灯盏花素TPGS聚合物胶束的制备工艺研究

制备灯盏花素聚乙二醇1000维生素E琥珀酸酯聚合物(Bre/TPGS)脂质体,采用薄膜溶剂挥发法,以载药量、包封率、粒径为考察指标,通过单因素分析法研究反应条件对聚合物脂质体制备的影响,对药物与载体药物比为7:100(质量比)、水化时间为2 h、水化温度为37℃等因素,以L_9(3~3)正交设计试验,确定最佳反应条件。该脂质体制备工艺简单,其粒径、包封率、载药量均可控,并具有一定的缓释作用。     

维生素E脂质体的制备与性能研究

采用薄膜蒸发-高压均质法制备维生素E（VE）脂质体，研究了VE脂质体配方中不同成分的比例及水合介质对脂质体包封率的影响。结果表明，VE脂质体载药量越大，包封率越低。胆固醇含量在体系中要适当。最佳的水合介质是磷酸盐缓冲液。采用薄膜蒸发结合高压均质处理法制备的VE脂质体粒径达到120nm，而且比较稳定。     

超临界CO2快速膨胀制备鱼腥草挥发油脂质体

采用改进的超临界CO2快速膨胀方法制备了鱼腥草挥发油脂质体,并对其进行了表征. 考察了压力、温度、共溶剂乙醇用量等因素对脂质体制备的影响,在压力30 MPa、温度338 K及乙醇用量15%条件下,脂质体包封率为83.2%,载药量为5.2%,平均粒径为332.5 nm. 脂质体包封率、溶出度、稳定性等理化性质均符合中国药典的规定,载药量满足注射剂给药量的要求.     

盐酸伊立替康、二氢杨梅素复方脂质体的制备及其体外释放研究

目的:制备共载化疗药CPT-11及中药成分DMY的复方脂质体,对该脂质体进行质量检测,包括考察其外观形态、粒径分布、包封率、载药量等,并考察复方脂质体的体外释放能力。方法:用乙醇注入法-硫酸铵梯度法制备CPT-11-DMY复方脂质体,根据L9(34)正交试验优化药物处方,并加以验证;用紫外分光光度法测定包封率及载药量;利用动态透析法来分析CPT-11-DMY复方脂质体体外释放趋势。结果:正交实验得到的最优处方制备出的复方脂质体中CPT-11包封率为(82.58±1.48)%,载药量为(4.5±1.3)%,DMY包封率为(71.45±1.03)%,载药量为(5.7±1.1)%;平均粒径为(123.1±1.8)nm,PDI值为0.181,Zeta为(-24.3±0.51)mV;体外释放通过数学参数拟合结果表明,复方脂质体的释药行为符合weibull模型,24h内复方脂质体中CPT-11和DMY的累计释放率分别为(61.45±1.88)%和(72.67±1.07)%。结论:应用乙醇注入法结合硫酸铵梯度法成功制备复方脂质体,采用的方法简单可行,结果可靠,且包封率高。     

硫酸头孢喹肟脂质体的制备工艺

采用固体分散技术结合泡腾技术制备硫酸头孢喹肟脂质体,考察了减压旋转蒸发温度、氯仿用量、大豆卵磷脂/胆固醇质量比、吐温-80用量、药/脂质量比、柠檬酸与NaHCO3用量对脂质体外观形态和包封率的影响. 通过正交实验优化制备条件,并探讨了脂质体的形成机制. 结果表明,制备硫酸头孢喹肟脂质体的优化条件为：大豆卵磷脂/胆固醇/吐温-80/柠檬酸/NaHCO3的质量比为37:18:5:33:7,药/脂质量比1:10. 该条件下所制脂质体外观形态良好,粒径分布均匀,平均粒径为(203±5) nm,平均包封率为55.17%±0.44%,平均载药量为5.04%±0.02%.     

两亲性聚(甲基丙烯酸甲酯-co-甲基丙烯酸)胶束包覆维生素A

采用透析法制备了包覆维生素A的两亲性聚(甲基丙烯酸甲酯-co-甲基丙烯酸)[P(MMA-co-MAA)]胶束。对空白、载药聚合物胶束的粒径、Zeta电位、形貌进行了比较;考察维生素A加入量对包覆率和载药量的影响;考察包覆前后维生素A的贮藏稳定性;并对维生素A包覆胶束模拟缓释进行了研究。结果表明:数均摩尔质量为64 886 g·mol-1、单体摩尔比为7∶3的双亲性无规聚合物P(MMA-co-MAA)在0.1 mol·L-1硼砂缓冲液(pH=9.2)中的临界胶束浓度(cmc)为0.050 g·L-1;包覆维生素A的胶束粒径比空白胶束增大近1倍,Zeta电位变得更负;当维生素A加入量为包覆材料的15%时,包封率和载药量分别达到81.9%和13.5%;包覆后的维生素A在光照60 d后保留率仍能达到56.3%,而维生素A在自然光照下的半衰期仅为15 d,有效延长了维生素A的贮存时间;载药胶束在接近皮肤表面pH的磷酸盐缓冲液(pH=5.0)中10 h内稳定释放76.1%的维生素A,可应用于化妆品中。     

