Polyester-based microparticles of different hydrophobicity: the patterns of lipophilic drug entrapment and release

The paper is devoted to the investigation of the effect of polyester hydrophobicity and ability for crystallisation on lipophilic drug loading and release from microparticles fabricated on the base of these polymers. Poly(l-lactic acid), poly(d, l-lactic acid) and poly (lactic acid-co-glycolic acid) were synthesised by ring-opening polymerisation using stannous octoate as catalyst, while poly(caprolactone) (PCL) and poly(ω-pentadecalactone) (PPDL) formation was catalysed by lipase. The particles were formed via single emulsion evaporation/diffusion method. The particles obtained were studied using SEM, XRD and DSC methods. The degradation of particles based on different polyesters, entrapment and release of a model hydrophobic drug (risperidone®) were thoroughly studied. The effect of particles hydrophobicity and crystallinity on these parameters was of most interest. The drug entrapment is greater for the hydrophobic polymers. Drug release was more rapid from crystalline particles (PLLA, PCL, PPDL), than from amorphous PDLLA and PLGA ones.     

复方木尼孜其颗粒联合四环素治疗寻常型痤疮的临床疗效观察

目的观察复方木尼孜其颗粒联合四环素治疗寻常型痤疮的临床疗效。方法 85例患者随机分为治疗组43例和对照组42例,对照组仅给予四环素治疗,治疗组在对照组治疗基础上加用复方木尼孜其颗粒。2组疗程均为6周。观察比较2组治疗后第2、4、6周临床疗效和不良反应。结果治疗组治疗后第2、4、6周总有效率分别为88.37%、90.70%、95.35%,高于对照组的69.05%、71.43%、78.57%,差异均有统计学意义(P<0.05)。2组均未见严重不良反应。结论复方木尼孜其颗粒联合四环素治疗寻常型痤疮疗效满意,无明显不良反应,值得临床推广使用。     

肾康注射液的配伍稳定性考察

摘 要 目的：考察肾康注射液与10%葡萄糖注射液的配伍稳定性。方法: 将肾康注射液与10%葡萄糖注射液的配伍液置于室温、光照（4 500Lx）和40℃恒温条件,考察不同条件下0,1,2,4,8,12,24,48 h配伍液的性状、pH、不溶性微粒,以及大黄酸和大黄素的含量。结果: 配伍液在放置过程中性状、pH无明显变化。室温条件下,配伍液在4 h后微粒数有所增加;光照和40℃恒温条件下,2 h时配伍液的微粒数明显增加。大黄酸和大黄素的含量随放置时间的延长而下降,其中大黄酸在光照条件下降最明显,大黄素在光照和40℃恒温条件下降低将近10%。结论:肾康注射液与10%葡萄糖注射液配伍后最好在4 h内输注完,滴注过程应在室温条件（10～30℃）下进行,并避免强光照射。     

68Ga‐Ca‐phytate particles: A potential lung perfusion agent of synthetic origin prepared in a cold kit format

The objective of this study was to investigate the radiosynthesis of ⁶⁸Ga‐Ca‐phytate particles and then characterize the formulation for radiochemical purity, radioactive particle size distribution, and biodistribution in normal rats. This radiotracer was prepared using a commercial phytate cold kit after reconstitution with saline, ⁶⁸Ga‐chloride generator eluent, calcium chloride, and air, then heating at 100°C for 30 minutes to achieve 99% radiochemical purity of ⁶⁸Ga‐particles that were 21% 3–5 μm, 8% 5–15 μm, and 71% >15 μm in diameter. This optimal formulation was stable for 2 hours at room temperature. Intravenous administration of ⁶⁸Ga‐particles in rats resulted in an uptake of 93% in the lungs, 4% in the liver plus spleen, and 3% in the carcass after 20 minutes. Two‐thirds of the carcass activity was radioactive blood, likely to be ⁶⁸Ga‐transferrin. The positron emission tomography image was superior than the ^99mTc‐MAA image because it displayed high lung uptake against a low background. Low uptake by the liver, spleen did not interfere with the diagnostic quality, and faint activity in the submandibular (salivary) glands was due to ⁶⁸Ga‐transferrin. The preclinical data so far indicate that ⁶⁸Ga‐Ca‐phytate particles have good potential as a lung perfusion imaging agent.     

