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。     

响应面法优化黑加仑花色苷脂质体制备工艺的研究

为降低花色苷的理化性质对其生理活性发挥的限制,以大豆卵磷脂和胆固醇为膜材料对花色苷进行包埋。采用薄膜-超声法制备花色苷脂质体。以包封率为考察指标,在单因素的基础上通过响应面法优化制备花色苷脂质体的生产工艺。最佳工艺为：制备温度48．80％、卵磷脂：胆固醇为1.79：1（mg/mg）、花色苷量0．12mg,在此条件下包封率可达74．54％。     

茶多酚脂质体的制备

利用响应面分析法(RSM)对乙醇注入-超声法制备茶多酚脂质体的工艺进行研究。在单因素试验基础上选取影响茶多酚脂质体包封率的4个主要因素茶多酚与磷脂质量比(TP:PC)、胆固醇与磷脂质量比(CH:PC)、VE与磷脂质量比(VE:PC)和乙醇用量,根据Box-Behnken试验设计原理采用四因素三水平的响应面分析法对各个因素的显著性和交互作用进行研究。茶多酚脂质体最佳制备工艺参数为TP:PC=81:300,CH:PC=58:300,VE:PC=16.7:300和乙醇4.5mL。在最优条件下茶多酚脂质体包封率达78.10%,电镜观察表明茶多酚脂质体形态均匀,呈现不规则的椭圆形,粒径分布于400～1000nm范围内。     

中链脂肪酸-VC复合脂质体制备及初步稳定性

以磷脂和胆固醇为膜材,脂溶性的中链脂肪酸(MCFAs)和水溶性的VC为模型药物,以脂质体的包封率和粒径为指标,分别采用薄膜法、复乳法、薄膜-高压法、复乳-高压法制备中链脂肪酸-VC复合脂质体,筛选出最佳制备方法(复乳-高压法),并通过单因素试验设计,确定复合脂质体的最优处方工艺为:总脂材质量浓度5.0g/100mL,MCFAs质量浓度10.0mg/mL,VC质量浓度3.0mg/mL,卵磷脂与胆固醇质量比为4:1,卵磷脂质量与无水乙醇体积比为1:10(g/mL),吐温与总脂材质量比为3:10,VE与卵磷脂质量比为4:100,120MPa条件下超微乳化处理2次。制备的复合脂质体MCFAs包封率达到49.01%,VC的包封率达到54.19%,平均粒径90.3nm,在4℃贮藏15d,包封率和粒径变化不大,表明脂质体低温贮藏稳定性良好。     

Positively and negatively charged liposomes as carriers for transdermal delivery of sumatriptan: in vitro characterization

Background: The influence of liposome composition, lamellarity, preparation method, and charge on the encapsulation efficiency, size, polydispersity, and surface charge of sumatriptan liposomes was studied. For this purpose, we studied multilamellar, unilamellar, and frozen and thawed liposomes. Positively or negatively charged liposomes were obtained using both phosphatidylcholine and cholesterol, in combination with stearylamine or dicetylphosphate. Liposomal formulations were characterized by confocal laser scanning microscopy and optical microscopy for vesicle formation, morphology, and lamellarity by dynamic laser light scattering for size distribution and polydispersity, and electrophoretic mobility for zeta potential determination. To obtain more information about the sumatriptan encapsulation, dynamic dialysis technique was employed. The sumatriptan amount was quantified by high-performance liquid chromatography. Results: Overall obtained results showed that liposomes may be interesting carriers for sumatriptan succinate. Statistical analysis evidenced that the preparation method does not affect the evaluated characterization parameters. However, the presence of charge inducer agents modified these characteristics. Highest loading efficiency of sumatriptan was exhibited for positively charged liposomes containing 6.58:10.34:3.73 mmolar ratio for phosphatidylcholine : cholesterol : stearylamine. The mean size was affected by the charge inducer, being smaller in positively charged liposomes. Logically, surface charge of liposomes varied as a function of the employed charged agent. Also, interesting results were obtained when vesicles were loaded with sumatriptan, showing a statistical significance between all pairs, comparing the formulations with and without drug. Conclusion: Results obtained revealed that the presence of sumatriptan into the vesicles has a different behavior in negatively and positively charged liposomes.     

