Vesicular aceclofenac systems: a comparative study between liposomes and niosomes

Vesicular delivery systems have been reported to serve as local depot for sustained drug release. Aceclofenac multilamellar liposomes and niosomes were prepared and a comparative study was done between them through evaluation of entrapment efficiency, particle size, shape, differential scanning calorimetry and in vitro drug release. A stability study was carried out by investigating the leakage of aceclofenac and the change in the vesicles particle size when stored at (2-8 degrees C) for 3 months. The anti-inflammatory effect of aceclofenac vesicles was assessed by the rat paw oedema technique. Results showed that the entrapment efficiency and the in vitro release of aceclofenac from the vesicles can be manipulated by varying the cholesterol content, the type of surfactant as well as the type of charge. Niosomes showed better stability than liposomes. Both vesicular systems showed significant sustained anti-inflammatory activity compared to the marketed product, with niosomes being superior to liposomes as manifested by both oedema rate and inhibition rate percentages suggesting their effectiveness as topical anti-inflammatory delivery systems.     

Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilising phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localised effects and relatively few studies showing transdermal delivery effects. Shortly after this, transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial, with diverse processes being reported. Parallel to this development, other classes of vesicles were produced, with ethanol being included into the vesicles to provide flexibility (as in ethosomes); vesicles were constructed from surfactants and cholesterol (as in niosomes). The ultradeformable vesicles showed variable efficiency in delivering low-molecular-weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs, considering both their efficacy and their potential mechanisms of action.     

脂质体物理稳定性和包封率的影响因素

脂质体制备的难点在于改善物理稳定性和提高包封率.现从脂质体的常用制备方法、投料和投料比、制备过程中的条件控制及贮存条件等方面考察其对脂质体的物理稳定性和包封率的影响.     

Non-invasive vaccine delivery in transfersomes, niosomes and liposomes: a comparative study

Non-invasive vaccine delivery is a top priority for public health agencies because conventional immunization practices are unsafe and associated with numerous limitations. Recently, the skin has emerged as a potential alternative route for non-invasive delivery of vaccine. Topical immunization (TI), introduction of antigen through topical application onto the intact skin, has many practical merits compared to injectable routes of administration. One of the possibilities for increasing the penetration of bioactives through the skin is the use of vesicular systems. Specially designed lipid vesicles are attracting intense attention and can be used for non-invasive antigen delivery. In the present study, elastic vesicle transfersomes, non-ionic surfactant vesicles (niosomes) and liposomes were used to study their relative potential in non-invasive delivery of tetanus toxoid (TT). Transfersomes, niosomes and liposomes were prepared and characterized for shape, size and entrapment efficiency. These vesicles were extruded through polycarbonate filter (50-nm pore size) to assess the elasticity of the vesicles. The immune stimulating activity of transfersomes, niosomes and liposomes were studied by measuring the serum anti-TT IgG titre following topical immunization. The immune response elicited by topical immunization was compared with that elicited by same dose of alum-adsorbed tetanus toxoid (AATT) given intramuscularly. The results indicate that optimal formulations of transfersomes, niosomes and liposomes could entrap 72.7+/-3.4, 42.5+/-2.4 and 41.3+/-2.2% of antigen and their elasticity values were 124.4+/-4.2, 29.3+/-2.4 and 21.7+/-1.9, respectively. In vivo study revealed that topically given TT containing transfersomes, after secondary immunization, could elicit immune response (anti-TT-IgG) that was equivalent to one that produced following intramuscularly alum-adsorbed TT-based immunization. In comparison to transfersomes, niosomes and liposomes elicited weaker immune response. Thus transfersomes hold promise for effective non-invasive topical delivery of antigen(s).     

Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole: A comparative assessment

The objective of work was to formulate, evaluate and compare the transdermal potential of novel vesicular nanocarriers: ethosomes and ultradeformable liposomes, containing clotrimazole (CLT), an anti-fungal bioactive. The ethosomal formulation (ET₄) and ultradeformable liposomal (UL) formulation (TT₃) showed highest entrapment 68.73 ± 1.4% and 55.51 ± 1.7%, optimal nanometric size range 132 ± 9.5 nm and 121 ± 9.7 nm, and smallest polydispersity index 0.027 ± 0.011 and 0.067 ± 0.009, respectively. The formulation ET₄ provided enhanced transdermal flux 56.25 ± 5.49 μg/cm²/h and decreased the lag time of 0.9 h in comparison to TT₃ formulation (50.16 ± 3.84 μg/cm²/h; 1.0 h). Skin interaction and FT-IR studies revealed greater penetration enhancing effect of ET₄ than TT₃ formulation. ET₄ formulation also had the highest zone of inhibition (34.6 ± 0.57 mm), in contrast to TT₃ formulation (29.6 ± 0.57 mm) and marketed cream formulation (19.0 ± 1.00 mm) against candidal species. Results suggested ethosomes to be the most proficient carrier system for dermal and transdermal delivery of clotrimazole.     

