Microemulsion-based delivery of triamcinolone acetonide to posterior segment of eye using chitosan and butter oil as permeation enhancer: an in vitro and in vivo investigation

The aim of the study was to formulate a microemulsion (ME) using chitosan (CH) and the butter oil (BO) as a permeation enhancer for targeting drug to the posterior segment of the eye, via topical route. Triamcinolone acetonide (TA) was selected as the model drug since it undergoes extensive first-pass metabolism, leading to poor oral bioavailability of 23%. For optimisation of BO concentration, different ratios of TA:BO were prepared by simple physical mixing in the ratio of 1:9 to 9:1 and diffusion study was performed. MEs containing TA, TA:BO and TA CH ME were formulated by water titration method. Globule sizes of TA ME, TA:BO ME and TA CH ME were found to be 66.06?±?0.32?nm, 78.52?±?1.50?nm and 97.30?±?2.50?nm, respectively. In ex vivo diffusion studies using goats eye, TA:BO ME (31.33?±?0.46 and 33.98?±?0.23) and TA CH ME (24.10?±?0.41 and 27.00?±?0.18) showed higher percentage of drug diffusion in comparison to TA ME (13.29?±?0.41and 15.56?±?0.34) and TA solution (8.20?±?1.04 and 10.39?±?0.22) in presence and in absence of vitreous humour. Fluorescence intensity of coumarin-6 (as a marker) loaded ME with BO and CH was found to be higher, confirming their role in altering membrane permeability and facilitating coumarin-6 diffusion to the posterior chamber. Overall, it was concluded that BO enhances the bioavailability of TA across the retina, thereby proving its potential as permeation enhancer in facilitating drug delivery to the posterior segment of the eye.     

川芪眼用微乳原位凝胶的流变学及释放动力学分析

目的:研究考察川芪眼用微乳原位凝胶的流变学及释放动力学行为,为该制剂的后续研究与开发提供参考。方法:使用MCR 102型流变仪考察川芪眼用微乳原位凝胶的流体性质及线性粘弹区域。体外释放度采用改良Franz扩散池法,以半透膜为释放膜,川芎嗪、藁本内酯为指标成分,取样时间点分别为0.5,1,2,4,6,8 h。结果:川芪眼用微乳原位凝胶是一种假塑性流体并存在线性粘弹区域。以剪切力为指标,确定的线性粘弹区域为0~302.74 Pa,以形变为指标得到的线性粘弹区域范围为0~7.45%。在临界点时,其储能模量(G')等于损耗模量(G″),均为2 976.60 Pa;临界剪切力为302.74 Pa;临界形变7.45%。8 h内6份样品中川芎嗪的平均累积释放量33.71μg,平均累积释放率90.08%,释放动力学遵循Higuchi方程。8 h内6份样品中藁本内酯平均累积释放量为68.46μg,平均累积释放率为84.32%,其释放动力学遵循零级动力学方程。结论:川芪眼用微乳原位凝胶具有较好的粘弹性,并在一定范围内可以发生可逆形变。川芎嗪释放动力学是川芎嗪的理化性质与基质骨架共同作用的结果,藁本内酯的释放动力学主要受其理化性质的影响。     

Mn2+掺杂普鲁士蓝纳米颗粒T1-T2双模磁共振成像和光热治疗的体外研究

目的 制备一种Mn²⁺掺杂普鲁士蓝纳米颗粒,用于检测体外T1-T2双模磁共振成像和光热治疗效果。方法 采用微乳液法,以二氯化锰、氯化亚铁和铁氰化钾为原料制备Mn²⁺掺杂普鲁士蓝纳米颗粒;观察纳米颗粒的体外T1-T2双模磁共振成像性能;考察808 nm 激光照射后纳米颗粒的升温效果;通过CCK-8法和AM/PI活死细胞染色法观察体外光热治疗效果。结果 成功制备了Mn²⁺掺杂普鲁士蓝纳米颗粒,粒径为39.46±0.42 nm,电位为-25.9±1.2 mV,粒径均匀,分散性好;808 nm激光照射10 min 后,纳米颗粒分散系可以升温至 90 ℃。由 7T 磁共振测得的数据拟合获得 r1 值为 0.68（mmol/L）^-1s^-1,r2 值为 3.65（mmol/L）^-1s^-1,具有良好的T1-T2双模磁共振成像效果;在808 nm激光照射下,可显著降低细胞存活率（P<0.05）;CCK-8 法和AM/PI活死细胞染色法的结果均显示纳米颗粒对HepG2细胞具有良好的光热治疗效果。结论 成功制备了粒径均一的Mn²⁺掺杂普鲁士蓝纳米颗粒,该纳米颗粒的T1-T2双模磁共振成像效果和体外光热治疗效果良好,且无明显细胞毒性。     

多发性硬化患者血浆溶血磷脂类分子水平及其临床意义

目的：观察多发性硬化（MS）患者血浆中溶血磷脂酸（LPA）和酸性磷脂（AP）以及血清超敏C反应蛋白（Hs‐CRP）水平的变化,探讨这些炎性标志物与MS疾病活动程度的关系。方法选取14例急性期MS患者、15例缓解期MS患者及30名健康体检者,测定其血LPA、AP和 Hs‐CRP的水平变化。结果（1）急性期MS组治疗前血浆 LPA、AP和血清 Hs‐CRP水平均显著高于缓解期 MS组（P＜0.01）和健康对照组（P＜0.01）。（2）急性期MS组经治疗28 d后血浆LPA、AP和血清Hs‐CRP水平显著低于治疗前（P＜0.01）。（3）急性期MS组治疗前血浆LPA与AP水平存在相关性（r＝0.807,P＜0.01）,急性期MS组治疗前血浆LPA和AP与血清Hs‐CRP水平存在相关性（r＝0.574,P＜0.05;r＝0.776,P＜0.01）。结论血浆LPA、AP和血清 Hs‐CRP水平可能作为MS患者疾病活动性的炎性标志物。     