Chitosan-Based Thermosensitive Hydrogel Containing Liposomes for Sustained Delivery of Cytarabine

Sustained release thermosensitive solution containing cytarabine-loaded liposome delivery system offers the possibility of reduced dosing frequency and sustained drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C-GP) thermosensitive solution having the property to gel at body temperature and to maintain its physical integrity for longer period of time was used. The C-GP solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the results showed that the cytarabine liposomes were capable of high encapsulation efficiency (85.2?±?2.58%) with the mean diameter of 220?±?6.9 nm of extruded cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed spherical-shaped liposomes after extrusion with smooth surface. In vitro studies of CGPCLL in PBS buffer showed that this system can sustain release of encapsulated drug for more than 60 h compared with drug-loaded liposomal suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher t_1/2 (28.86 h) and AUC 2526.88 μg/mL h compared with cytarabine-loaded liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats. CGPCLL was capable of sustaining the cytarabine release for more than 60 h in vivo compared with CLLS and CGPFC which showed maximum amount of drug release within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels at body temperature and can sustain the delivery of cytarabine effectively.     

脂质体体系中甲基紫精与抗坏血酸的光敏氧化还原

叶绿素a作为一种光敏色素嵌入脂质体的类脂双分子层液晶态膜中,光照时观察到脂质体外部水相中的甲基紫精被脂质体内部水相中的抗坏血酸还原。用来配制缓冲液的三羟甲基氨基甲烷同时可起质子载体作用。本文还初步讨论了pH值的改变对光敏反应的影响。     

O-palmitoylcurdlan sulfate (OPCurS)-coated liposomes for oral drug delivery

O-Palmitoylcurdlan sulfate (OPCurS) was applied to the liposomal surface to improve the stability of liposomes. To synthesize OPCurS, curdlan was chemically sulfated and then modified with a palmitoyl derivative. The synthesized OPCurS was characterized by Fourier transform-infrared spectroscopy (FT-IR). OPCurS-coated liposomes prepared by the solvent evaporation method were characterized for size, shape, surface charge, and stability in simulated gastric fluid (SGF) and sodium cholate solution. The sizes of OPCurS-coated liposomes increased with the OPCurS content of liposomes and zeta potential decreased when OPCurS was applied to the liposomal surface. With the increase in the content of OPCurS attached to the liposomal surface, the stability of liposomes in SGF and sodium cholate solution was gradually induced and the stability was most improved at a lipid/OPCurS weight ratio of 1.5. Liposomes not coated with OPCurS released 99.5+/-2.3% of the initial 5-carboxyfluorescein (5-CF) content, whereas OPCurS-coated liposomes released 53.7+/-3.7%. OPCurS on the surface of liposomes suppressed the release of 5-CF. Theses results indicate that OPCurS-coated liposomes can be effectively used as a drug delivery carrier via oral administration.     

Oxidation of cholesterol catalyzed by amyloid beta-peptide (Abeta)-Cu complex on lipid membrane

A catalytic reaction of H2O2 production by an amyloid beta-peptide (Abeta)-Cu complex with cholesterol incorporated in a liposome was kinetically analyzed. The Michaelis-Menten model was applied to the H2O2 production reaction using cholesterol as the substrate catalyzed by the Abeta-Cu complex. The Km value for the Abeta-Cu complex catalytic reaction with cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes (Km=0.436 microM for Abeta(1-40); Km=0.641 microM for Abeta(1-42)) was found to be smaller than that with cholesterol-containing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes (Km=0.585 microM for Abeta(1-40), Km=0.890 microM for Abeta(1-42)). The results imply that membrane properties could play an important role in the interactions of the Abeta-Cu complex with cholesterol in these liposomes. Considering the physical states of the cholesterol/POPC (liquid disordered phase) and cholesterol/DPPC (liquid ordered phase) liposomes in the present reaction conditions, the data obtained suggests that the H2O2-generating activity of the Abeta-Cu complex, accompanied by oxidation of membrane-incorporated cholesterol, could be effected by the phase of the liposome membranes.     

脂质体作为药物载体的研究进展

脂质体是磷脂分散在水中定向排列而形成的具有单层或复层膜结构的囊泡 ,它可以分别包封脂溶性和水溶性药物 ,其结构类似于生物膜 .以脂质体为载体制成的脂质体药物具有良好的靶向性 ,可以提高和延长药物疗效 ,缓和药物毒性 ,具有避免耐药性和改变给药途径等优点 .本文对脂质体药物的性能和制法等近年来的一些进展进行了综述 .