Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation

In this article, a hydrophobic (beclomethasone dipropionate; BDP) and a hydrophilic (cytarabine; Ara-C) drugs have been encapsulated in liposomes in order to be administered via the pulmonary route. For this aim, a liposome preparation method, which is easy to scale up, the ethanol injection method, has been selected. The effects of critical process and formulation parameters have been investigated. The drug-loaded liposomes were prepared and characterized in terms of size, zeta potential, encapsulation efficiency, release study, cell uptake, and aerodynamic behavior. Small multilamellar vesicles, with sizes ranging from about 80 to 170?nm, were successfully obtained. Results indicated a significant influence of phospholipid and cholesterol amounts on liposome size and encapsulation efficiency. The higher encapsulation efficiencies were about 100% for the hydrophobic drug (BDP) and about 16% for the hydrophilic one (Ara-C). The in vitro release study showed a prolonged release profile for BDP, in contrast with Ara-C, which was released more rapidly. The cell-uptake test revealed that fluorescent liposomes have been well internalized into the cytoplasm of SW-1573 human lung carcinoma cells, confirming the possibility to use liposomes for lung cell targeting. Nebulized Ara-C and BDP liposomes presented aerodynamic diameters compatible with deep lung deposition. In conclusion, the elaborated liposomes seem to be promising carriers for both Ara-C and BDP pulmonary delivery.     

Alternate glucocorticoid receptor ligand binding structures influence outcomes in an in vivo tissue regeneration model

Since their characterization, glucocorticoids (GCs), the most commonly prescribed immunomodulatory drugs, have undergone numerous structural modifications designed to enhance their activity. In vivo assessment of these corticosteroid analogs is essential to understand the difference in molecular signaling of the ligands that share the corticosteroid backbone. Our research identified a novel function of GCs as modulators of tissue regeneration and demonstrated that GCs activate the glucocorticoid receptor (GR) to inhibit early stages of tissue regeneration in zebrafish (Danio rerio). We utilized this phenomenon to assess the effect of different GC analogs on tissue regeneration and identified that some GCs such as beclomethasone dipropionate (BDP) possess inhibitory properties, while others, such as dexamethasone and hydrocortisone have no effect on regeneration. We performed in silico molecular docking and dynamic studies and demonstrated that type and size of substitution at the C17 position of the cortisol backbone confer a unique stable conformation to GR on ligand binding that is critical for inhibitory activity. In the field of tissue regeneration, our study is one of the first Structure Activity Relationship (SAR) investigations performed in vertebrates demonstrating that the in vivo tissue regeneration model is a powerful tool to probe structure function relationships, to understand regenerative biology, and to assist in rational drug design.     

小型猪血浆中二丙酸倍他米松及其代谢物倍他米松的LC-MS/MS 同时测定方法的建立及在药动学研究中的应用

目的：建立同时测定小型猪血浆中二丙酸倍他米松及其代谢物倍他米松的LC-MS/MS 法,并研究小型猪皮肤外用二丙酸倍他米松乳膏后,二丙酸倍他米松及倍他米松的药动学特征。方法：血浆样品经酸化后以乙醚- 环己烷（4 ∶ 1）提取,LC-MS/MS 分析,以Hedera ODS-2（150 mm×2.1 mm,5 μm）为分析柱,流动相为5 mmol?L-1 醋酸铵水溶液（含0.1% 乙酸）– 甲醇,梯度洗脱。二丙酸倍他米松、倍他米松及内标布地奈德的监测离子对分别为m /z 563.2（[M+CH3COO]-）→ 483.1、m /z 451.2（[M+CH3COO]-）→ 361.0 和m /z 489.3（[M+CH3COO]-）→ 357.1。对小型猪外用二丙酸倍他米松乳膏后其血浆中二丙酸倍他米松及代谢物倍他米松的浓度进行测定,并计算主要药动学参数。结果：二丙酸倍他米松血药浓度在26.85~644.4 ng?L-1 范围内线性关系良好,倍他米松血药浓度在10.62~637.2 ng?L-1 范围内线性关系良好。结论：本方法专属性强、简便、灵敏,可用于血浆样本中二丙酸倍他米松及其代谢物倍他米松的测定及药动学研究。     

