葛根素前体脂质体的制备及体外性质研究

 目的制备葛根素前体脂质体,并对其体外性质进行研究。方法采用载体沉积法制备葛根素前体脂质体,单因素考察和正交实验优选处方;透射电镜观察形态;马尔文激光粒度仪测定粒径、Zeta电位;透析法结合高效液相色谱法测定包封率;动态透析法考察体外释药性质。结果制得的脂质体形态多为圆形或椭圆形,平均粒径为278nm,Zeta电位为-17.5mV,包封率为(43.53±1.33)%,体外释药符合一级动力学方程。结论葛根素前体脂质体包封率较高,具有一定的缓释效果。     

薄膜分散法制备白藜芦醇长循环热敏前体脂质体及其表征研究

目的:对白藜芦醇长循环热敏前体脂质体制备的研究以及对其性质进行分析。方法:先用薄膜分散法制备白藜芦醇长循环热敏脂质体后,再用冷冻干燥法来制备白藜芦醇长循环热敏脂质体的前体。采用电势测定仪、HPLC等方法对该脂质体的包封率、粒径、稳定性、载药量、电位、释放度等来展开系统的检查。结果:白藜芦醇长循环热敏前体脂质体水合后形成白藜芦醇长循环热敏脂质体,粒径均值为(107.9±3.6)nm,Zeta电位的均值为(-12.2±1.6)m V,包封率可达89.4%;该脂质体在相变温度42℃下药物释放达到94%以上。结论:采用长循环热敏来制备的白藜芦醇前体脂质体含量与包封率检查方法准确、快速、简单且方法简便易行。载药量大,包封率好,工艺比较稳定。本实验可为新型白藜芦醇静脉注射用热敏脂质体的研究提供基础。     

药物载体空白脂质体前体的制备及性质的研究

以蛋黄卵磷脂、胆固醇为膜材,加入适量的高分子表面活性剂,选择合适的支持剂,采用冷冻干燥法制备了空白脂质体前体,并用它作为药物载体,将药物溶液分散在载体中,制成药物脂质体．研究了空白脂质体前体的再分散性及物理稳定性．空白脂质体前体再分散性良好,平均粒径为０．７５μｍ,粒径分布比较集中,在室温下贮存７个月、９个月后再分散其平均粒径分别为０８１μｍ、０８４μｍ,对５ Ｆｕ的包裹率也没有发生显著改变。用５ Ｆｕ,阿霉素（ＡＤＭ）等为模型药物,考察了影响药物脂质体包裹率的因素,并将最优条件固定．研究结果表明：空白脂质体水相的ｐＨ值、离子强度、再分散药物溶液的浓度（即药物与磷脂的重量比）对药物包裹率有显著影响．     

The pharmacokinetics of methotrexate after intravenous administration of methotrexate-loaded proliposomes to rats

The pharmacokinetics and tissue distribution of methotrexate (MTX) were investigated after intravenous (i.v.) injection of free MTX (treatment I), MTX-loaded proliposomes (treatment II), and empty proliposomes mixed manually with free MTX (treatment III), 8 mg kg^?1, to rats using an HPLC assay. After i.v. infusion in 1 min, the plasma concentration of MTX (C_p), the area under the plasma concentration-time curve (AUC, 639 versus 913 μg min mL^?1), the terminal half-life (t_1/2, 48.8 versus 397 min), the mean residence time (MRT, 8.40 versus 325 min), and the apparent volume of distribution at steady state (V_ss, 98.1 versus 2800 mL kg^?1) were significantly higher; however, the total body clearance (CL, 12.5 versus 8.76 mL min^?1 kg^?1), renal clearance (CL_R, 4.49 versus 2.78 mL min^?1 kg^?1), non-renal clearance (CL_NR, 7.50 versus 5.99 mL min^?1kg^?1), and the amount of MTX excreted in urine (X_u, 808 versus 685 μg, p < 0.0948) were significantly lower from treatment II than from treatment I. This could be due to the fact that some of the MTX-loaded liposomes (formed immediately after hydration of MTX-loaded proliposomes) are entrapped in tissues and the rest are present in the plasma (higher MRT and V_ss from treatment II), and MTX is slowly released from MTX-loaded liposomes (higher t_1/2 from treatment II). In the present HPLC assay, the concentrations of MTX represent the sum of free MTX and MTX loaded in liposomes (higher C_p and AUC, slower CL from treatment II). After i.v. infusion in 1 min, some pharmacokinetic parameters, such as t_1/2, MRT, and V_ss, were significantly different between treatments I and III; however, the differences seemed to be smaller than those between treatments I and II. After 30 min from i.v. infusion, the tissue to plasma (T/P) ratios of MTX in kidney and stomach from treatment II were significantly lower than those from treatment I. This suggested that the i.v. administration of MTX-loaded proliposomes might have fewer side effects in the organs than that of free MTX. The mean amount of MTX loaded in MTX-loaded proliposomes was 2.54 mg/g proliposomes and the MTX was released slowly from hydrated MTX-loaded proliposomes when incubated with phosphate-buffered saline (PBS), rat plasma, or rat liver homogenate.     

