星点设计法优化布南色林-泊洛沙姆温敏水凝胶处方及含量测定

目的 优化泊洛沙姆温敏水凝胶体系负载布南色林,并对凝胶中布南色林含量进行测定.方法 采用直接混合法配备含药温敏水凝胶体系,倒置小管法测定胶凝温度(Tgel).以Tgel为因变量,25％泊洛沙姆407体积(X1)、50％泊洛沙姆188体积(X2)和1％布南色林药物混悬液(X3)为考察因素,通过星点设计法优化制剂处方.采用...     

氟比洛芬阳离子脂质体温敏凝胶滴眼剂的眼部刺激性和药效学

目的制备氟比洛芬阳离子脂质体温敏凝胶滴眼剂(flurbiprofen cationic liposome thermo-sensitive hydrogel,FCLTH),考察其包封率、胶凝性质、眼部刺激性和药效作用。方法采用乙醇注入-超声法制备氟比洛芬阳离子脂质体,并对其包封率和理化性质等进行了测定。将氟比洛芬阳离子脂质体制备成温敏凝胶滴眼液,考察了FCLTH的胶凝行为、眼部刺激性和药效学。结果氟比洛芬阳离子脂质体包封率可达(84.9±2.75)%,zeta电位为(+33.4±9.68)mV,平均粒径(136±2.98)nm。FCLTH胶凝温度为31.9℃。眼部刺激性实验多次给药后,裂隙灯显微镜观察新西兰兔眼角膜无混浊,虹膜和结膜未见红肿、充血、肿胀等异常现象。组织病理学检查显示,新西兰兔眼7天多次给药后,与空白溶剂相比,给药组组织病理学改变无明显差异。药效学结果显示,FCLTH相对于氟比洛芬滴眼剂对新西兰兔眼急性炎症有抑制作用更强。结论采用乙醇注入-超声法制备的氟比洛芬阳离子脂质体有较高的包封率,且FCLTH在眼部温度下自发形成凝胶,无眼部刺激性,并能够有效抑制眼部炎症作用。     

Visualized intravesical floating hydrogel encapsulating vaporized perfluoropentane for controlled drug release

Intravesical drug delivery is the main strategy for the treatment of bladder disorders. To reduce the relief arising from frequent intravesical instillation, mucoadhesive hydrogel was used for the controlled release of the drug. However, the viscosity of mucoadhesive gel might cause severe urinary obstruction and bladder irritation. To solve all these problems, a floating hydrogel delivery system was developed using perfluoropentane (PFP) as the floating agent. After intravesical instillation of the floating hydrogel, the increased temperature in bladder vaporized PFP, resulting in the generation of microbubbles in the hydrogel. Then, it can float in urine to avoid the urinary obstruction and bladder irritation. In this study, systematic experiments were conducted to investigate the influences of PFP vaporization on the morphology and floating ability of hydrogels. The floating process is much milder and safer than other floating methods published before. In addition, PFP had been used as contrast agent, which affiliated the monitoring of gels during the operation. Therefore, this new drug delivery system addresses the problems of conventional intravesical instillation and is promising for clinic use.     

甲壳素温敏水凝胶止血作用的研究

目的 评价甲壳素温敏水凝胶的止血作用。方法 制作大鼠肝脏损伤出血模型,分为空白对照组、阳性对照组、实验组,空白对照组肝脏出血创面不使用止血材料,阳性对照组、实验组肝脏出血创面分别使用纤维蛋白粘合剂和甲壳素温敏水凝胶止血,记录出血时间和出血量,于术后测定血清中TGF-β1和IL-6的含量,观察肝脏愈合情况,对损伤肝脏进行组织学观察。结果 在手术中使用甲壳素温敏水凝胶能够快速止血,大鼠术后血清中TGF-β1和IL-6含量适中,在愈合过程中炎症反应轻。     