DC-Chol/DOPE cationic liposomes: A comparative study of the influence factors on plasmid pDNA and siRNA gene delivery

Cationic liposomes (CLs) composed of 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidylethanolamine (DOPE) (DC-Chol/DOPE liposomes) have been classified as one of the most efficient gene delivery systems. Our study aims to examine the effect of the molar ratio of DC-Chol/DOPE, PEGylation and serum on the pDNA (plasmid pDNA) and siRNA (small interfering RNA) transfection of DC-Chol/DOPE liposomes. The results showed that the most efficient DC-Chol/DOPE liposomes for pDNA or siRNA delivery were at a 1:2 or 1:1 molar ratio of DC-Chol/DOPE, respectively. The transfection efficiency of DC-Chol/DOPE liposomes increased along with increased weight ratio of DC-Chol/siRNA. However, the pDNA transfection efficiency decreased along with increased weight ratio of DC-Chol/pDNA from 3/1. As expected, PEGylation decreased siRNA and pDNA transfection efficiency of DC-Chol/DOPE liposomes. In PEGylated DC-Chol/DOPE liposomes, increased weight ratio of DC-Chol/pDNA from 3/1 did not lead to higher pDNA transfection efficiency, whereas increased weight ratio of DC-Chol/siRNA resulted in increased siRNA transfection efficiency. Furthermore, the serum did not significantly inhibit the pDNA and siRNA transfection efficiency of DC-Chol/DOPE liposomes. In conclusion, our results elucidated the influence factors of DC-Chol/DOPE liposome transfection and would reveal that siRNA and pDNA transfection mechanisms were different in DC-Chol/DOPE liposomes.     

Comparison of gastrointestinal safety and tolerability of aceclofenac with diclofenac: a multicenter,randomized, double-blind study in patients with knee osteoarthritis

Abstract

Objective:

To compare the gastrointestinal (GI) tolerability and efficacy of aceclofenac with diclofenac in patients with knee osteoarthritis (OA).     

A comparative study of stabilising effect and antioxidant activity of different antioxidants on levodopa-loaded liposomes

The aim of this study was to evaluate the stability of levodopa liposomes co-loaded with three different antioxidants (curcumin, ascorbic acid, and superoxide dismutase (SOD)). For this purpose, multilamellar liposomes were prepared. Curcumin was added into the lipid bilayer while ascorbic acid and SOD were placed into the aqueous phase. The influence of preparation technique and surface charge were also investigated. Vesicles were characterised and free radical scavenging potential was determined. From stability study, ascorbic acid showed better stabilising effect. These co-loaded liposomes also exhibited potential radical scavenging activity where ascorbic acid played a key role. From the study of different preparation techniques and charge, we concluded that cationic liposomes made by Thin Layer Evaporation following extrusion offered the best physicochemical and stability properties. A dual mechanism of these liposomes implies the chemical stabilisation of levodopa (dose reduction) and the antioxidant effect, with a preventive effect on Parkinson’s disease.     

Enhanced oral bioavailability of etodolac by self‐emulsifying systems: in‐vitro and in‐vivo evaluation

Objectives The objective of this study was to prepare a self‐emulsifying drug delivery system (SEDDS) for oral bioavailability enhancement of a poorly water‐soluble drug, etodolac. The SEDDS formulations were optimized by evaluating their ability to self‐emulsify when introduced to an aqueous medium under gentle agitation, and by determination of the particle size of the resulting emulsion. Methods An optimized formulation of SEDDS (composed of 20% etodolac, 30% oil Labrafac WL1349, 10% Lauroglycol 90 and 40% Labrasol) was selected for bioavailability assessment in rabbits. The anti‐inflammatory effect was also determined in rats, and compared with powder drug and etodolac suspension in water (50 mg/kg). Key findings The peak plasma concentration of 16.4 ± 1.1 μg/ml appeared after 1.3 ± 0.2 h, whereas with powder drug and etodolac suspension the values were 7.5 ± 0.5 and 10.6 ± 0.7 μg/ml at 4.2 ± 0.4 and 2.4 ± 0.2 h, respectively. The AUC_0–8 of the etodolac SEDDS formulation was 2.3 times that of the pure drug and 1.4 times that of the suspension form. SEDDS formulation exhibits a 21% increase in paw thickness compared with a 39% increase on oral administration of etodolac suspension after 4 h at the same dose of the drug (20 mg/kg). Conclusions The result indicates the utility of SEDDS for the oral delivery of etodolac and potentially other lipophilic drugs.     