5-氟尿嘧啶明胶微球的制备、表征及释药性能

为了获得粒径为50～100μm的5-氟尿嘧啶／明胶微球（5-Fu／GMs），采用乳化一化学交联法，讨论了5-Fu用量、乳化剂浓度和水／油比等因素对微球平均粒径、载药量及包封率等的影响。结果表明，5-Fu／明胶质量比为0．5，乳化剂浓度为0．5％和水／油相体积比为1／10时，可获得最大的载药量30．1％和包封率90．2％。体外释药性能表明5-氟尿嘧啶明胶微球具有明显的药物缓释作用。     

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。     

维生素C脂质体的制备与研究

采用改进薄膜法制备维生素C脂质体，以卵磷脂：胆固醇=6：1制成空白脂质体，以空白脂质体：维生素C=9：2，超声处理3min，并经稳定化处理后得到维生素C脂质体，包封率最高可达18．09％；电子显微镜下观察结果显示产品为单室脂质体，粒径集中在20～50nm之间；低温贮存环境有利于脂质体的稳定。     

神经酰胺脂质体——含角质层脂质膜的脂质体

角质层的渗透屏障大多是由饱和脂质如神经酰胺、胆固醇和游离脂肪酸组成。它是物质交换的有效阻隔并防止皮肤干燥。神经酰胺脂质体(Cerasomes)是一种脂质体,它的膜是由最重要的角质层脂质组成的。神经酰胺脂质体作为类皮肤膜的来源,它能加快受损屏障层的再生、降低皮肤刺激,并且它还提供了将角质层脂质应用于化妆品中简单而有效的途径。     

响应面法优化西兰花种子萝卜硫素前体脂质体的制备工艺

将萝卜硫素制成前体脂质体以提高萝卜硫素的稳定性,改善其水溶性和生物利用度。以包封率和粒径为指标,分别考察了载体材料、表面活性剂种类和用量及脂药比的影响,响应面法优化得前体脂质体的最优处方。通过常温稳定性实验考察了脂质体和前体脂质体的稳定性。结果表明,最优处方为脂药比为6.5:1,NaCl与萝卜硫素质量比为105:1,泊洛沙姆-188与药物质量比为1.5:1。得最大平均包封率为77.43%,平均粒径为160.5 nm。稳定性实验表明,以药物保留率为指标时,脂质体与前体脂质体在60天内稳定性好且萝卜硫素的保留率高。以包封率为指标时,脂质体混悬液产生沉淀,包封率降低,前体脂质体在60天内包封率无明显降低。表明前体脂质体可解决萝卜硫素的氧化变质和脂质体因沉淀、絮凝等原因而造成的包封率降低。前体脂质体包封率高,制备简单,不仅提高了萝卜硫素的稳定性,且可提高萝卜硫素的水溶性,应用前景广阔。     

Preparation of liposomes entrapping essential oil from Atractylodes macrocephala Koidz by modified RESS technique

A modified technique of rapid expansion of supercritical solutions (RESS) was applied to incorporate essential oil extracted from Atractylodes macrocephala Koidz into liposomes. In the modified RESS process, both the liposomal materials and the essential oil were dissolved in the mixture of supercritical carbon dioxide (SC-CO₂)/ethanol and then the solution was sprayed into an aqueous medium through a coaxial nozzle to form liposomes suspension. The encapsulation performance of liposomes could be controlled by changing expansion processing conditions such as pressure, temperature of SC-CO₂ and the amount of ethanol. The entrapment efficiency, drug loading and average particle size of liposomes were found to be 82.18%, 5.18% and 173 nm, respectively, under the optimum conditions of at a pressure of 30 MPa, a temperature of 338 K and a ethanol mole fraction in SC-CO₂ [(x(CH₃CH₂OH)] of 15%. The formed liposomes appeared as double-layered colloidal spheres with a uniform and narrow particle size distribution. The physicochemical properties of liposomes including entrapment efficiency, dissolution rate and stability were complied with the provisions of Chinese pharmacopoeia. All these results indicate that the modified RESS technique is an innovative way for self-assembly of liposomes incorporation of multi-components extracted from Chinese traditional medicines in the SC-CO₂.     

SOD—GC脂质体的制备及包封率的测定

半乳糖神经酰胺（Galactosyl ceramide,简称GC）是一种制备脂质体的新材料,性质稳定,具独特的护肤作用,以GC为主要膜材,用乙醇注入法制备包含有超氧化物歧化酶的脂质体（SOD-GC脂质体）;用SOD蛋白含量法和SOD活性法测定包封率,经正交法优化选择,最佳制备条件为膜脂量1.0mg/mL、SOD量0.1mg/mL,缓冲液pH5.8,此时包土率可达35.68%,两种包封率测定方法结果相近,可以相互参照,这种SOD-GC脂质体有望在护肝肤品和皮肤外用药物治疗等方面应用。     

含多重结构包覆载体技术的研究进展

概述了多重结构乳状液的结构类型、制备方法及其在药品、化妆品等领域的应用,综述了含多重结构的包覆载体,包括了脂质体、微胶囊和固体脂质纳米粒及其制备方法与研究现状,阐述了含多重结构的包覆载体的特性。     

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。     

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.     