高效液相色谱-电喷雾源-质谱联用法测定紫杉醇热敏脂质体及其大鼠体内药动学研究

 目的 建立测定大鼠血浆中紫杉醇的高效液相色谱-电喷雾源-质谱联用（LC-MS/MS）方法,并进行大鼠体内药动学研究。方法 血浆经NaHCO₃溶液（pH 8.0）碱化后,用叔丁基甲醚提取。液相分离采用Zorbax SB C₁₈（2.1 mm×50 mm,3.5 μm）分析柱,柱温25 ℃,以甲醇-水（含0.5 mmol·L^-1乙酸铵）（70∶30,V/V）为流动相,流速为0.3 mL·min^-1,进样量5 μL;采用四级杆质谱检测器,电喷雾源（ESI）,正离子方式检测,在选择离子监测（SIM）模式下检测离子对m/z 876.3→308.1（紫杉醇）和m/z 830.2→549.2（多西他赛）。两组SD大鼠分别尾静脉推注7 mg·kg^-1紫杉醇热敏脂质体与紫杉醇注射液,采集血样后采用高效液相色谱-电喷雾源-质谱联用法测定血药浓度,计算主要药物动力学参数。结果 血浆中无干扰测定的内源性物质,每个样品的分析时间为3.5 min;紫杉醇在2~1 000 ng·mL^-1内呈良好的线性关系（r>0.998 5）,定量限为2 ng·mL^-1,日内、日间精密度RSD均小于15%。紫杉醇热敏脂质体的t_1/2β、MRT、AUC和CL与紫杉醇注射液均具有显著性差异。结论 本方法操作简便,特异性强,灵敏度高,可用于紫杉醇的药动学研究。与紫杉醇注射液相比,紫杉醇热敏脂质体能控制药物的释放,在一定程度上减轻了急性毒性,提高机体耐受性。     

快速凝胶化温敏型壳聚糖/甘油磷酸盐凝胶及释药性能

目的研究一种快速凝胶化壳聚糖/甘油磷酸盐（CS/GPS）凝胶及其温敏、释药性能。方法研究不同浓度的壳聚糖和甘油磷酸钠、混合溶液的pH值等因素对CS/GPS溶液凝胶化性能的影响。黏度法表征CS/GPS的溶胶-凝胶转变。以在37℃形成凝胶的体系负载模型药物扑尔敏的释药性能。结果壳聚糖和甘油磷酸钠浓度越大、溶液pH值越高,CS/GPS溶液在5min内凝胶化的温度越低,37℃时凝胶化速度越快。当pH值为7.3、浓度为21wt%的CS/GPS（质量比1∶18）的溶液升温至37℃,可在4min内凝胶化。黏度法表明在较低温度时,CS/GPS体系的黏度几乎无变化,当温度达到35℃时,体系黏度开始迅速增加,到36.5℃时,体系黏度已达到1911pa·s。药物释放实验表明,该凝胶对药物可持续释放9d以上。结论增大甘油磷酸钠的浓度和提高溶液的pH值,可得到在37℃下快速凝胶化的CS/GPS凝胶。该凝胶具有温敏性,形成的凝胶对药物具有缓释性。     

壳聚糖/β-甘油磷酸钠引导骨再生膜的制备及表征

目的：制备壳聚糖温敏凝胶引导骨再生屏障膜并进行结构表征。方法：通过分子自组装技术,合成含不同比例β-甘油磷酸钠的壳聚糖温敏凝胶,在37℃条件下干燥成膜。通过傅里叶红外光谱分析、X-射线衍射分析、扫描电镜分析对膜的结构进行表征并测量膜的拉伸强度。结果：壳聚糖温敏凝胶溶液在37℃条件下快速凝胶、脱水后成膜。红外光谱与X-射线衍射分析,壳聚糖与β-甘油磷酸钠之间产生了化学键结合;扫描电镜观察,膜具有多孔的表面结构和内部结构;β-甘油磷酸钠的含量越高,膜的孔径越大,拉伸强度有所降低,拉伸强度为0.78～1.13MPa。结论：壳聚糖温敏凝胶膜的制备条件温和、方法简便,其结构特征和力学性能符合可吸收引导骨组织再生膜的要求。     

A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel

The aim of this study was to investigate the suitability of poly-(d,l-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymer as a matrix material for a sustained-release system for docetaxel (DTX). The copolymers were synthesized by ring-opening polymerization reaction and characterized by ¹H-NMR and gel permeation chromatography. The DTX-loaded formulations were prepared, characterized. And the antitumor efficacy and the pharmacokinetics of DTX-loaded copolymer on A-549 lung tumor-bearing BALB/cA mice were investigated. The results showed that DTX-loaded copolymer highly increased the solubility of DTX by more than 3000-fold. And copolymer concentration as well as drug loading level exerted appreciable influence on the drug release behavior. Further, the pharmacokinetic test showed that DTX-loaded copolymer could be with the sustained-release nature for over 3 weeks, which correlated well with the in vitro release. Additionally, one intratumoral injection of the thermo-sensitive hydrogel containing DTX was comparable to three intravenous injections of DTX injection in inhibiting the tumor growth in A-549 lung tumor-bearing BALB/cA mice with a less toxic manner. PLGA-PEG-PLGA could thus provide a promising alternate locally delivered vehicle for DTX to achieve prolonged exposure having greater efficacy in inhibiting tumor growth with lower toxicity.