熊果酸磷脂复合物纳米结构脂质载体的制备及其体内药动学研究

目的制备熊果酸磷脂复合物纳米结构脂质载体,并考察其体内药动学。方法乳化?超声分散法制备熊果酸磷脂复合物纳米结构脂质载体,测定粒径、Zeta电位、包封率、载药量、体外释药。大鼠灌胃给药(12.5 mg/mL)后,于0.25、0.75、1、1.5、2、2.5、3、4、6、8、12 h采血,HPLC法测定熊果酸血药浓度,计算主要药动学参数。结果所得制剂呈类球形或球形,平均粒径、Zeta电位、包封率、载药量分别为(209.32±4.47)nm、-(10.82±0.42)mV、80.54%、3.57%;36 h内累积释放度低于70%,释药符合Weibull模型(R2=0.9906)。与原料药、磷脂复合物比较,纳米结构脂质载体tmax延长(P<0.05,P<0.01),Cmax、AUC0~t、AUC0~∞升高(P<0.01);与原料药比较,磷脂复合物、纳米结构脂质载体相对生物利用度分别增加至2.73、3.95倍。结论磷脂复合物纳米结构脂质载体可促进熊果酸体内吸收,提高其口服生物利用度。     

单纯形网格法优化外用中药不同油水分配系数多成分微乳制剂处方

目的采用单纯形网格法优化中药不同油水分配系数(log P值)多成分微乳给药系统,并对其质量进行评价。方法通过饱和溶解度法筛选了表面活性剂、助表面活性剂及油相,并以蛇床子素、川芎嗪、阿魏酸、葛根素及京尼平苷为模型药代表中药复杂成分,在伪三元相图的基础上,应用单纯形网格法优化中药不同油水分配系数多成分微乳,以外观、粒径及多分散指数(PDI)为评价指标,通过Design Expert 8.06软件进行试验设计和模型构建,响应面数据分析优化和验证最佳处方组成。通过对微乳外观、稳定性及其粒径、Zeta电位等的测定对其进行质量评价。结果优化得到的最佳处方为油酸-Labrasol-丙二醇-水(5.303∶29.336∶7.334∶58.027),所形成的微乳外观澄清透明,流动性好,呈淡黄色,平均粒径为(118.77±3.37)nm,PDI为0.282±0.020,Zeta电位为(0.346±0.050)m V,稳定性良好。结论优化之后的中药不同油水分配系数多成分微乳性质稳定,载药量高;制备并优化了适宜于不同logP值(-1.01~3.85)成分的微乳载体,为此范围内的多成分中药提供可行的微乳载体,简化其前期微乳处方筛选工作。     

Effects of partial ileocolectomy and Crohn's disease on biliary lipid secretion

The effects of interruption of the enterohepatic circulation of bile acids on biliary lipid secretion have only been studied experimentally, and quantitative data in patients are lacking. Therefore, biliary lipid secretion during steady-state meal perfusion of the duodenum was studied in six patients with partial ileocolectomy, five patients with Crohn's disease, and five normal subjects. Bile acid outputs in the resection patients were significantly lower than in normal controls, (6.87±2.10 mmol/6 hr and 13.5±2.16, respectively;P<0.001) and were also decreased in two of the five Crohn's disease patients. Bile acid outputs in patients with resection progressively decreased in the course of the perfusion study; phospholipid and cholesterol secretion did not decrease to the same extent, and cholesterol saturation gradually increased. Bile of these patients, therefore, was frequently supersaturated due to uncoupling of bile acid secretion and outputs of the other biliary lipids. Bile acid outputs, although decreased, did not reach very low values, which shows that the enterohepatic circulation was not totally interrupted. Chenodeoxycholic acid was the main bile acid component of bile in patients with ileocolonic resection. Deoxycholic acid was absent from bile of four resected patients and two Crohn's patients. Two patients with active Crohn's disease had low bile acid outputs despite only moderate fecal bile acid losses. Therefore, decreased outputs may be caused by decreased bile acid pool not compensated for by increased bile acid synthesis in severely ill patients.     

益母草碱油包油微乳在小鼠体内组织分布研究

目的 探讨益母草碱油包油微乳剂和益母草碱混悬剂在动物体内药物代谢动力学特征和组织靶向性。方法 采用高效液相色谱法测定小鼠血浆与组织中益母草碱浓度,计算药物代谢动力学参数。结果 与混悬剂比较,益母草碱微乳剂在体内平均滞留时间提高了7 h,其相对生物利用度为550.684%;益母草碱微乳剂AUC(0→∞)在小鼠各组织的分布整体提高到混悬组的3.626~26.265倍;益母草碱微乳剂在心、肺和脑组织的靶向指标分别为1.044、1.335和4.772。结论 益母草碱油包油微乳提高了生物利用度,对脑组织具有较好的趋向性分布。