Bi-layered self-emulsifying pellets prepared by co-extrusion and spheronization: Influence of formulation variables and preliminary study on the in vivo absorption

The aim of this work was to produce by co-extrusion-spheronization pellets with two cohesive layers, one of them containing a self-emulsifying system for vinpocetine, a poorly water soluble model drug. Two layers were prepared: an inert layer of microcrystalline cellulose, lactose and water and a second one wetted with the self-emulsifying system. Different formulations of both layers were tested, evaluating the effects of formulation variables with an experimental design. The screening amongst formulations was performed preparing rod extrudates and using the extrusion profiles to assess their suitability for extrusion and to anticipate quality of the spheronized extrudates. Tubular extrudates and co-extrudates/spheronized pellets were then produced. Two types of bi-layered pellets were prepared: type I with the self-emulsifying system internally and the inert matrix externally, whereas type II vice versa. The pellets were characterized for sizing and shape, density, hardness, in vitro dissolution and disintegration and released droplets size and in vivo tests. Although both types of pellets demonstrated adequate morphological and technological characteristics, pellets type II revealed an improved drug solubility and in vivo bioavailability. These preliminary technological and pharmacokinetic data demonstrated that co-extrusion/spheronization is a viable technology to produce bi-layered cohesive self-emulsifying pellets of good quality and improved in vivo bioavailability.     

Amine-reactive pyridylhydrazone-based PEG reagents for pH-reversible PEI polyplex shielding

PEGylation which is reversed after the therapeutic agent reaches the target cell presents an attractive feature for drug, protein or nucleic acid delivery. Amine-reactive, endosomal pH cleavable polyethylene glycol aldehyde-carboxypyridylhydrazone, N-hydroxysuccinimide esters (PEG-HZN-NHS) were synthesized and applied for bioreversible surface shielding of DNA polyplexes. Monofunctional mPEG-HZN-NHS was synthesized by reacting succinimidyl hydraziniumnicotinate with mPEG-butyraldehyde (20 kDa). Bifunctional OPSS-PEG-HZN-NHS was synthesized analogously via a omega-2-pyridyldithio-PEG (10 kDa) propionaldehyde intermediate. Polyethylenimine (PEI) polyplexes were reacted with the pH-sensitive (mPEG-HZN-NHS) or the corresponding stable (mPEG-NHS) reagent. Both types of polyplexes remained shielded at pH 7.4 as demonstrated by particle size and zeta potential measurements after 4h of incubation at 37 degrees C. Polyplex deshielding at endosomal pH 5 was observed only with the mPEG-HZN-NHS shielded particles. This was confirmed by fluorescence correlation spectroscopy using the analogous Alexa-488 fluorescently labeled bifunctional PEGylation reagents. Luciferase gene transfections with epidermal growth factor (EGF) containing polyplexes using EGF-receptor overexpressing hepatoma HUH7 cells showed an up to 16-fold enhancement in gene expression with the reversibly shielded polyplexes as compared to stably shielded polyplexes. Consistently, the reversibly shielded polyplexes mediated also an enhanced tumor specific in vivo transgene expression after intravenous administration in a subcutaneous HUH7 tumor model in SCID mice.     

冰片对血眼屏障通透性的影响

目的:研究冰片对家兔血眼屏障通透性的影响。方法:将42只家兔随机分为实验组和对照组,每组21只。实验组给予冰片(0.8g/kg)灌胃,对照组等体积溶媒灌胃,给药后15min耳缘静脉注射20g/L伊文思蓝(EB),分别经5,15,30,45,60,90,120min取房水及玻璃体。采用荧光分光光度法检测房水及玻璃体中的EB浓度。结果:与对照组相比,实验组房水和玻璃体中EB含量更高。结论:冰片可提高家兔血眼屏障的通透性,是一种有效促进药物透过血眼屏障的穿透促进剂。这将为某些内眼疾病的药物治疗提供新方法。     

透皮促渗方法联合应用的研究进展

透皮给药系统具有传统给药方式不可比拟的优势。但由于药物的低渗透量，使其应用受到一定限制。各种物理的、化学的促渗方法，包括透皮吸收促进剂、超声导入法、离子导入法、电穿孔法等可改善皮肤透过性，增加药物的透皮速率。而且几种方法联合应用的促渗效果更加显著。本文总结了近年来各种促渗方法联合应用的研究进展。     