三七总皂苷脂质体的生理适应性及其对心脑血管的保护作用

目的：研究三七总皂苷(PNs)脂质体的生理适应性及其对心脑血管的保护作用。方法：采用蟾蜍上腭纤毛运动持续时间、大鼠肺水肿指数以及肺组织病理改变作为指标，考察PNS脂质体的生理适应性；通过结扎大鼠冠状动脉建立急性心肌梗死模型以及夹闭蒙古沙土鼠双侧颈总动脉建立脑缺血一再灌注模型，观察PNS脂质体对心脑血管疾病的作用。结果：PNS脂质体组蟾蜍黏膜纤毛运动持续时间是对照组的92．14％，大鼠的肺水肿指数和肺组织病理改变与PNS溶液组相比有显著差异，接近对照组。PNS脂质体在降低大鼠心肌梗死范围和缓解沙土鼠脑缺血一再灌注过程中出现的卒中指数时呈剂量依赖性，大剂量效果更优。结论：PNS脂质体具有良好的生理适应性，对实验性心肌梗死和脑缺血一再灌注均有较好的保护作用。     

Thymoquinone in liposomes: a study of loading efficiency and biological activity towards breast cancer

Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone) is a herbal-derived drug with potential chemopreventive and chemotherapeutic activity. However, thymoquinone suffers from high hydrophobicity causing poor solubility which limits its bioavailability and high lipophilicity causing poor formulation characteristics. Liposomes are versatile drug carriers that can be used to solve problems of drug solubility, instability, and bio-distribution. In this study, we were able to prepare thymoquinone-loaded liposomes (TQ-LP) and thymoquinone loaded in liposomes modified with Triton X-100 (XLP) with diameters of about 100?nm, and entrapment efficiency of more than 90% for TQ-LP and of 49.6% for XLP. The TQ-LP liposomes were effective in suppressing the proliferation of breast cancer cell lines MCF-7 and T47D, and at the same time exerting very low toxicity on normal periodontal ligament fibroblast. Altogether, this report describes the first successful encapsulation of thymoquinone into liposome; which maintains stability, improves bioavailability and maintains its anticancer activity.     

荧光素作为酸敏指示剂评价酸敏材料和脂质体酸敏性的方法研究

目的:建立一种简单而快速的评价酸敏材料和脂质体酸敏性的实验分析方法。方法:利用脂质体包裹的荧光素在高浓度环境的自屏蔽作用,以及从脂质体中释放后自屏蔽消失的特性,通过检测试样的荧光发射光信号,来评价酸敏物质诱发细胞膜融合通透性能的强弱和脂质体的酸敏释药性能。结果:选用不同磷脂组分制备的脂质体可以成功的包裹高浓度荧光素,被包裹的荧光素稳定并且能屏蔽自己的发射光;在酸性条件,酸敏物质破坏脂质体膜,荧光素可以从脂质体中释放出来。酸敏材料的酸敏能力、溶液酸度、脂质体磷脂组成都影响荧光素从脂质体中释放的能力和速度;酸度影响荧光素的荧光强度,但在 pH 6.5～10.0不受影响。结论:利用脂质体包裹高浓度荧光素的自我屏蔽性,建立一种简单而快速的实验方法,用来评价酸敏物质诱发细胞膜融合通透性能的强弱以及评价脂质体的酸敏释药性能。     

Irritative action of alcoholic beverages in rat stomachs: A comparative study with ethanol

The mucosal irritative action of alcoholic beverages such as white wine, Japanese sake and whisky was examined in rat stomachs in vivo and in vitro, in comparison with ethanol. The concentration of ethanol in these alcoholic beverages was 15%. Mucosal application of ethanol (15%) and whisky in the chambered stomach caused a decrease in gastric potential difference (PD), while that of Japanese sake and white wine caused a slight increase but not decrease in PD. Likewise, both ethanol and whisky markedly reduced the cell viability of RGM1 cells after 5 min incubation, whereas neither Japanese sake nor white wine had any effect. In addition, supplementation of glucose, one of the non-alcoholic ingredients of white wine and Japanese sake, antagonized a reduction in both PD and cell viability caused by ethanol. These results suggest that the mucosal irritative action of Japanese sake and white wine is much less than that of ethanol or whisky and that these properties may be, at least partly, due to the glucose contained in these alcoholic beverages.     

