Circulating microparticles in cardiovascular disease: implications for atherogenesis and atherothrombosis

Summary. The complex and multifactorial nature of atherogenesis and development of atherothrombotic complications involves numerous interactions between various cell types inside the vascular wall (e.g. macrophages and smooth muscle cells) and in the blood (e.g. leukocytes and platelets). One relatively recent advance in this area is the discovery of circulating microparticles and their role in endothelial damage, platelet activation, hypercoagulability and regulation of inter‐cellular interactions. Microparticles are small anucleoid phospholipid vesicles released from different cells, such as platelets, erythrocytes, leukocytes and endothelial cells. Microparticles carry surface proteins and include cytoplasmic material of the parental cells responsible for the exertion of microparticle‐mediated biological effects. About 25% of the procoagulant activity of stimulated platelet suspensions is associated with microparticles released upon platelet activation and their surface may be approximately 50–100‐fold more procoagulant than the surface of activated platelets per se. The available lines of evidence indicate that shedding of microparticles from the parental cells is not just a passive process accompanying cellular dysfunction and apoptosis, but a tightly regulated mechanism implicated in the interactions between various cell types. The role of microparticles as biological messengers is supported by their differential and specific involvement in the pathophysiology of different cardiovascular disorders, including atherogogenesis and thrombosis.     

Freeze drying of orally disintegrating tablets containing taste masked naproxen sodium granules in blisters

Abstract

Orally disintegrating tablets (ODTs) were freeze dried in blisters using the Lyostar® II SMART? Freeze Dryer Technology. ODT formulations either without non-water soluble particles (placebo) or containing large fractions (717?mg) of taste-masked naproxen sodium (NaS) granules were freeze dried. The process data revealed differences between ODTs with and without embedded granules in the pressure rise curves as well as in the shelf (inlet) temperature adjustments during freeze-drying. Pressure rise curves of the placebo ODTs from eight hours process time showed no distinct temperature-dominated part, and the last optimization step of the shelf temperature to achieve ?24.4?°C might be prone to errors. The final shelf temperature of ODTs containing granules was ?23.3?°C. The detection of primary drying endpoints using SMART? Technology or comparative pressure measurements was reliable for both ODT formulations, whereas the application of thermocouples resulted in premature endpoint indication. Product resistance of ODTs containing granules was generally elevated in comparison to ODTs without granules, but increased only slightly over the course of the drying process. In summary, the developed freeze-drying cycle was found applicable for production of elegant ODTs with incorporated taste masked NaS granules.     

Carboxymethyl xanthan microparticles as a carrier for protein delivery

Xanthan gum (XG) was derivatized to sodium carboxymethyl xanthan gum (SCMXG) and then cross-linked with aluminium ions (Al⁺³) to prepare BSA-loaded microparticles (MPs) from a completely aqueous environment. The derivatized gum was characterized by various physical methods. Discrete and spherical BSA-loaded MPs were obtained from SCMXG solution, the pH of which was adjusted to 6 and 7 and the BSA entrapment efficiency was found to reach as high as 82%. The protein release in acidic dissolution medium was faster than that in alkaline dissolution medium and was accounted for the higher swelling ratio of the MPs in acidic environment. Moreover, the pH of the gum solution used to prepare the MPs also influenced the swelling and consequently protein release considerably.     

Polyurethane-based microparticles: Formulation and influence of processes variables on its characteristics

This study reports the development of polyurethane-based microparticles and the influence of some processes variables on its characteristics. These microparticles were prepared by emulsion polymerization, using poly(caprolactone) diol (PCL) and poly(propylene glycol), tolylene 2,4-diisocyanate terminated (TDI) or poly(propylene oxide)-based tri-isocyanated pre-polymer (TI). The reaction of polymerization was confirmed by attenuated total internal reflection Fourier transformed infrared spectroscopy (ATR-FTIR). Their thermal characteristics were investigated by dynamical mechanical thermal analysis (DMTA) and thermogravimetric analysis (TGA). For good microparticles formation, formulation 80/20 (mass ratio isocyanate/PCL) was the most indicated. Their spherical shape and smooth surface were observed by optical and scanning electron microscopy (SEM). Zeta potential measurements suggest that ionized carbonyl groups existent at the surface can be responsible for the negative potentials obtained. Respecting size and size distribution of the particles, measured by laser diffraction spectroscopy (LDS), the stirring speed and type were the process variables that most influenced it.     

Drug development in Parkinson's disease: From emerging molecules to innovative drug delivery systems

Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood–brain barrier and target a specific region are still needed.     

淋巴细胞微粒的形成及其活性

淋巴细胞的主要生理功能是参与机体特异性的免疫应答及调节,可进一步分为T淋巴细胞、B淋巴细胞,分别执行细胞免疫功能和体液免疫功能.活化的淋巴细胞能够表达和释放多种细胞因子和蛋白等,同时,当淋巴细胞受刺激活化或凋亡时从浆膜上脱落成直径为0.05-1.00 μm的小囊泡颗粒,形成淋巴细胞微粒(lymphocyte-derived microparticles, LMPs).     

内皮衍生微粒诱导内皮细胞氧自由基产生损伤内皮功能

目的： 探讨内皮衍生微粒（EMP)诱导内皮功能失调的机制和氧自由基(O-·2)在EMP诱导内皮功能失调中所起的作用。方法: 从人血纤维蛋白溶酶原激活抑制剂-1刺激的人脐静脉内皮细胞中提取EMP,(1)采用牛主动脉内皮细胞（BAEC）做细胞培养,分成3组。第1组不做预处理,第2组EMP (1×108/L),第3组EMP(1×108/L) + L-nitroarginiemethylester(L-NAME, 1 mmol/L),预处理BAEC 30 min后,用超氧化物歧化酶(SOD)可抑制的铁细胞色素C还原法,测量O-·2的产生情况。(2) 从小鼠中分离面动脉,分成4组。第1组不做预处理,第2组EMP (1×108/L),第3组EMP(1×108/L) + SOD (2×105 U/L),第4组EMP (1×108/L)+聚乙烯羟乙酸盐超氧化物歧化酶(PEG-SOD, 2×105 U/L) 预处理血管10 min后做乙酰胆碱（ACH）诱导下的内皮依赖血管舒张功能试验。结果:（1）EMP明显增加BAEC O-·2产生,L-NAME可以抑制50% EMP导致的 O-·2产生增加。 (2) EMP明显损伤ACH诱导的血管舒张功能,SOD处理未能清除EMP对血管舒张功能的损伤,PEG-SOD可部分恢复EMP处理后的血管舒张功能。结论: EMP诱导血管内皮功能失调至少部分是通过诱导细胞内产生的O-·2所致,为将来寻找包括清除O-·2在内的综合治疗方法提供理论依据。