Exploring the utility of the Chasing Principle:influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol(CAR), cinnarizine(CIN) or R3040 on drug solubilization in a twocompartment in vitro lipolysis model. Correlation of drug log P or solubility in SNEDDS with drug solubilization during in vitro lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1(1:1, w/w) and Kolliphor RH40, with ethanol at 10%(w/w) were used. SNEDDS were named F65, F55 and F20(numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS(F0) were also analyzed. While the ranking order of drug solubilization was F65? F55? F204F0 for CAR; F65? F554F204F0 for CIN and F65? F55? F204F0 for R3040-with higher CAR solubilization than for R3040 and CIN-the ranking of S_(eq)of CAR, CIN and R3040 in SNEDDS was F65 o F55o F20, F65? F554F20 and F654F554F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high S_(eq) in SNEDDS did not reflect high drug solubilization. As CAR(log P 3.8) showed higher solubilization than CIN(log P 5.8) and R3040(log P 10.4), a correlation between drug log P and drug solubilization was observed.

两种苦参碱自纳米乳化制剂大鼠在体三重单向肠淋巴通道转运研究

目的对比研究2种不同苦参碱自纳米乳化制剂肠淋巴转运差异。方法采用大鼠三重在体单向肠灌流(T-SPIP)实验,以苦参碱原药为参比,利用乳糜流动阻断剂(秋水仙碱),对比研究2种不同苦参碱自纳米乳化制剂在大鼠不同肠段淋巴吸收特性的差异。结果自乳化制剂粒径小且分布均匀,在大鼠的不同肠段均有较高吸收,苦参碱磷脂复合物自纳米乳化制剂(MPC-SN)在回肠段渗透系数最高,且受乳糜流动阻断剂的影响最大。结论自乳化制剂可通过肠淋巴通道增加药物吸收。脂溶性高且粒径较小的苦参碱-磷酸复合物自乳化纳米粒(MPC-SN)更易经肠淋巴系统转运。

槲皮素自微乳的抗肿瘤作用及其机制分析

目的：研究槲皮素自微乳（quercetin self-nanoemulsifying drug delivery system,Q-SNEDDS）抑制小鼠肉瘤细胞S180的分子机制。方法：制备槲皮素自微乳和空白自微乳,对其粒径和Zeta电位分别进行检测。体内实验分6组：空白组、环磷酰胺（20 mg·kg^-1）组、槲皮素自微乳高、中、低剂量（50,25,12.5 mg·kg^-1）组、槲皮素组（50 mg·kg^-1）。采用肿瘤细胞移植法建立S180移植瘤模型,用药10 d后,检测各组抑瘤率、肝指数、脾指数和胸腺指数等指标;采用实时荧光定量PCR（Realtime PCR）检测各组S180细胞的B细胞淋巴瘤-2（Bcl-2）,Bcl-2相关X蛋白（Bax）,蛋白激酶B（Akt）mRNA表达的情况;蛋白免疫印迹法（Western blot）检测各组细胞Bax,Bcl-2,Akt,磷酸化-Akt（p-Akt）的蛋白表达。结果：与空白组比较,槲皮素自微乳、环磷酰胺及槲皮素组均能抑制肿瘤细胞生长,槲皮素自微乳组抑瘤率高于槲皮素组（P〈0.05）;环磷酰胺组脏器指数低于空白组（P〈0.05）,槲皮素自微乳组脏器指数高于环磷酰胺组（P〈0.05）。与空白组比较,槲皮素自微乳上调S180细胞Bax mRNA和蛋白表达（P〈0.05）,下调S180细胞Bcl-2 mRNA和蛋白的表达（P〈0.05）,对Akt蛋白表达影响不明显,但是可以下调Akt mRNA和p-Akt蛋白的表达（P〈0.05）。结论：槲皮素自微乳具有体内抑制S180细胞的作用,槲皮素自微乳抑瘤作用高于槲皮素组。槲皮素自微乳可能通过抑制Akt信号通路,发挥其抗肿瘤的作用。