葛根素前体脂质体的质量考察

目的:制备葛根素前体脂质体,并对制剂质量进行考察。方法:采用山梨醇载体沉积法制备葛根素前体脂质体,并对制剂的形态学、包封率、粒径分布、体外释药、稳定性等性质进行考察。结果:本实验制备的脂质体形态多为圆形或椭圆形,平均粒径为278nm,Zeta电位为-17.5mV,包封率为(43.5±1.3)%,体外释药符合一级动力学方程,常温放置稳定。结论:葛根素前体脂质体包封率较高,具有一定的缓释效果,稳定性较好。     

莪术油前体脂质体的制备及其质量评价

 目的制备莪术油前体脂质体,以期得到不良反应较小的莪术油新剂型。方法采用非水溶剂(叔丁醇-水共溶剂)冷冻干燥法制备莪术油前体脂质体,对莪术油脂质体的包封率、粒径、形态、Zeta电位、溶血性及体外释放速率进行考察。结果莪术油脂质体包封率为92.2%,平均粒径为457nm,Zeta电位为-23.6mV,48h后体外释放大于94.1%,无溶血性,稳定性好。结论采用叔丁醇-水共溶剂冷冻干燥法获得了高包封率、粒径均一、无溶血性、稳定的莪术油前体脂质体。     

槲皮素液体型前体脂质体的处方筛选及质量评价

目的:分析槲皮素液体型前体脂质体的处方影响因素并考察该制剂的质量。方法:采用液体型前体脂质体的制备方法制备槲皮素前体脂质体。以槲皮素脂质体的粒径和包封率为指标,通过单因素试验和正交试验筛选槲皮素脂质体的处方。利用Zetasizer 3000HS型粒径仪测定脂质体的粒径和Zeta电位。采用透析法分离槲皮素脂质体和游离槲皮素,通过HPLC测定槲皮素的含量,检测波长360 nm,流动相甲醇-0.1%甲酸水溶液(55∶45),考察该制剂在人工胃液和人工肠液中的稳定性。结果:选择卵磷脂为脂质膜材,聚氧乙烯氢化蓖麻油(cremophor RH40)为表面活性剂,药脂比1∶20,cremophor RH40按磷脂和主药总量的20%加入,制剂中槲皮素质量浓度10.0 g·L-1。该处方下前体脂质体水合后的粒径(228.7±2.61)nm,Zeta电位(-21.2±1.47)m V,包封率(93.12±1.18)%,有较好的重复性,且水合后脂质体在12 h内具有良好的稳定性,适合口服给药。结论:制备的槲皮素液体型前体脂质体具有良好体外性质。该制剂在人工胃液和人工肠液中的粒径略大于在水中的粒径,但无论是在哪种水性介质中,12 h内其粒径变化不显著。     

结肠定位壳聚糖包衣氟尿嘧啶脂质体的制备、形态与体外释放

目的探讨药物结肠定位壳聚糖包衣脂质体的制备、形态及其在体外释药特性。方法用罗丹明B异硫氰酸(RBITC)和Bodipy-PC分别标记壳聚糖和磷脂,用前体脂质体方法制备氟尿嘧啶脂质体,利用激光扫描共聚焦显微镜观察壳聚糖包衣脂质体的形态;考察壳聚糖包衣脂质体在人工胃液、人工肠液和人工结肠液中的释放。结果 脂质体包衣前后粒径分别为2.071和2.750 μm。壳聚糖能较好地包覆脂质体;3种脂质材料不同的包封率分别为99%,61%,72%。未包衣的脂质体在人工胃液中4 h已释放完全,而包衣脂质体在人工胃液4 h释放6.3%,在人工肠液中8 h仅释放6.8%,但在人工结肠液中释药明显加快,t1/2为3.63 h。结论结肠定位壳聚糖包衣脂质体制备可行,在人工结肠液中,体外释放符合Higuchi方程。     

AAPE proliposomes for topical atopic dermatitis treatment

Abstract

Context: Anti-inflammatory effect of advanced adipose stem cell derived protein extract (AAPE) could be improved by minimising protein degradation. Objective: To develop a proliposomal formulation of AAPE for the treatment of topical atopic dermatitis. Materials and methods: Proliposomal powder was manufactured by evaporating a solution of soy phosphatidyl choline, AAPE and Poloxamer 407 in ethanol under vacuum on sorbitol powder. Characterisation of proliposomes (zeta potential, diameter, stability and flowability) as well as in vivo efficacy in a dermatitis mouse model was investigated. Results and discussion: Reconstitution of the proliposomal powder formed liposomes of 589?±?3.6?nm diameter with zeta potential of ?51.33?±?0.36?mV. Protein stability was maintained up to 90 days at 25?°C as proliposomes. In vivo studies on atopic dermatitis mouse model showed a significant reduction in IgE levels after topical AAPE proliposome treatment. Conclusion: AAPE proliposomes maintained protein stability and showed promising results for atopic dermatitis treatment.     

重组L—门冬酰胺酶前体脂质体对急性淋巴白血病小鼠的治疗作用和毒性考察

目的考察重组L-门冬酰胺酶前体脂质体(L-ASNasePL)与重组L-门冬酰胺酶（L-Asparaginase,L-ASNase）对移植性小鼠急性淋巴白血病的作用,及相关急性毒性。方法采用DBA／2小鼠L1210腹水瘤模型,L-ASNasePL组和L-ASNase组小鼠每天腹腔注射一次,连续10d。另设L-ASNasePL组小鼠静脉注射给药,给以最大药物浓度（4000kU·m1