Zeta电位及其在药学分散体系研究中的应用

依据国内外文献，介绍、总结Zeta电位的测定方法及其在药学分散体系研究中的应用。Zeta电位的测定方法有微量电泳法、电泳光散射法和电-声效应法，其在乳剂、混悬剂及脂质体等的研究中具有十分重要的作用。Zeta电位为研究药物分散体系物理稳定性的一个重要参数。     

喹诺酮类新药KNT和盐酸莫西沙星肝毒性的比较研究

目的 采用大鼠原代肝细胞模型评价盐酸莫西沙星(Mox)和喹诺酮类新药KNT的体外肝毒性.方法 胶原酶二步灌流法分离制备SD大鼠肝细胞,进行原代培养.Mox和KNT分别设1.6、0.8、0.4、0.2、0.1 mg·mL-1剂量组,同时设溶剂对照组,处理24 h后,检测对比肝细胞活力IC50、AST、胞内LDH泄漏情况、GSH含量变化及两药物不同浓度处理后受损的肝细胞线粒体在电子显微镜下状态的对比.结果 KNT的细胞生长抑制率IC50=0.773 mg· mL-1,显著低于Mox(IC50=1.144 mg·mL-1).Mox在0.8 mg·mL-1剂量处理24 h后,对大鼠原代肝细胞生长抑制率约69％,培养液上清AST和LDH水平显著升高,肝细胞GSH含量显著降低,电镜观察到肝细胞内绝大部分线粒体肿胀,嵴断裂消失;而Mox在0.4 mg·mL-1剂量下,细胞生长抑制率约8％,AST、LDH和GSH含量无明显改变.经0.8 mg· mL-1 KNT处理24 h后,对细胞生长抑制率约9％,培养液上清AST、LDH水平显著低于0.8 mg· mL-1 Mox的,与空白对照比有上升趋势,GSH水平也显著上升,电镜观察到肝细胞核轻微固缩,部分线粒体肿胀.在0.4 mg· mL-1 KNT剂量下,细胞生长抑制率约1％,AST、LDH和GSH含量无明显改变.结论 同剂量下,KNT处理大鼠原代肝细胞24 h后,表现出比Mox肝细胞毒性弱.     

安徽省城乡小学生身体形态与机能研究

目的了解安徽省城乡小学生身体形态与机能情况。方法以安徽省参加2010年全国学生体质健康调研的7～12岁汉族小学生共4 488人为研究对象,分析安徽省城乡小学生身体形态与机能的差异。结果安徽省小学生身体形态、机能城乡间均存在差异。城市同龄男、女生身高均高于乡村,男生8～、10～、12岁、女生7～、8～9、～1、1～岁组间差异有统计学意义(P<0.05)。城市同龄男、女生体重均高于乡村男、女生,男生各年龄组,女生7～、8～、9～、11～岁组间差异有统计学意义(P<0.05)。城市同龄男、女生胸围均高于乡村男、女生,男生各年龄组,女生7～、9～、11～岁组间差异有统计学意义(P<0.05)。城市同龄男、女生BMI指数均高于乡村男、女生,男生8～、10～、11～、12岁,女生7～、12岁组差异有统计学意义(P<0.05)。肺活量城市男生各年龄组,女生除7～8、～岁组外均高于乡村,女生11～岁组差异有统计学意义(P<0.05)。肺活量体重指数城市男、女生除10～1、1～岁组外均低于乡村,男生各年龄组,女生7～8、～、11～岁组差异有统计学意义(P<0.05)。结论安徽省城市小学生的身体形态与机能普遍优于乡村小学生。     

