微囊的制备方法研究进展

微囊是一种定向药物载体,属于靶向给药系统的一种新剂型,具有很大的开发应用价值。本文对微囊的制备方法进行总结,旨在为药物新剂型的开发提供一定的理论基础。     

正交实验法优选补骨脂微囊的制备工艺

目的 优选以乙基纤维素为囊材的补骨脂微囊的制备工艺.方法 采用液中干燥法制备补骨脂微囊.以包封率、载药量和微囊收得率为指标,通过正交实验考察囊芯和囊材的比例,乳化剂用量和不同乙基纤维素液与液体石蜡的比例对制备补骨脂微囊的影响.结果 优选出补骨脂微囊的最佳制备工艺为采用1％的乙基纤维素丙酮溶液作为囊材溶液,乙基纤维素溶液与液体石蜡比例为1:2,(V/V),芯材比例为1:1(W/W),以司盘-80为乳化剂,其用量为1％.结论 优选出的制备工艺可靠、简单可行,经验证其结果稳定、可靠.     

Gastroresistant microcapsules: new approaches for site-specific delivery of ketoprofen

Ketoprofen is a potent non-steroidal anti-inflammatory drug (NSAID) that has been widely used in the treatment of rheumatoid arthritis and other related conditions. However, it carries the risk of undesirable systemic side effects and gastrointestinal irritation at the usual dose of oral administration. The aim of this study was to prepare and evaluate gastroresistant microcapsules containing ketoprofen. Microcapsules were obtained by a spray-drying process starting from an O/A emulsion in the presence of different pH-dependent materials (Eudragit^® L100, Eudragit^® S100, and stearic acid) dissolved in the external phase. The influence of formulation factors (oily phase employed for drug solubilization, type of coating) on the morphology, particle size distribution, drug loading capacity, in-vitro release, and ex-vivo permeation characteristics were investigated. Drug loading capacity was very high for all the microcapsules prepared. Formulation factors did not significatively influence the mean particle size, but modified microcapsule in-vitro and ex-vivo behavior.     

微囊化成骨细胞诱导骨髓间充质干细胞体外成骨分化的量效研究

目的探讨微囊化成骨细胞体系细胞添加量对诱导骨髓间充质干细胞体外成骨分化的影响。方法制备含有成骨细胞的海藻酸钠-聚赖氨酸-海藻酸钠微囊,与间充质干细胞的共培养,在1,7,14 d通过细胞增殖量、碱性磷酸酶活性、实时定量PCR等检测,统计结果并分析。结果各时段细胞增量无统计学意义;碱性磷酸酶活性随细胞浓度增加表现出递增趋势,且骨钙蛋白mRNA的表达结果基本一致。结论微囊化成骨细胞在低浓度下已能促进骨髓间充质干细胞成骨分化,浓度升高时促分化能力越强,但达到一定浓度后继续提高时,对成骨分化的作用则不再增强。     

硫酸长春新碱PLGA微囊的制备及体外释放性质研究

目的:制备硫酸长春新碱乳酸-乙醇酸共聚物[Poly(lactide-co-glycolide),PLGA]微囊并考察其体外释放.方法:采用W/O/W复乳-溶剂挥干法制备硫酸长春新碱PLGA微囊,考察了内、外水相pH值,PLGA,Span 80,NaCl浓度和CH_2Cl_2挥干方法对微囊包封率的影响,并对其形态、粒径分布和体外释放性质进行了研究.结果:制得的硫酸长春新碱PLGA微囊为球形,表面光滑,平均粒径约为643.1 nm,平均包封率为39.5%.结论:采用复乳-溶剂挥干法成功制备硫酸长春新碱PLGA微囊,体外释放表明具有其缓释作用.     

酮康唑微囊对部分真菌的抑菌实验

目的　考察临床分离的几种致病真菌对酮康唑微囊的体外敏感性。方法　采用试管稀释法和琼脂稀释法进行体外药效学研究。结果　 2 1株念珠菌对酮康唑、酮康唑微囊、氟康唑片的MIC分别为 0 .0 2～ 2 .5、6 .2 5～ 10 0、0 .319～ 10 0 μg·ml-1;1株酵母菌对这 3种药物的MIC分别为 0 .0 8～ 0 .16、12 .5～ 2 5、2 5 μg·ml-1结论　酮康唑微囊具有一定的体外抗真菌活性。     

Potentiation of anticancer effects of microencapsulated carboplatin by hydroxypropyl α-cyclodextrin