维生素C和水杨酸复合脂质体制备及影响因素的研究

以大豆磷脂为膜材,采用复乳-超声法制备同时含有脂溶性水杨酸和水溶性维生素C的复合脂质体。研究配方中不同成分的质量比、维生素C水溶液的pH、乳化温度、包衣等对脂质体包封率和稳定性的影响。结果表明,在m(大豆磷脂)∶m(胆固醇)∶m(水杨酸)∶m(维生素C)=4∶1∶0.75∶1,维生素C水溶液的pH为5,初乳和复乳化温度分别为25、45℃时制备的复合脂质体中维生素C和水杨酸的包封率分别为48.2%和55.4%;包衣处理使水杨酸/维生素C复合脂质体稳定性提高。     

Inhibiting the vascular smooth muscle cells proliferation by EPC and DPPC liposomes encapsulated magnolol

Percutaneous transluminal coronary angioplasty (PTCA) is a non-surgical modality for treating stennosis. However, the recurrence of restenosis in 30-50% patients within 6 months is the major drawback of PTCA. The major reason of restenosis is the proliferation of the vascular smooth muscle cells (VSMCs). Magnolol, a pure compound extracted from Magnolia officinalis, encapsulated by liposome was investigated for inhibiting the VSMCs proliferation leading to restenosis by PTCA. 1,2-Diacyl-Sn-glycero-3-phosphocholine (EPC) and 1,2-dipalmitoyl-Sn-glycero-3-phosphocholine (DPPC) liposomes were utilized to encapsulate the magnolol. EPC liposome obtained the higher encapsulation efficiency than DPPC lipsomes from UV-vis spectroscopy study. The inhibiting efficiency of EPC and DPPC liposomes encapsulated magnolol was higher than pure magnonol. Magnolol encapsulated by EPC liposomes had better efficiency on inhibiting VSMCs than DPPC liposome. Addition of cholesterol in liposomes could slightly enhance the encapsulation efficiency. The particles sizer analysis revealed the average particles size of EPC and DPPC liposomes encapsulated magnolol became larger than pure EPC or DPPC liposomes. From the transmission electron microscopy (TEM) analysis, the magnolol seems to interfere with EPC and DPPC liposomes to form a homogeneous lipid bilayer.     

Preparation and characterization of SLNs (W/O/W type) contained lipoic acid PEG ester by variation lipid

This study describes a nanoparticle preparation method using SLNs (solid lipid nanoparticles: W/O/W type). Classical methods have high encapsulation efficiency for hydrophobic drugs but have low encapsulation efficiency (2–3%) for hydrophilic drugs. The preparation of SLNs that has a far higher skin penetration effect compared with general liposomes is proposed in this study. An additional aim is to also maximally increase encapsulation efficiency of hydrophilic drugs. The SLNs preparation method described here used coconut oil, jojoba oil and macadamia oil that are resistant to degradation by microorganisms and are usable emulsifiers due to their physical properties imparted by their fatty acid composition. The results indicate that SLNs containing coconut oil had the highest encapsulation efficiency and also the smallest average particle size (270 nm). The largest particle size was produced by macadamia oil and 1% Tween 60. The fastest release of contents resulted from SLNs made of coconut oil and 2% Tween 60, while the slowest release was from SLNs made of macadamia oil and 2% Tween 20.     

The pH-Dependent Controlled Release of Encapsulated Vitamin B1 from Liposomal Nanocarrier

In this work, we firstly presented a simple encapsulation method to prepare thiamine hydrochloride (vitamin B₁)-loaded asolectin-based liposomes with average hydrodynamic diameter of ca. 225 and 245 nm under physiological and acidic conditions, respectively. In addition to the optimization of the sonication and magnetic stirring times used for size regulation, the effect of the concentrations of both asolectin carrier and initial vitamin B₁ on the entrapment efficiency (EE %) was also investigated. Thermoanalytical measurements clearly demonstrated that after the successful encapsulation, only weak interactions were discovered between the carriers and the drug molecules. Moreover, the dissolution profiles under physiological (pH = 7.40) and gastric conditions (pH = 1.50) were also registered and the release profiles of our liposomal B₁ system were compared with the dissolution profile of the pure drug solution and a manufactured tablet containing thiamin hydrochloride as active ingredient. The release curves were evaluated by nonlinear fitting of six different kinetic models. The best goodness of fit, where the correlation coefficients in the case of all three systems were larger than 0.98, was reached by application of the well-known second-order kinetic model. Based on the evaluation, it was estimated that our liposomal nanocarrier system shows 4.5-fold and 1.5-fold larger drug retention compared to the unpackaged vitamin B₁ under physiological conditions and in artificial gastric juice, respectively.