Ce(Ⅳ)盐引发丙烯腈在交联聚乙烯醇微球表面的接枝聚合

以戊二醛为交联剂,在反相悬浮体系中采用直接交联反应成球的方法,制备了聚乙烯醇(PVA)。以硫酸铈铵为引发剂,在酸性溶液聚合体系中实施了丙烯腈(AN)在交联微球CPVA表面的接枝聚合,制备了接枝微粒CPVA-g-PAN,考察了主要因素对交联成球反应与接枝聚合的影响规律。实验结果表明,在一定的搅拌速度下,分散剂用量及油水两相比是影响交联微球CPVA的主要因素。在Ce(Ⅳ)盐的氧化作用下,在含有大量羟基的CPVA微球表面会产生自由基,顺利地实现丙烯腈的自由基接枝聚合反应。反应温度、铈盐浓度和H+离子浓度是影响接枝聚合反应的主要因素。在适宜条件下,可制得PAN接枝度为27 g/100 g的接枝微球CPVA-g-PAN。     

CPVA微球表面接枝对羟基苯磺酸钠及其对茶碱的吸附研究

通过分子设计将2-氯乙基异氰酸酯(CIC)键合至聚乙烯醇微球(CPVA)表面制得CPVA-CIC,再将对羟基苯磺酸钠(HSS)固载于CPVA-CIC上制得功能微球CPVA-HSS。通过红外光谱(FI-TR)、扫描电子显微镜(SEM)及Zeta电位仪对功能微球进行表征,并考察主要因素对接枝微球固载量的影响,探索功能微球CPVA-HSS对茶碱分子的吸附性能及吸附机理。结果表明,通过CIC改性,阴离子单体HSS成功固载于基质CPVA表面,形成功能微球CPVA-HSS。CPVA-HSS对茶碱吸附5 h达到平衡,凭借其强的静电相互作用,pH5时在水溶液中吸附容量可达60 mg/g,随着温度的降低吸附量升高,而随介质盐度的增大吸附容量降低。功能微球的重复使用性较好。     

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。     

一种新型的负载蛋白质药物微球的制备和释药性能

为了制备具有蛋白药物结肠靶向释放性能的新型药物载体,采用了水相溶液滴定反应法,分别以牛血清白蛋白(BSA)和乳铁蛋白(LF)为模型蛋白质药物,制得壳聚糖/纤维素磷酸钠(NaCS)/三聚磷酸钠(TPP)载药微球。利用电镜SEM和显微镜观测拍照,对微球的表面和截面形貌进行了表征,发现微球球形规则且颗粒大小均一。同时进行了体外药物模拟释放试验,考察了载药微球先后经过模拟胃液、模拟小肠液和模拟结肠液时的释药性能,及不同的释放条件和制造条件对于微球释药性能的影响,尤其考察了不同蛋白药物和不同干燥方式的影响。结果表明由临界点干燥法制得的负载乳铁蛋白(LF)微球在模拟胃液和小肠液释放量中5 h内只释放出不到20%的蛋白药物,而后在结肠模拟液中4 h内释放出蛋白药物80%以上。这些结果表明,壳聚糖/NaCS/TPP体系具有一定的作为结肠靶向药物释放载体的应用潜力。     

Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS)

Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 μm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present.