营养物质纳米运送系统的研究与应用

近年来纳米技术得到人们广泛关注,本文着重介绍了纳米技术在营养运送系统的应用,用于营养物质运送的纳米载体具有缓释,生物相容性以及生物可降解性等特点,可以提高营养物质的稳定性和生物利用度,具有很好的发展前景.     

7-Ethyl-10-hydroxycamptothecin proliposomes with a novel preparation method: optimized formulation,characterization and in-vivo evaluation

Context:?The proliposomes were used to solve the stability of the ordinary liposomes. Objective: 7-ethyl-10-hydroxycamptothecin (SN-38) proliposomes for intravenous (i.v.) administration were prepared successfully by a new method.

Materials and methods:?SN-38 liposomes solution was reconstituting automatically from proliposomes on contact with the acetic acid buffer solution (0.2 M, pH 2.6). The formulation was optimized by the Box–Behnken design. The physicochemical characteristics of the SN-38 proliposomes were studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The stability studies were also carried on. The FLU–HPLC system was served to study the concentration of SN-38 in the plasma of Sprague Dawley (SD) rats.

Results:?The optimized formulation was SN-38: 0.03 g; Soybean phospholipid (SP): 0.6 g; dextrose: 3.00 g. The entrapment efficiency of the optimized formulation was >85% and the mean particle size was about 231 nm. The stability studies showed that SN-38 proliposomes were stable in dark at 20–25°C for 6 months at least. The pharmacokinetic parameters of i.v. administration demonstrated that the half-life of SN-38 loaded in the liposomes was prolonged in vivo.

Discussion and conclusion:?The SN-38 proliposomes was prepared successful by the analysis of TEM, SEM, DSC and XRD, and SN-38 liposomes could be reconstituted on contact with the hydration medium. SN-38 liposomes circulated for a longer time in the blood circulating system than SN-38 solution, which contributed to maintaining the drug action.     

Preparation,Characterization, and Evaluation of Liposomal Ferulic Acid In Vitro and In Vivo

In the present study, various gradients were evaluated for efficient loading of weak acid into liposomes. Several salt gradients showed efficient loading of ferulic acid (FA) into liposomes and the optimized conditions were established in calcium acetate gradient method to obtain 80.2 ± 5.2% entrapment efficiency (EE). Unilamellar vesicles were observed in micrographs and liposomal FA showed good stability. 80% of FA was released from liposomes within 5 h in vitro. There is a novel finding in this study: that drugs could be entrapped with a high solubility in the intraliposomal buffer in contrast to the low solubility in the extraliposomal buffer. The results of body distribution in rats indicated that liposomes could improve the body distribution of FA. For FA liposome, the concentration of FA in brain was two-fold higher than that of free FA. Liposomal FA was a promising approach to improve the body distribution of FA.     

Physical characterization and cellular uptake of propylene glycol liposomes in vitro

In order to facilitate the intracellular delivery of therapeutic agents, a new type of liposomes–propylene glycol liposomes (PGL) were prepared, and their cell translocation capability in vitro was examined. PGL was composed of hydrogenated egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a model drug, characterization of loaded PGL were measured including surface morphology, particle size, elasticity, encapsulation efficiency of curcumin and physical stability. Using curcumin-loaded conventional liposomes as the control, the cell uptake capacity of loaded PGL was evaluated by detection the concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL exhibited such advantages as high encapsulation efficiency (92.74% ± 3.44%), small particle size (182.4?±?89.2?nm), high deformability (Elasticity index?=?48.6) and high stability both at normal temperature (about 25°C) and low temperature at 4°C. From cell experiment in vitro, PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution. Little toxic effect on cellular viability was observed by methyl tetrazolium assay. In conclusion, PGL might be developed as a promising intracellular delivery carrier for therapeutic agents.     

新型佐剂及其与重组HBsAg结合物的理化性质的研究

目的 制备一种新型正电荷脂质体免疫佐剂,研究其粒径、稳定性,及其与重组乙肝表面抗原的结合率和结合物的稳定性。方法 合成DC胆固醇(DC-Chol),并采用薄膜法制备脂质体,电镜测其粒径。脂质体与HBsAg混合后高速离心,用 ELISA分别测定游离和结合的 HBsAg含量,计算HBsAg与脂质体的结合率。将 DC-Chol与HBsAg结合物免疫BALB/c小鼠,检测其抗体的滴度。结果 合成DC-Chol的产率为67％,C、H、N含量与理论含量相比,在测量误差范围内。脂质体平均粒径180mm,4℃放置10个月约产生15％的沉淀。结合物明显沉淀,上清清亮,结合率在 98％左右。初次免疫 3周脂质体组的IgG1的 A值是铝佐剂组的 6倍,IgG 2a是 14.9倍。结论本法制备的脂质体粒径小,稳定性好,与HBsAg结合率高,能有效地促进体液免疫和细胞免疫,为制备新型乙肝疫苗打下基础。     

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。     

Tamoxifen-encapsulated vesicular systems: cytotoxicity evaluation in human epidermal keratinocyte cell line

Aim: Tamoxifen is a nonsteroidal estrogen receptor modulator indicated in the treatment of breast cancer. Apoptosis has been reported to be a major mechanism for its antitumor effect. Tamoxifen has also shown significant potential in treating various dermatological disorders including psoriasis, characterized by hyperproliferation of epidermal keratinocytes. An endeavor was made in the current studies to investigate the potency of vesicle-encapsulated tamoxifen on human epidermal keratinocyte cell lines. Methods: Drug was encapsulated in the phospholipid-based vesicular systems, namely, conventional liposomes and flexible-membrane liposomes. In vitro cytotoxicity evaluation of the formulations was carried out employing MTT cell proliferation assay. Results: A composition-dependent strong inhibition in the viability of epidermal keratinocyte cells was observed. Conclusion: The encouraging findings of this work construe immense potential of the tamoxifen-encapsulated vesicular systems in the management of psoriasis.     

薄膜蒸发-冷冻干燥法制备乳糖酶脂质体

以蛋黄卵磷脂和胆固醇为膜材,采用薄膜蒸发-冷冻干燥法制备乳糖酶脂质体。以包埋率为指标,通过单因素试验研究制备工艺,并研究其形态、粒径分布和红外光谱性质。最佳工艺参数为:蛋黄卵磷脂与胆固醇摩尔比为2︰1,乳糖酶的添加量为150 U,海藻糖与脂质质量比为4︰1,磷酸盐缓冲液pH6.8,包埋率可达到28%以上;乳糖酶脂质体在电镜下呈球状或近似球状的小囊泡;平均粒径为463.18±5.09 nm;红外光谱分析表明海藻糖可与脂质体磷脂C=O基团形成氢键。