Recent progress of respiratory inhalation drug delivery systems

With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.

Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention

Objective： Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery ofanticancer drugs to the lungs. Methods： q-he following nanocarriers were studied： micelles, liposomes, mesoporous silica nanoparticles （MSNs）, poly propyleneimine （PPI） dendrimer-siRNA complexes nanoparticles, quantum dots （QDs）, and poly （ethylene glycol） polymers. All particles were characterized using the following methods： dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto- and genotoxicity. In vivo organ distribution of all nanopartides, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice after the pulmonary or intravenous delivery. Results： Significant differences in lung uptake were found after the inhalation delivery of lipid-based and non-lipid-based nanoparticles. The accumulation ofliposomes and miceUes in lungs remained relatively high even 24 h after inhalation when compared with MSNs, Q Ds, and PPI dendrimers. There were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h after inhalation or intravenous administrations, but 24 h after intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes significantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer. Conclusion： The results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers after the inhalation delivery. These particles are most suitable for effective inhalation treatment of lung cancer.

The role of caveolin-1 in the biofate and efficacy of anti-tumor drugs and their nano-drug delivery systems

As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored.In addition,the interplay between caveolin-1 and nano-drugs is bidirectional.Caveolin-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of cells.This article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

Gather wisdom to overcome barriers:Well-designed nano-drug delivery systems for treating gliomas

Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy.Although these strategies can be used clinically to overcome the blood-brain barrier(BBB),the accurate delivery of drugs to the glioma lesions cannot be ensured.Nano-drug delivery systems(NDDS)have been widely used for precise drug delivery.In recent years,researchers have gathered their wisdom to overcome barriers,so many well-designed NDDS have performed prominently in preclinical studies.These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions,drug release in response to the glioma microenvironment,biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein,and carriers created according to the active ingredients of traditional Chinese medicines.We reviewed these well-designed NDDS in detail.Furthermore,we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy,and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

Inhalable microparticles as drug delivery systems to the lungs in a dry powder formulations

Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases.Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution,leading to a more effective therapy with reduced required doses and side effects.On the other hand,there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical,aerodynamic and biological properties,which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result.Therefore,we focused on powders consisting of polysaccharides,lipids,proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers.We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms.This review article addresses the most common manufacturing methods with novel modifications,pros and cons of different materials,drug loading capacities with release profiles,and biological properties such as cytocompatibility,bactericidal or anticancer properties.

Studies on the in Vitro Dissolution of Insoluble Volatile Drug from Su-Anxin Nasal Inhalant and Its Correlation on the Nose Steady Self-Controllable Expiration and Inspiration at Night

In the paper, the in vitro dissolution of borneol in 12 hours from 6 batches of optimized inhalant samples were investigated. As a new dosage form, the in vitro release apparatus of nasal inhalant was invented and a pushing bump was used according to the simulation of the nose expiration and inspiration. Based on the data of r2 in the profile and similar factor f2 from 6 linear release tendencies, a good controlled release and a zero order tendency were observed. It can be suggested that there is a good correlation between the in vitro controlled release and the nose steady self-controllable expiration and inspiration, which will contribute to the trend of insoluble volatile drug controlled release and the effect of quick absorption in nasal pulmonary delivery to cure severe or acute cardiovascular or lung diseases at patients' sleeping, such as angina or breathing obstruction. Also, it was concluded that the prescription composed of insoluble volatile drugs can be prepared to be nasal inhalant from which drugs can be absorbed through nose steady self-controllable inspiration to the lung then into the blood and have a great effectiveness improvement of bioavailability at night timing drug delivery system.

治疗肺部疾病的中药活性成分可吸入纳米给药系统研究进展

肺部给药能直接将药物运送至肺部,是肺部疾病的优选给药方式。中药活性成分如槲皮素、紫杉醇等对肺部疾病具有良好的治疗效果,但其存在水溶性差和肺清除率高等问题。将中药活性成分负载在纳米给药系统中,可提高药物的水溶性、稳定性及其在肺部的渗透性和滞留性。基于此,本研究综述了治疗肺部疾病的中药活性成分可吸入纳米给药系统的研究进展,发现有基于壳聚糖、脂质(包括脂质体、固体脂质纳米粒、纳米结构脂质载体)、靶向配体(包括靶向叶酸受体、靶向转铁蛋白受体、外泌体)的中药活性成分可吸入纳米给药系统,这些纳米给药系统综合考虑了粒径、表面电荷和疏水性等关键因素,可避免药物被黏液、纤毛和巨噬细胞清除,具有较好的应用潜力。

Smart drug delivery systems for precise cancer therapy

Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.