Cyclodextrins are cyclic oligosaccharides that can change physicochemical properties of drugs by forming inclusion complexes with them. These changes may enhance the therapeutic potential of drugs by diminishing their decomposition before they enter tissues and by altering how they enter tissue. Carboplatin is an anticancer drug that is active against brain tumors and has recently been tested as a potential agent for interstitial chemotherapy. To test whether complex formulation with cyclodextrins would improve interstitial treatment with carboplatin, we studied the efficacy of carboplatin-cyclodextrin complexes, free and encapsulated, in an experimental rat glioma model. Carboplatin hydroxypropyl α-cyclodextrin complexes were incorporated into ethylcellulose microcapsules at a 2.2% w/w loading. We found that carboplatin was released from these microcapsules in a sustained manner for at least 110 days in vitro, that the rate was faster than that of encapsulated carboplatin alone, and that hydroxypropyl α-cyclodextrin protected the carboplatin from degradation. Further, the complex was more effective than carboplatin alone when tested on monolayers of F98 glioma cells. For testing the efficacy of the carboplatin-hydroxypropyl cyclodextrin complex in the rat glioma model, 56 Fischer rats were injected in the left hemisphere with F98 glioma cells. Five days later the rats were randomly divided into seven groups. Median survival of the first control group receiving no treatment was 20 days. The second group receiving an intratumoral injection of carboplatin had a median survival of 1 day, indicating severe cytotoxicity. The third group receiving systemic carboplatin had a median survival of 34 days. Median survival of the fourth group which received empty microcapsules was 24 days. The fifth group, treated with microcapsules loaded with hydroxypropyl α-cyclodextrin alone, showed a median survival of 20 days. The sixth group, treated with microcapsules loaded with carboplatin alone, showed a median survival of 34 days. The seventh group, treated with microcapsules loaded with carboplatin-hydroxypropyl α-cyclodextrin complex, showed a median survival of 51 days. This experiment demonstrated that the microencapsulated carboplatin-hydroxypropyl α-cyclodextrin complex is more effective than the nonencapsulated carboplatin. This study also shows that interstitial delivery of carboplatin-hydroxypropyl cyclodextrin complexes from a microencapsulated formulation is effective against experimental brain tumors.     

In vitro activation of human macrophages by alginate-polylysine microcapsules

Microencapsulated islets of Langerhans have been proposed as a bioartificial pancreas. However, foreign body reaction with fibrosis has been observed around implanted microcapsules. Since macrophages are present in this reaction and interleukin-1 (IL-1), a cytokine released by activated macrophages, may induce fibrosis, we tested the capacity of alginate-polylysine microcapsules to activate macrophages. Human monocytes were isolated from whole blood of healthy donors by a Ficoll density gradient and adherence to a plastic support. Monocytes were cultured for 24 h with: (1) alginate-polylysine microcapsules; (2) lipopolysaccharide (LPS) (positive control group); and (3) alone (negative control group). Monocyte activation was evaluated by measuring the secretion of IL-1β and the production of intracellular IL-1α and IL-1β. Macrophages characterization was performed by immunocytological subtyping. IL-1β release and intracellular IL-1β and IL-1β production were significantly higher when macrophages were cultured with alginate-polylysine microcapsules than when macrophages were cultured alone. In conclusion, macrophages are activated in vitro by alginate-polylysine microcapsules. This effect may be involved in the fibrosis observed in vivo around implanted microcapsules. In addition, interleukin-1, released during macrophage activation, may cross the microcapsule membrane and impair islet function.     

Silk fibroin layer-by-layer microcapsules for localized gene delivery

Herein, we describe the delivery of plasmid DNA (pDNA) using silk fibroin (SF) layer-by-layer assembled microcapsules. Deposition of fluorescently labeled SF onto polystyrene (PS) template particles resulted in increasing fluorescence intensity and decreasing surface charge in correlation to SF layer number. After removal of the PS core, hollow, monodisperse, and structurally stable SF microcapsules of variable size and shell thickness were obtained. Plasmid DNA encoding for enhanced green fluorescent protein (eGFP) was loaded onto 1 or 4 μm capsules, either by incorporation of pDNA within the innermost layer of the shell or by adsorption to the microcapsules surface, and in vitro pDNA release, cytotoxicty and eGFP expression were studied. Sustained pDNA release over 3 days was observed using both loading techniques, being accelerated in the presence of protease. DNA loaded SF microcapsules resulted in efficient cell transfection along with low cytotoxicity after 3 days incubation compared to treatment with pDNA/branched polyethylenimine complexes. Among the tested conditions highest transfection efficiencies were achieved using 1 μm capsules where pDNA was adsorbed to the capsule surface. Our results suggest that SF microcapsules are suitable for the localized delivery of pDNA, combining low cytotoxicity and high transfection efficiency.