钩薄过敏颗粒对咳嗽变异性哮喘大鼠Th1/Th2类细胞因子水平的影响

目的：探讨钩薄过敏颗粒对咳嗽变异性哮喘（cough variant asthma,CVA）大鼠Th1/Th2类细胞因子水平的影响及其可能的作用机制。方法：利用卵蛋白和氢氧化铝共同激发致敏建立CVA大鼠模型;分为正常对照组、模型组、钩薄过敏颗粒组和地塞米松组,记录诱咳时2 min内大鼠咳嗽次数及血清中白介素-4（IL-4）、干扰素（IFN-γ）和嗜酸粒细胞阳离子蛋白（ECP）的含量。结果：与正常对照组比较,模型组咳嗽次数明显增多（P＜0.01）,血清中IL-4、ECP含量显著升高（P＜0.01）,IFN-γ含量显著降低（P＜0.01）,钩薄过敏颗粒组经治疗后咳嗽次数明显减少（P＜0.01）,血清中IL-4、ECP含量明显降低、IFN-γ含量明显升高（P＜0.01）。结论：钩薄过敏颗粒对咳嗽变异性哮喘大鼠有治疗作用,其机制可能与调控Th1/Th2平衡有关。     

Nitrogen dioxide: no influence on allergic sensitization in an intranasal mouse model with ovalbumin and diesel exhaust particles

The role of traffic-related air pollution in the development of allergic diseases is still unclear. We therefore investigated if NO₂, an important constituent of traffic-related air pollution, promotes allergic sensitization to the allergen ovalbumin (OVA). We also examined if NO₂ influenced the allergy adjuvant activity of diesel exhaust particles (DEP). For this purpose, mice were exposed intranasally to OVA with or without DEP present, immediately followed by exposure to NO₂ (5 or 25 parts per million [ppm]) or room air for 4?h in whole body exposure chambers. Eighteen hours after the last of three exposures, the lungs of half of the animals were lavaged with saline and markers of lung damage and lung inflammation in the bronchoalveolar lavage fluid (BALF) were measured. Three weeks later, after intranasal booster immunizations with OVA, the levels of OVA-specific IgE and IgG2a antibodies in serum were determined. Both NO₂ (25?ppm) and DEP gave lung damage, measured as increased total protein concentration in BALF, whereas only NO₂ seemed to stimulate release of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In contrast, only DEP significantly increased the number of neutrophils. Furthermore, DEP in combination with OVA stimulated the production of serum allergen-specific IgE antibodies. NO₂, however, neither increased the production of allergen-specific IgE antibodies, nor influenced the IgE adjuvant activity of DEP. Thus, based on our findings, NO₂ seems to be of less importance than combustion particles in the development of allergic diseases after exposure to traffic-related air pollution.     

Siderite (FeCO3) and magnetite (Fe3O4) overload-dependent pulmonary toxicity is determined by the poorly soluble particle not the iron content