一种简单的吸入一氧化氮的输送系统

目的 解决国内在缺乏昂贵ＮＯ浓度监测仪的情况下应用一氧化氮吸入疗法技术的难题。方法 １７只犬随机分为二组，吸入性损伤模型成功后，对照组单纯吸氧（ＦｉＯ２，０．４５），治疗组吸氧（ＦｉＯ２，０．４５）＋０．００４５％（４５ｐｐｍ）ＮＯ。ＮＯ输送系统由三个转子流量计分别控制 Ｏ２，Ｎ２和 ＮＯ三种气体管道出口，按需调节三股气体流量比例，在呼吸回路的吸入支置钠石灰罐。 ＦｉＯ２和二氧化氮（（ＮＯ２）数据行多个样本均间方差分析，ＮＯ行两样本均数间ｔ检验。结果ＦｉＯ２实测值比预计值高１０．８％（Ｐ＞０．０５），ＮＯ２在钻石灰处理后比钠石灰处理前降低８０．２％（Ｐ＜０．０１），ＮＯ实测值比预计值高１１％（Ｐ＞０．０５）。结论 本系统既避免了产生过高ＮＯ２的危险，同时又克服了ＮＯ浓度不恒定的缺点，能较好地满足基础实验研究。

吸入给药的新进展

目的:综述吸入给药系统最新研究进展和实践成果。方法:根据国内外发表的文献和重要会议论文,对吸入给药的研究和应用进行综合与分析。结果:阐明了吸入给药的优越性,并对吸入给药剂型装置的种类、优缺点、选择和使用方法以及吸入治疗的发展方向加以综述。结论:吸入给药系统具有广阔的应用前景。

靶控输注异丙酚及静脉输注瑞芬太尼用于小儿麻醉与静吸复合麻醉的比较

目的比较靶控输注(TCI)异丙酚、静脉输注瑞芬太尼用于小儿麻醉与静吸复合麻醉对血流动力学的影响及苏醒期特点。方法选择40例行扁桃体或增殖体切除术的患儿,年龄4～12岁,ASAⅠ～Ⅱ级,随机分为全静脉麻醉(TIVA)组和静吸复合麻醉(C)组,每组20例。常规麻醉诱导后,TIVA组采用靶控输注异丙酚、静脉输注瑞芬太尼维持麻醉,C组采用吸入异氟醚及静脉输注异丙酚维持麻醉。手术结束后立即停止所有药物的输入。记录术中的血压(BP)、心率(HR)、脉搏氧饱和度(SpO2)和术毕停药后自主呼吸恢复时间、呼之睁眼时间、拔管时间;观察患儿拔管后即刻、1h、3h的意识状态(OAAS评分)以及术后躁动和恶心呕吐的发生率。结果C组术中的HR较TIVA组明显增快,并且苏醒期躁动的发生率也较TIVA组高。2组术后自主呼吸恢复时间、睁眼时间、拔管时间差异无显著性,但TIVA组拔管后即刻、1h的OAAS评分高于C组。结论靶控输入异丙酚、静脉输注瑞芬太尼用于小儿是一种较好的麻醉方法,与静吸复合麻醉比较术中的HR较低、苏醒质量较优良。

胰岛素超细化处理及其吸入给药系统的基础研究

综述胰岛素超细化处理方法及其吸入给药系统基础研究的最新进展 。

丙泊酚复合瑞芬太尼靶控静脉麻醉与静吸复合麻醉的临床观察

目的:比较丙泊酚复合瑞芬太尼靶控静脉麻醉与静吸复合麻醉的诱导和术后苏醒过程.方法:选腹腔镜胆囊切除术40例,ASA I—II级,15—66岁,随机分为静吸复合麻醉(C)组,丙泊酚瑞芬太尼靶控(R)组,每组20例,观察麻醉诱导,气管插管时的血压、心率,术毕停药后病人自主呼吸恢复时间,呼之睁眼时间,拔管时间,离开手术室时间,观察恶心、呕吐情况.结果:C组诱导时的收缩压低于R组,低血压者多于R组,插管反应发生率R组低于C组;二组病人术后自主呼吸恢复时间,呼之睁眼时间,拔管时间差异无显著性,恶心、呕吐发生率差异无显著性.结论:与静吸复合麻醉相比,异丙酚瑞芬太尼靶控输注麻醉诱导更平稳.

