聚乳酸载药微球的制备及应用研究进展

目的介绍聚乳酸载药微球的研究情况。方法查阅数据库相关文献,较全面介绍了聚乳酸载药微球的制备方法及应用现状。结果聚乳酸载药微球具有良好的生物相容性、生物降解性、靶向性和控释性,在目前应用中还存在一些问题。结论聚乳酸载药微球在药学领域有着广阔的发展前景。     

PLA/CoFe_2O_4载药微球的制备、表征及释药性能

采用 乳化-溶剂挥发法制备了聚乳酸(polylactie acid,PLA)载硫酸庆大霉素复合微球.通过正交设计实验优选PLA载药微球的最佳实验条件.在此基础上利用微乳法制备的铁酸钴(CoFe2O4)制备了PLA/CoFe_2O_4载硫酸庆大霉素复合微球.通过透射电子显微镜(TEM)、X-射线衍射(XRD)、振动样品磁强计(VSM)对铁酸钴进行微观结构表征和性能分析.采用傅立叶变换红外光谱(FT-IR),扫描电子显微镜(SEM)、生物数码显微镜对聚乳酸载药微球和PLA/CoFe_2O_4载药微球进行了微观结构的表征和分析.结果 表明两种载药微球呈规则球形,表面光滑,分布较均匀,平均粒径约为20μm.通过体外模拟释药试验考查了PLA载药微球和PLA/CoFe_2O_4载药微球的释药性能.结果 表明聚乳酸作为药物载体具有明显的药缓控释作用,PLA/CoFe_2O_4载药微球药物释放持续的时间最长.     

辛伐他汀聚乳酸微球的制备及药剂学性质

目的:制备辛伐他汀聚乳酸微球,并考察其药剂学性质.方法:采用乳化挥发法制备辛伐他汀聚乳酸微球,用光学显微镜考察微球的粒径,用扫描电镜观察微球的形状和表面形态,用差示扫描量热法(DSC)和红外光谱法研究药物在载体中的分散状态及相互作用.结果:辛伐他汀聚乳酸微球的算术平均粒径为(42.1±2.3)μm(n=500),载药量为(22.4±0.3)%(n=3),药物包封率为(80.7±0.6)%(n=3).37℃时2种相对分子质量的聚乳酸(10 000和20 000)制备的微球体外累积释药量分别为92.68%和84.07%,释药动力学符合Higuchi方程.结论:辛伐他汀聚乳酸微球具有很好的缓控释能力.     

阿霉素聚乳酸微球的制备及体外释药特性研究

目的:对阿霉素聚乳酸微球的制备工艺、含量测定及体外释药特性进行初步研究.方法:以人工合成可生物降解聚合物聚乳酸为载体,采用乳化-溶剂挥发法制备阿霉素聚乳酸微球,用UV-260紫外分光光度计测定其药物含量和体外释药量.结果:所制备的阿霉素聚乳酸微球外形圆整,算术平均球径为55.2 μm,载药量为30.21 μg*mg-1,12 h体外累积释药量36%.结论:聚乳酸微球具有很好的控释能力,使用前景广阔.     

聚乳酸乙醇酸的生物降解和安全性研究进展

聚乳酸乙醇酸(PLGA)的降解主要是通过酯键水解,自催化作用和巨噬细胞吞噬;水解产物为乳酸和乙醇酸,均可代谢分解生成二氧化碳和水,分别通过肺和肾排出体外,仅有微量的原型聚合物经尿液排出,体内没有蓄积现象.PLGA具有良好的生物相容性和可生物降解性,作为组织工程支架和药物控释系统材料是安全的.美国食品药品管理局(FDA)已经批准将PLGA作为组织工程细胞支架和药物载体,在美国、日本市场应用多年,未见严重的不良反应报道.目前国产PLGA的质量和控释微球药品的开发研究仍需要提高,尤其是制剂的载药量、控释技术以及稳定性技术.介绍PLGA的生物降解与安全性研究进展,为开发PLGA控释系统提供参考.     

叶酸修饰的聚乳酸及其共聚物靶向给药系统研究进展

聚乳酸及其共聚物是生物性能优良的人工聚合物,是实现药物控缓释的有效载体。近年来胶束及纳米粒形式的药物载体发展迅速。此文简要介绍了对这些纳米(亚微米)尺寸药物载体叶酸表面修饰的一般方法和取得的靶向效果。修饰后,载药粒子可以较多的选择进入叶酸受体高表达的肿瘤细胞内部,而对正常细胞影响减小,可提高药物对靶标的毒性,降低药物的副作用。另外,对几个影响药物药效的因素作了简要分析,最后结合笔者的实际工作经验,提出了尚需解决的几点问题。     

聚乳酸羟基乙酸载药微球的研究进展

综述聚乳酸羟基乙酸(PLGA)载药微球的制备方法及其微球中药物释放的研究。     

局部麻醉药生物可降解缓释微球的研究进展

综述了局部麻醉药生物可降解缓释聚乳酸（PLA）微球的制备、工艺、体外释放、体内评价及相关影响因素;探讨微球制剂的载药、释药机制,为处方设计和水溶性水分子药物微球制剂的开发提供指导。     

替莫唑胺聚乳酸-羟基醋酸微球的制备及体外释药

目的:对替莫唑胺聚乳酸-羟基醋酸微球的制备工艺、含量测定及体外释药特性进行初步研究。方法:以人工合成可生物降解聚合物聚乳酸-羟基醋酸为载体,采用乳化-溶剂挥发法制备替莫唑胺聚乳酸-羟基醋酸微球,用紫外分光光度计测定其药物含量和体外释药量。结果:所制备的替莫唑胺聚乳酸-羟基醋酸微球外形圆整,算术平均球径为62.2μm,载药量为7.47%,包封率为83.53%,体外释放可达1个月。结论:替莫唑胺聚乳酸-羟基醋酸微球具有很好的控释能力,使用前景广阔。     

基于聚乳酸空间立构复合的多柔比星纳米载药胶束的制备

目的 制备了一种新型多柔比星纳米载药胶束。方法 通过开环聚合合成两亲性高分子聚合物聚乳酸-甲氧基聚乙二醇(PLA-mPEG);通过左旋的聚乳酸(PLLA)与右旋的聚乳酸(PDLA)之间的空间立构复合作用形成空间立构复合物mPEG-PLLA/mPEG-PDLA。并由两亲性分子的自组装作用形成胶束,包载阿霉素并在体外模拟载药胶束在体内的释放情况。结果 PLA-mPEG聚合物由1H NMR和红外波谱表征,通过差示扫描量热法(differential scanning calorimetry, DSC)与X射线衍射(X-ray diffraction, XRD)确证立构复合结构的形成。通过动态光散射测定空白胶束为(80±28)nm与载药胶束的粒径(160±63)nm,通过芘探针法测定胶束的临界胶束浓度(critical micelle concentration, CMC)为6.6mg/L。测得阿霉素立构复合纳米胶束的载药量为4.54%。结论 通过空间立构复合作用形成的胶束,比单一聚乳酸均聚物形成的胶束的CMC更低,载药量更高,稳定性更好。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.