Integration of phospholipid-drug complex into self-nanoemulsifying drug delivery system to facilitate oral delivery of paclitaxel

Self-nanoemulsifying drug delivery system(SNEDDS) has emerged as a promising platform to improve oral absorption of drugs with poor solubility and low permeability. However,large polarity molecules with insufficient lipid solubility,such as paclitaxel(PTX),would suffer from inferior formulation of SNEDDS due to poor compatibility. Herein,phospholipid-drug complex(PLDC) and SNEDDS were integrated into one system to facilitate oral delivery of PTX. First,PTX was formulated into PLDC in response to its inferior physicochemical properties. Then,the prepared PLDC was further formulated into SNEDDS by integrating these two drug delivery technologies into one system(PLDC-SNEDDS). After PLDC-SNEDDS dispersed in aqueous medium,nanoemulsion was formed immediately with an average particle size of ~30 nm. Furthermore,the nanomulsion of PLDC-SNEDDS showed good colloidal stability in both HCl solution(0.1 mol/l,p H 1.0) and phosphate buffer solution(PBS,p H 6.8). In vivo,PTX-PLDC-SNEDDS showed distinct advantages in terms of oral absorption efficiency,with a3.42-fold and 2.13-fold higher bioavailability than PTX-PLDC and PTX solution,respectively.Our results suggest that the integration of PLDC into SNEDDS could be utilized to facilitate the oral delivery of hydrophobic drugs with large polarity.

Self nano-emulsifying drug delivery system for Embelin:Design,characterization and in-vitro studies

CThe objective of the present study was to prepare solid self-nanoemulsifying drug delivery system(S-SNEDDS)containing Capryol-90 as oil phase for the delivery of Embelin,a poorly water soluble herbal active ingredient.Box-Behnken experimental design was employed to optimise the formulation variables,X1(amount of oil;Capryol 90),X2(amount of surfactant;Acrysol EL 135)and X3(amount of co-surfactant;PEG 400).Systems were appraised for visual characteristics for self emulsifying time,globule size and drug release.Optimised liquid formulations were formulated into free flowing granules(S-SNEDDS)by adsorption on the porous materials like Aerosil 200 and Neusilin and thereby compressed into tablet.In vitro dissolution studies of SNEDDS revealed increased in the dissolution rate of the drug.FT-IR data revealed no physicochemical interaction between drug and excipients.Solid state characterization of S-SNEDDS by DSC and Powder XRD confirmed reduction in drug crystallinity which further supports the results of dissolution studies.TEM analysis exhibited spherical globules.Further,the accelerated stability studies for 6 months revealed that S-SNEDDS of Embelin are found to be stable without any significant change in physicochemical properties.Thus,the present studies demonstrated dissolution enhancement potential of porous carrier based S-SNEDDS for poorly water soluble herbal active ingredient,Embelin.

从斯内登与杜威职业教育观之争谈高职文化素质教育

针对"职业教育"和"自由教育"是否对立的观点,回溯百年前美国斯内登和杜威间关于"职业教育"与"自由教育"的旷世论战。基于他们哲学观、教育观、职业教育观和教育对象方面的认识差异,争论结果以及对教育实践的影响认为,高职文化素质教育应走职业教育与自由教育融合的发展路径。首先,内容上体现在人类丰富的历史文化遗产"继承中的创新"精神;其次,重视师生在教育价值方面"核心价值共识"培养;最后,最终目标是实现师生共同"反省"和"精神转向"的生命状态。

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。