肺部药物递送系统在肺部感染治疗领域的现状和进展

近年来,社区获得性肺炎成为最为常见的肺部感染,发病群体极为广泛,造成严重的健康威胁。本文对抗菌药物细菌耐药性、药物递送系统(DDS)在肺部感染治疗方面的优势和研究难点等研究进行归纳和总结,简要介绍了抗菌药物在肺部治疗的现状,针对肺部感染的药物递送,特别是针对铜绿假单胞菌(PA)感染,讨论了目前肺部递送抗菌药物载体的研究进展及药物递送系统与肺部生物屏障的相互作用,以期为解决抗菌药物治疗方面面临的重大问题和克服肺部生物学屏障、提高药物在感染病灶的生物利用度提供一种新的思路。

一种干粉定量给药装置的结构设计与性能分析

我们设计了一种体积较小、便于随身携带,操作简单及生产成本低的新型干粉定量给药装置——干粉定量吸入装置。本研究分析了干粉吸入装置的结构与工作原理,并对装置的零部件进行了设计计算与分析。通过释药稳定性实验研究,同时模拟人的吸入药物过程。测出每次实验吸出的药物质量,实验结果数据在期望值上下10%范围内波动,验证了结构的合理性,对新型干粉定量吸入装置的临床应用奠定了基础。

不同靶浓度普鲁泊福对上腹部手术病人七氟烷呼气末有效浓度的影响

目的观察不同靶浓度普鲁泊福(短效静脉麻醉药)对上腹部手术患者七氟烷(吸入麻醉药)呼气末有效浓度的影响。方法60例择期上腹部手术的病人随机分为3组:S组,麻醉诱导后,单纯吸入七氟烷维持麻醉;P1组和P2组在吸入七氟烷的同时,分别输注靶浓度为1、2μg·mL-1的普鲁泊福。麻醉诱导气管插管后,启动靶控输注普鲁泊福,并根据脑电双频谱指数(BIS)值的变化调节七氟烷吸入浓度,维持BIS值在45～55。结果呼气末七氟烷有效浓度S组为(1.74±0.14)%,P1组为(1.24±0.08)%,P2组为(0.82±0.09)%,P1组较S组降低28.7%;P2组较S组降低52.9%,P1组的血压更稳定。结论复合1、2μg·mL-1靶浓度的普鲁泊福,七氟烷的呼气末浓度分别下降28.7%和52.9%;以靶浓度为1μg·mL-1的普鲁泊福与七氟烷复合麻醉,对稳定血流动力学更有效。

不同药物释放系统的体外评价方法研究进展

作为在一定程度上可预测药物体内行为的体外实验,是制剂评价和质量控制的重要研究内容。本文照不同的释药系统分类,综述了口服、透皮、吸入、直肠或阴道给药系统的体外评价方法及其研究进展。

吸入给药系统的应用及进展

本文对吸入给药系统的临床应用及最新研究进展进行了综述。通过查阅近年来国内外发表的相关文献,阐述了吸入给药独特的优势,介绍了吸入给药装置的种类、选择和使用方法。吸入给药系统具有广阔的应用前景。

呼吸道吸入药物递送系统的研究进展

随着人口老龄化、吸烟人群年轻化以及空气污染严重化等诸多因素的影响,慢性呼吸道疾病发病率也逐年增多。在呼吸道疾病的治疗手段中,临床干预仍以药物治疗为主。然而,全身用药存在不良反应多及全身副作用大等弊端。近年来,呼吸道吸入药物递送系统的研发为呼吸道疾病的治疗手段带来了新的变革,局部递送药物可直接作用于气道,具有起效快、疗效好且副作用小等特点,对控制气道疾病起到十分显著的效果,是一种简单、高效、安全的治疗手段,业已成为当下研究及推广的热点方向。本文就国内外关于呼吸道吸入药物递送系统的发展轨迹及最新研究进展作一简要综述,以期为临床工作者在用药的选择和应用方面提供参考借鉴。

一氧化氮治疗仪及其应用进展

一氧化氮吸入治疗作为一种新兴的医疗技术,其科学研究与临床应用依赖于一氧化氮治疗仪的发展。本文简述了一氧化氮治疗仪的研究进展。首先详细说明了一氧化氮治疗仪的类型,将其分为呼吸机联用式、呼吸机一体式及独立便携式三大类,然后分别简单介绍了三者各自的优缺点,并以临床上应用最广泛的联用式一氧化氮治疗仪为例,分析了其原理与结构,着重介绍其监测系统与净化系统。另外对目前市场上比较典型的一氧化氮治疗仪的关键技术参数进行了比较,最后探讨了一氧化氮治疗仪的当前问题及发展趋势。