有关巨大儿相关围产因素变化的探讨

目的:探讨近年来巨大儿相关围产因素的变化。方法:回顾性分析我院分娩巨大儿的完整在案病历共435例,按年份分为1984年组、1994年组及2004年组。比较及分析3组巨大儿的发生率、产科相关因素、剖宫产率及剖宫产指征的变化情况。结果:3年间巨大儿的发生率分别为4.57%、6.06%及9.91%(P<0.05)。巨大儿孕妇的剖宫产率分别为56.55%、61.33%及84.38%(P<0.01)。3组巨大儿孕妇择期及临产后剖宫产率:1984年组与1994年组比较均无显著性差异(P>0.05)。1984年组及1994年组各与2004年组比较均有显著性差异(P<0.05)。3组剖宫产手术指征的变化:无论是临产后或择期手术以家属要求为指征的剖宫产率均呈上升趋势(P<0.001)。3组比较巨大儿合并过期妊娠的发生率分别为11.9%、9.3%及2.1%(P<0.001)。而巨大儿合并经产妇的发生率则分别为8.9%、13.3%及18.8%(P<0.01)。结论:对存在可能发生巨大胎儿倾向因素的孕妇适当采取一些有效的措施,尽量减少巨大胎儿的发生是降低剖宫产率及保障母婴安全的一项重要措施。     

孕期体重指数及其增长对分娩方式的影响

目的探讨孕妇孕期体重指数及其增长对分娩方式的影响。方法分析480例单胎足月妊娠妇女孕前体重指数(BMI)以及整个孕期体重指数增长(△BMI)对分娩方式的影响。结果超体重组剖宫产率明显高于低体重组及理想体重组,差异有高度统计学意义(P<0.01)。当△BMI>6.0时,剖宫产率及阴道助产率明显高于其它两组,差异有统计学意义(P<0.05)。结论孕期体重指数及其孕期体重指数的变化是影响分娩方式的重要因素。     

壳聚糖结肠靶向释药体系的初步研究

目的:制备壳聚糖作载体的结肠靶向给药制剂,并评价其体外释药性能。方法:将亚甲蓝与壳聚糖形成小丸,再以丙烯酸树脂(Ⅱ)包裹该小丸,以分光光度法测定其体外释放性能。结果:该小丸在pH1.2盐酸溶液及pH6.8磷酸缓冲液中药物累积释放量8h内小于6%,而在人工结肠液中,14h时累积释放度为38%左右。结论:用丙烯酸树脂(Ⅱ)包膜的壳聚糖制剂具有潜在的结肠靶向释药效果。     

气囊助产术临床应用分析

目的探讨气囊助产仪在临床分娩中的作用。方法随机选择初产妇1226例，观察组613例（应用气囊助产），对照组613例。观察两组产妇的产程、分娩方式及围产情况。结果观察组的第一、二产程与总产程明显缩短；阴道分娩率大大提高、剖宫产率降低、新生儿1min Apgar评分、产后2h出血量及母乳喂养情况与对照组相比有统计学差异（P〈0．05）；宫颈撕伤率、产后感染率两组无显著性差异（P〉0．05）。结论气囊助产术可缩短产程，减少产妇疼痛，降低软产道损伤，增加阴道分娩率，降低剖宫产率，减少产后出血和产后尿潴留。     

Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo

The goal of this study was to enhance gene delivery and tumor cell transfection in vivo by using a combination of ultrasonication with complex nanoparticles consisting of two types of nanoparticles: PEI/DNA β-gal plasmid with highly positive zeta-potential and air-filled poly (lactic-co-glycolic acid) (PLGA) particles (with negative zeta-potential) manufactured in our laboratory. The PLGA/PEI/DNA nanoparticles were a colloid with positive zeta-potential and injected i.v. in nude mice with DU145 human prostate tumors. We found that the combination of PLGA/PEI/DNA nanoparticles with ultrasonication substantially enhanced tumor cell transfection in vivo. The overexpression of β-gal gene was evaluated histochemically and by Western blot analysis. At least an 8-fold increase of the cell transfection efficacy was obtained in irradiated tumors compared to non-irradiated controls, while little to no cell death was produced by ultrasonication.     

伊曲康唑自乳化释药系统的处方研究

 目的研究伊曲康唑自乳化给药系统(ITZ-SEDDS)的处方工艺。方法通过溶解度实验?处方配伍和伪三相图的绘制,以自乳化时间?色泽和粒径的大小为指标,筛选油相、表面活性剂、助表面活性剂的最佳搭配和处方配比。并对ITZ-SEDDS的理化性质和体外溶出度进行了测定。结果伊曲康唑自乳化最终优化处方为:Maisine 35-1-Cremophor EL-Transcutol P=25∶30∶45。ITZ-SEDDS的粒径为162.5 nm,自乳化时间<1 min,ITZ-SEDDS在人工肠液中2 h累积溶出百分率为90.9%,是原药(0.52%)的174.8倍,市售胶囊(10.1%)的9.0倍。结论所制备的ITZ-SEDDS达到了设计要求,为ITZ的新制剂开发提供了实验依据。