems for encalyptol encapsulation, retention, and release.     

Development and Characterization of DOPEPEG2000 Coated Oleic Acid Liposomes Encapsulating Anticancer Drugs

Liposomes have been widely investigated as drug carriers for a broad range of anticancer drugs. However, their application as a drug delivery system may be challenging due to low encapsulation of active ingredient and poor stability which leads to uncontrolled delivery of bioactive ingredients. The present study aims at incorporating 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamide‐N‐[methoxy(polyethylene glycol)‐2000 (DOPEPEG2000) into oleic acid (OA) liposomes in order to prolong the lifetime in blood circulation. The pH transition curve of oleic was obtained by titration of sodium oleate solution with 0.05 mol dm^?3 HCl to determine the region where liposomes were abundantly present. The critical vesicle concentration (CVC) was then determined by surface tension measurements. Dry lipid liposomes were hydrated with phosphate buffer at just over twice the CVC value. Optical polarizing microscopy (OPM) showed the presence of liposomes while transmission electron microscopy (TEM) confirmed that the liposomes prepared were spherical in shape and less than 200 nm in size. The incorporation of DOPEPEG2000 into the oleic acid liposomes reduced the average particle size and zeta potential to mimic the red blood cells. The encapsulation efficiency of various anticancer drugs was more than 60% while more than 20% of the drugs were released after 24 h. The results suggest that DOPEPEG2000: oleic acid at a molar ratio of 1:50 fulfilled the requirements for intravenous drug delivery.     

乳液聚合法包覆酞菁蓝的制备及性能研究

在超细可聚合分散剂/酞菁蓝分散体中添加共聚单体和引发剂,采用乳液聚合法对酞菁蓝进行包覆。考察了共聚单体结构及用量、引发剂用量、反应温度和时间对包覆酞菁蓝性能的影响。结果表明,与甲基丙烯酸甲酯(MMA)和丙烯酸丁酯(BA)相比,苯乙烯(St)是较佳的包覆共聚单体,当St质量为颜料质量的20%,过硫酸铵(APS)质量为St与烯丙氧基壬基苯氧基丙醇聚氧乙烯磺酸铵(ANPS)总质量的1.0%,于70～80℃反应2 h时,所制备包覆酞菁蓝的粒径较小,稳定性较高。与未聚合分散体相比,包覆酞菁蓝的耐热稳定性、耐酸碱稳定性和离心稳定性均有明显提高,FTIR和TEM照片表明,酞菁蓝表面包覆了聚合物,且包覆酞菁蓝粒度分布更均匀。