Study of the RESS Process for Producing Beclomethasone-17,21-Dipropionate Particles Suitable for Pulmonary Delivery

The purpose of this research was to micronize beclomethasone-17,21-dipropionate (BDP), an anti-inflammatory inhaled corticosteroid commonly used to treat asthma, using the rapid expansion of supercritical solution (RESS) technique. The RESS technique was chosen for its ability to produce both micron particles of high purity for inhalation, and submicron/nano particles as a powder handling aid for use in next generation dry powder inhalers (DPIs). Particle formation experiments were carried out with a capillary RESS system to determine the effect of experimental conditions on the particle size distribution (PSD). The results indicated that the RESS process conditions strongly influenced the particle size and morphology; with the BDP mean particle size decreasing to sub-micron and nanometer dimensions. An increase in the following parameters, i.e. nozzle diameter, BDP mol fraction, system pressure, and system temperature; led to larger particle sizes. Aerodynamic diameters were estimated from the SEM data using three separate relations, which showed that the RESS technique is promising to produce particles suitable for pulmonary delivery.     

The thyroid C cells of ovariectomized rats treated with estradiol

The structure and function of thyroid C cells were studied in ovariectomized (Ovx) adult female rats without and after chronic treatment with estradiol dipropionate (EDP). A peroxidase–antiperoxidase method was applied for localization of calcitonin (CT) in the C cells. Morphometric changes in their volume, nuclei, and relative volume density were evaluated in comparison with sham-operated control rats using a stereological method. The number of C cells was calculated. CT content in the sera was determined by radioimmunoassay. Ovariectomy (Ovx) led to a 21% increase in body weight (P<0.005), while treatment of Ovx rats with EDP decreased body weight by 25% (P<0.01). The immunoreactivity for CT in C cells of the Ovx rats was markedly increased. Significant decreases in the volume of C cells (by 13%; P<0.05) and serum CT (by 45%) were recorded, while the C cell number increased by 59% (P<0.05) in relation to the corresponding controls. The treatment of Ovx rats with EDP caused conspicuous degranulation of the C cells. The cellular volume was increased by 11% and serum CT by 36% in comparison with Ovx animals. At the same time a decrease in C cell number by 29% (P<0.05) was evident. It may be concluded that estradiol deficiency after Ovx reduced the synthesis and release of CT, while chronic treatment of these animals with EDP had a positive effect on the secretory activity of thyroid C cells.     

The Effect of Estradiol Dipropionate on the Rate of Protein Synthesis in the Testicle of the Sea Urchin Strongylocentrotus nudus

The effect of estradiol dipropionate on the rate of protein synthesis in the testicle of the mature sea urchin Strongylocentrotus nuduswas studied. The injection of this estrogen considerably intensified ³H-leucine incorporation into the gonad. The change in the level of cell synthetic activity is assumed to be associated with a rise in effective incorporation of ³H-leucine into proteins following an increase in its intracellular level, and with an increase in the protein synthesis rate. The participation of sex hormones in the regulation of protein synthesis in the S. nudusgonad is discussed.     

基于高分辨质谱及分子对接技术研究适配体与倍氯米松的相互作用

倍氯米松(beclomethasone)是一种有效的糖皮质激素,而倍氯米松适配体是对倍氯米松具有亲和力与特异性的单链DNA分子.目前对两者的相互作用仍不清楚,研究适配体与药物的相互作用对适配体的应用具有一定的意义.本研究采用高分辨傅里叶变换离子回旋共振质谱仪(FT-MS)及分子对接软件计算模拟研究适配体与倍氯米松的相互...