Toxicology Test and Safety Evaluation of Cefquinome Sulfate Liposomes

The purpose of this study was to evaluate the safety of the cefquinome sulfate liposomes by using the acute toxicity test, local irritation test and chronic toxicity test. The results showed that the LD₅₀ of cefquinome sulfate liposomes was 639.73 mg/kg after intramuscular injection of its suspension and 95% confidence interval was 573.06 to 714.17 mg/kg. There was no significant stimulation to muscle. Subchronic toxicity test showed that the weight, haematological indexes and biochemical criterion of rabbits in variety dose had no significant difference compared with normal group (P>0.05). There was no visible pathological changes on the liver,kidney histology. According to pathological observation, the structure of liver and kidney were clear in treated and middle dose groups,but there existed disorganized hepatic cell cord in the liver and hemorrhag between glomerulopathy,tubulointerstitial and hepatic sinusoids in high dose group. All results proved that the cefquinome sulfate liposomes was safe and reliable based on the animal experiments.     

Nano- and Microdelivery Systems for Marine Bioactive Lipids

There is an increasing body of evidence of the positive impact of several marine lipids on human health. These compounds, which include ω-3 polyunsaturated fatty acids, have been shown to improve blood lipid profiles and exert anti-inflammatory and cardioprotective effects. The high instability of these compounds to oxidative deterioration and their hydrophobicity have a drastic impact in their pharmacokinetics. Thus, the bioavailability of these compounds may be affected, resulting in their inability to reach the target sites at effective concentrations. In this regard; micro/nanoparticles can offer a wide range of solutions that can prevent the degradation of targeted molecules, increase their absorption, uptake and bioavailability. In this work we will present the options currently available concerning micro- and nanodelivery systems for marine lipids; with emphasis on micro/nanoparticles; such as micro/nanocapsules and emulsions. A wide range of bottom-up approaches using casein, chitosan, cyclodextrins, among others; will be discussed.     

玉屏风多糖脂质体的制备及表征研究

优选玉屏风多糖脂质体的最佳工艺并对其进行表征验证。采用逆向蒸发法制备玉屏风多糖脂质体,以膜材比、脂药比和超声时间为考察因素,包封率为评价指标,采用L9(34)正交试验设计优选制备条件,以超速离心法测定包封率,体外释药试验验证,纳米颗粒分析仪和透射电镜测定其粒径大小与形态。制备玉屏风多糖脂质体的最佳工艺为膜材比8∶1,脂药比4∶1,超声时间90s,包封率88.38%,24h累积释放率73.45%,平均粒径132.65nm。制备的玉屏风多糖脂质体具有较高的包封率与良好的缓释作用,粒径和形态较均匀,重现性好。     

Reduced metribuzin pollution with phosphatidylcholine-clay formulations

BACKGROUND: Metribuzin is a widely used herbicide that has been identified as a groundwater contaminant. In this study, slow‐release formulations of metribuzin were designed by encapsulating the active ingredient in phosphatidylcholine (PC) vesicles and adsorbing the vesicles onto montmorillonite. RESULTS: The maximum active ingredient content in the slow‐release formulations was 246 g kg^?1. Infrared spectroscopy results revealed that the hydrophobic interactions between metribuzin and the alkyl chains on PC were necessary for encapsulation. In addition, water bridges connecting the herbicide and the PC headgroup enhanced the solubility of metribuzin in PC. Adsorption experiments in soils were performed to evaluate the relationship between sorption and leaching. Funnel experiments in a sandy soil revealed that the herbicide was not irreversibly retained in the formulation matrix. In soil column experiments, PC–clay formulations enhanced herbicide accumulation and biological activity in the top soil layer relative to a commercial formulation. PC–clay formulations also reduced the dissipation of metribuzin by a factor of 1.6–2.5. CONCLUSIONS: A reduction in the recommended dose of metribuzin can be achieved by employing PC–clay formulations, which reduces the environmental risk associated with herbicide applications. Moreover, PC and montmorillonite are non‐toxic and do not negatively affect the environment. Copyright © 2010 Society of Chemical Industry     

pH-Dependent Solution Structure and Activity of a Reduced Form of the Host-Defense Peptide Myticin C (Myt C) from the Mussel Mytilus galloprovincialis

Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to the immune response in the mediterranean mussel (Mytilus galloprovincialis), which has shown to be active across species due to its strong antiviral activity against a fish rhabdovirus found in fish cells overexpressing this HDP. However, the potential antimicrobial properties of any synthetic analogue of Myt C has not yet been analysed. Thus, in this work we have synthesised the sequence of the mature peptide of Myt C variant c and analysed the structure activity relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to results previously reported for oxidized isoforms of mussel myticins, red-MytCc was not active against bacteria at physiological pH and showed a moderate antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus. However, its chemotactic properties remained active. Structure/function studies in neutral and acid environments by means of infrared spectroscopy indicated that the structure of red-MytCc is pH dependent, with acid media increasing its alpha-helical content. Furthermore, red-MytCc was able to efficiently aggregate artificial phospholipid membranes at low pH, as well as to inhibit the Escherichia coli growth, suggesting that this activity is attributable to its more structured form in an acidic environment. All together, these results highlight the dynamic and environmentally sensitive behavior of red-Myt C in solution, and provide important insights into Myt C structure/activity relationships and the requirements to exert its antimicrobial/immunomodulatory activities. On the other hand, the pH-dependent direct antimicrobial activity of Myt C suggests that this HDP may be a suitable template for the development of antimicrobial agents that would function selectively in specific pH environments, which are sorely needed in this “antibiotic-resistance era”.     