β内酰胺酶抑制剂——他佐巴坦与舒巴坦抑酶作用比较研究

目的比较β内酰胺酶抑制剂——他佐巴坦与舒巴坦抑酶作用强弱。方法用紫外分光光度法及微生物法研究比较了他佐巴坦与舒巴坦对３０株临床分离酶、８株标准酶的抑酶保护作用。结果他佐巴坦对９株大肠杆菌产生的β内酰胺酶的抑制作用强于舒巴坦，而对其他临床分离酶的抑酶作用与舒巴坦相同。他佐巴坦对ＯＸＡ－１，ＯＸＡ－２，ＯＸＡ－３，ＴＥＭ－１，ＴＥＭ－２，Ｐ９９，Ｋ－ＣＡＺ的抑制作用明显强于舒巴坦。但对Ｋ１酶、他佐巴坦与舒巴坦均无明显抑制作用。结论他佐巴坦对β内酰胺酶的抑制作用强于舒巴坦。     

DNA-based therapeutics and DNA delivery systems: A comprehensive review

The past several years have witnessed the evolution of gene medicine from an experimental technology into a viable strategy for developing therapeutics for a wide range of human disorders. Numerous prototype DNA-based biopharmaceuticals can now control disease progression by induction and/or inhibition of genes. These potent therapeutics include plasmids containing transgenes, oligonucleotides, aptamers, ribozymes, DNAzymes, and small interfering RNAs. Although only 2 DNA-based pharmaceuticals (an antisense oligonucleotide formulation, Vitravene, (USA, 1998), and an adenoviral gene therapy treatment, Gendicine (China, 2003), have received approval from regulatory agencies; numerous candidates are in advanced stages of human clinical trials. Selection of drugs on the basis of DNA sequence and structure has a reduced potential for toxicity, should result in fewer side effects, and therefore should eventually yield safer drugs than those currently available. These predictions are based on the high selectivity and specificity of such molecules for recognition of their molecular targets. However, poor cellular uptake and rapid in vivo degradation of DNA-based therapeutics necessitate the use of delivery systems to facilitate cellular internalization and preserve their activity. This review discusses the basis of structural design, mode of action, and applications of DNA-based therapeutics. The mechanisms of cellular uptake and intracellular trafficking of DNA-based therapeutics are examined, and the constraints these transport processes impose on the choice of delivery systems are summarized. Finally, the development of some of the most promising currently available DNA delivery platforms is discussed, and the merits and drawbacks of each approach are evaluated.     

Lysine-containing cationic liposomes activate the NLRP3 inflammasome: Effect of a spacer between the head group and the hydrophobic moieties of the lipids

Cationic lipids containing lysine head groups and ditetradecyl, dihexadecyl or dioctadecyl glutamate hydrophobic moieties with/without propyl, pentyl or heptyl spacers were applied for the preparation of cationic liposomes using a simple bath type-sonicator. The size distribution, zeta potential, cellular internalization, and cytotoxicity of the liposomes were characterized, and the innate immune stimulation, e.g., the NLRP3 inflammasome activation of human macrophages and THP-1 cells, was evaluated by the detection of IL-1β release. Comparatively, L3C14 and L5C14 liposomes, made from the lipids bearing lysine head groups, ditetradecyl hydrophobic chains and propyl or pentyl spacers, respectively, were the most potent to activate the NLRP3 inflammasome. The possible mechanism includes endocytosis of the cationic liposomes and subsequent lysosome rupture without significant inducement of reactive oxygen species production. In summary, we first disclosed the structural effect of cationic liposomes on the NLRP3 inflammasome activation, which gives an insight into the application of nanoparticles for improved immune response.     

双源CT冠状动脉成像与冠状动脉造影的对比研究

目的探讨双源CT冠状动脉成像(DSCTCA)对冠状动脉斑块的诊断价值。方法选取50例疑诊冠心病患者,使用双源CT进行冠状动脉成像,并于3周内行冠状动脉造影(CAG)。与CAG的结果进行对比,了解DSCTCA对于冠状动脉斑块的种类、大小、慢性完全闭塞病变(CTO)以及解剖学分布的诊断价值。结果 50例患者中,DSCTCA显示的冠状动脉直径≥1.5 mm节段有580个,571个节段可进行评估,共检测出129个粥样硬化斑块,检出率为23%,其中69%为大斑块,28%为小斑块,70%为钙化斑块,CTO病变共检出4个,心肌桥(MB)5个,与CAG相比,DSCTCA诊断冠状动脉斑块的敏感性、特异性、阳性预测值、阴性预测值分别为98.3%、97.3%、92.2%、99.1%。结论 DSCTCA能评价冠状动脉狭窄程度,对钙化病变、CTO病变、MB的诊断具有较高的准确性和敏感性,可作为高危人群冠心病筛查的首选方法。