The two poorly soluble iron containing solid aerosols of siderite (FeCO₃) and magnetite (Fe₃O₄) were compared in a 4-week inhalation study on rats at similar particle mass concentrations of approximately 30 or 100?mg/m³. The particle size distributions were essentially identical (MMAD ≈1.4 μm). The iron-based concentrations were 12 or 38 and 22 or 66?mg Fe/m³ for FeCO₃ and Fe₃O₄, respectively. Modeled and empirically determined iron lung burdens were compared with endpoints suggestive of pulmonary inflammation by determinations in bronchoalveolar lavage (BAL) and oxidative stress in lung tissue during a postexposure period of 3 months. The objective of study was to identify the most germane exposure metrics, that are the concentration of elemental iron (mg Fe/m³), total particle mass (mg PM/m³) or particle volume (μl PM/m³) and their associations with the effects observed. From this analysis it was apparent that the intensity of pulmonary inflammation was clearly dependent on the concentration of particle-mass or -volume and not of iron. Despite its lower iron content, the exposure to FeCO₃ caused a more pronounced and sustained inflammation as compared to Fe₃O₄. Similarly, borderline evidence of increased oxidative stress and inflammation occurred especially following exposure to FeCO₃ at moderate lung overload levels. The in situ analysis of 8-oxoguanine in epithelial cells of alveolar and bronchiolar regions supports the conclusion that both FeCO₃ and Fe₃O₄ particles are effectively endocytosed by macrophages as opposed to epithelial cells. Evidence of intracellular or nuclear sources of redox-active iron did not exist. In summary, this mechanistic study supports previous conclusions, namely that the repeated inhalation exposure of rats to highly respirable pigment-type iron oxides cause nonspecific pulmonary inflammation which shows a clear dependence on the particle volume-dependent lung overload rather than any increased dissolution and/or bioavailability of redox-active iron.     

Pre- and postnatal exposure to low-dose diesel exhaust impairs murine spermatogenesis

We investigated whether pre- and postnatal low-dose exposure to diesel exhaust (DE) affects male reproductive function in mice. The DE concentration is less than that indicated as the environmental quality standard for suspended particulate matter (SPM) in Japan. ICR mice were exposed prenatally to low-dose diesel exhaust (0.17?mg of DE particles/m³) through the airway for 8?h/day in an exposure chamber from gestational day 2 until the examination. In the DE-exposed groups, normal sperm morphology in the epididymis was reduced (p?<?0.01), and seminiferous tubules showed degenerative changes in which the number of Sertoli cells was decreased (p?<?0.01). Those changes were observed at 6 and 12 weeks of age. Furthermore, ultrastructural studies revealed an increase in damaged mitochondria in Sertoli cells (p?<?0.001) and variform spermatozoa. These results indicate that pre- and postnatal exposure of low-dose DE is detrimental to Sertoli cell function and may cause abnormal spermatozoa.     

Changing the dose metric for inhalation toxicity studies: Short-term study in rats with engineered aerosolized amorphous silica nanoparticles

Inhalation toxicity and exposure assessment studies for nonfibrous particulates have traditionally been conducted using particle mass measurements as the preferred dose metric (i.e., mg or μg/m³). However, currently there is a debate regarding the appropriate dose metric for nanoparticle exposure assessment studies in the workplace. The objectives of this study were to characterize aerosol exposures and toxicity in rats of freshly generated amorphous silica (AS) nanoparticles using particle number dose metrics (3.7?×?10⁷ or 1.8?×?10⁸ particles/cm³) for 1- or 3-day exposures. In addition, the role of particle size (d₅₀?=?37 or 83?nm) on pulmonary toxicity and genotoxicity endpoints was assessed at several postexposure time points. A nanoparticle reactor capable of producing, de novo synthesized, aerosolized amorphous silica nanoparticles for inhalation toxicity studies was developed for this study. SiO₂ aerosol nanoparticle synthesis occurred via thermal decomposition of tetraethylorthosilicate (TEOS). The reactor was designed to produce aerosolized nanoparticles at two different particle size ranges, namely d₅₀?=?～30?nm and d₅₀?=?～80?nm; at particle concentrations ranging from 10⁷ to 10⁸ particles/cm³. AS particle aerosol concentrations were consistently generated by the reactor. One- or 3-day aerosol exposures produced no significant pulmonary inflammatory, genotoxic, or adverse lung histopathological effects in rats exposed to very high particle numbers corresponding to a range of mass concentrations (1.8 or 86?mg/m³). Although the present study was a short-term effort, the methodology described herein can be utilized for longer-term inhalation toxicity studies in rats such as 28-day or 90-day studies. The expansion of the concept to subchronic studies is practical, due, in part, to the consistency of the nanoparticle generation method.