CONCOMITANT LIPOSOMAL DOXORUBICIN AND DAILY PALLIATIVE RADIOTHERAPY IN ADVANCED FELINE SOFT TISSUE SARCOMAS

Local recurrence of feline soft tissue sarcomas is common despite aggressive treatment. Liposomal doxorubicin might serve as a depot radiosensitizer if administered concomitantly with daily radiotherapy and thus improve tumor control. In this pilot study, the feasibility of concomitant liposomal radiochemotherapy was evaluated in a palliative setting in 10 cats with advanced soft tissue sarcomas. Cats were treated with median number of 5 (range 5–7) daily fractions of radiotherapy and a median total dose of 20 Gy (range 20–31.5 Gy). One dose of liposomal doxorubicin was administered at the beginning of radiotherapy. Seven cats received further free or liposomal doxorubicin after completion of the liposomal doxorubicin/radiation protocol. Seven of the treated 10 cats (70%) achieved a partial (n=5) or complete (n=2) response with a median response duration of 237 days. The median progression free interval in all 10 cats was 117 days and the median overall survival time was 324 days. Concomitant liposomal radiochemotherapy was tolerated well in nine cats, one cat experienced temporary anorexia. Although the number of patients is too small to make definitive conclusions, results appear promising enough to investigate the role of liposomal doxorubicin as a radiosensitizer further.     

吡喹酮脂质体对实验动物的毒性作用研究

为探明吡喹酮脂质体对实验动物是否具有毒性作用,分别进行了急性和亚急性毒性试验,肝功能及血常规检查,结果表明,吡喹酮脂质体对小白鼠的半数致死量（ＬＤ５０）为腹腔注射１８６５ｍｇ／ｋｇ,分别以１／２０和１／１０ＬＤ５０的剂量隔天给小白鼠腹腔注射,连续试验７０ｄ,均无临床病理变化,给供试兔耳静脉注射该制剂１０ｍｇ／ｋｇ,给药后１－５ｄ的肝功能和血液生理生化指标同给药前相比均无显著差异。     

大黄酚磁性脂质体制备工艺研究

目的研究大黄酚磁性脂质体的制备工艺。方法采用薄膜超声法制备大黄酚磁性脂质体,以包封率为评价指标,通过单因素考察和正交试验优化处方。结果大黄酚磁性脂质体的最佳处方为:药脂比为1∶15,膜材比为5.5∶1,成膜温度50℃,水化介质为pH值为6.6的PBS溶液。最优处方下平均包封率为(64.93±1.49)%。结论优选处方和制备工艺稳定可行,采用薄膜超声法制备的大黄酚磁性脂质体包封率较高。     

高效液相色谱法测定伊维菌素脂质体药物的含量及包封率

本试验旨在建立伊维菌素脂质体载体药物含量及包封率测定的高效液相色谱法。Waters surfire C18柱(150 mm×2.1 mm,5 μm),流动相为乙腈—甲醇—水(62∶30∶8),流速1 mL/min,检测波长245 nm,进样量10 μL,柱温30 ℃。采用凝胶过滤法、透析法、冷冻超速离心法、超滤离心法4种方法对脂质体与药物进行分离。结果表明,在优化色谱条件下伊维菌素与辅料及溶剂峰均得到良好分离,伊维菌素在1～50 μg/mL浓度范围内线性关系良好(r=0.9998,n=5),最终采用超速冷冻离心法可将脂质体与药物很好的分离,伊维菌素脂质载体的包封率可达98.54%±1.6%。该方法准确可靠、简单快速,可用于伊维菌素脂质体载体药物含量及包封率的测定。     

左旋咪唑脂质体的制备及特性

应用注入法制备了位径为250±21nm的左旋咪唑大单层脂质体,并获得20％以下的药物包裹率.包裹率受药脂比和脂质组成的影响.制备脂质体的有机相、脂质成分是影响左旋咪唑脂质体稳定性的重要因素.综合结果表明,以氯仿为有机相,药脂比定为1:100(W/W),脂质成分比为卵磷脂:胆固醇=5:1时,用100℃煮沸灭菌药物渗漏小于10％,且贮存稳定,是制备左旋咪唑脂质体的适宜条件.灭菌后,脂质体的形态经电镜观察无明显变化.