现代制剂技术与药物释放系统

<正> 从古至今,常规制剂技术已为人类提供了几十种常规剂型;现代制剂技术则能设计出逐步完善的、能改变药物释放时间和速率的新剂型,以达到常规剂型所达不到的、人们期望的治疗目的,并能提高患者使用的顺应性。这类新剂型统称为药物释放系统(Drug Delievery System DDS),其定义为集中制剂新技术(膜控释技术、徽囊、徽球、脂质体、前体药物、包封细胞等)而设计的各种给药方式的总称。其重点在     

脂质体药物释放系统的最新进展

近年来脂质体药物释放系统技术已步入成熟期，目前有几种脂质体药物已处於临床后期考核或已进入市场。许多临床前和临床研究表明，药物（如抗肿瘤药）经脂质体包裹后毒性减弱，但效力仍保持甚至提高。其部分原因是由于改变了药物动力学，使药物在病灶部位（如肿瘤）累积，减少了在敏感组织的分布。正在研制的融合性脂质体系统具有胞内释放药物的能力，预期可提高治疗效果。脂质体设计方面的进展使其在释放新的生物技术产品（如重组蛋     

药物释放系统的发展

本文论述了口服缓释控释给药系统、靶向给药系统、透皮给药系统、粘膜给药系统和新型给药系统的概况,从中可看出给药系统的发展趋势。     

脂质体药物释放系统的最新进展

近年来脂质体药物释放系统技术已步入成熟期,目前有几种脂质体药物已处於临床后期考核或已进入市场。许多临床前和临床研究表明,药物(如抗肿瘤药)经脂质体包裹后毒性减弱,但效力仍保持甚至提高。其部分原因是由于改变了药物动力学,使药物在病灶部位(如肿瘤)累积,减少了在敏感组织的分布。正在研制的融合性脂质体系统具有胞内释放药物的能力,预期可提高治疗效果。脂质体设计方面的进展使其在释放新的生物技术产品(如重组蛋白、反义寡核苷酸和克隆基因)方面有了新的应用。     

靶向药物释放系统的定量评价

本文回顾了评价靶向药物释放系统的方法，到在多数情况下，通常采用的参数不一定能为被试的药物释放系统和常规药物释放系统提供真实的定量评价，证明数据收集不当可能对药物释放系统产生错误的评价，推荐了一些数学方程式，借助于动物静注正定霉素和阿霉素的溶液和脂质体后药物在体内配置的数据，验证它们的用途。     

药物纳米混悬剂释放系统

40％以上的候选药物水溶性差,常使一些重要的候选药物不能上市或使一些药品不能充分发挥疗效。据估计,全球每年约有650亿美元的药品因生物利用度差,造成病人花费大、疗效小,尤应注意的是有的药物出现严重毒性或甚至有致命的危险。纳米技术可克服这些缺点,并且日益受人关注。     

药物释放系统的发展

本文论述了口服缓释控释给药系统、靶向给药系统、透皮给药系统、粘膜给药系统和新型给药系统的概况,从中可看出给药系统的发展趋势。     

缓控释系统药物释放的数学模型研究进展

目的概括各类骨架型缓控释系统的药物释放数学模型研究进展。方法对整块骨架系统、溶蚀型骨架系统和溶胀型骨架系统的药物释放数学方程进行阐述，同时根据其释药原理的不同进行划分和比较。结果为今后缓控释给药系统的深入研究提供了科学依据。结论目前的数学模型无法完全模拟药物从骨架中释放的实际情况，应建立更切合实际的模型。     

国内外药物释放系统研究的文献计量学分析

利用互联网Medline数据库、清华全文数据库、欧洲专利数据库和中国知识产权局专利数据库,应用统计和情报分析的方法,对国内外近年来发表的有关药物释放系统(DDS)主题文献的论文进行文献数量、年代及研究内容的统计分析,同时对国内外药物制剂专利公布情况进行资料统计,对比分析国内外DDS的研究领域、研究重点变化及发展趋势,探讨我国未来DDS的研究重点与发展前景。     

我国药物释放系统的主要研发机构及相关政策分析

药物释放系统（Drug Delivery Systems，DDS）又称给药系统、药物传输系统、药物投递系统，系指人们在防治疾病的过程中所采用的各种治疗药物的不同给药形式。中国医药领域需要新药但研发能力却受制于经费的短缺，如使用DDS技术有助于对即将到期的专利药进行创新从而进一步延长其专利占有期，可以缩短药品研发周期，提高我国在全球医药市场中的竞争力。通过对我国药物释放系统研究的相关政策分析及主要研发机构的研究领域、研究重点和学科带头人情况的情报调研，分析国家对药学和药剂学的资助及政策支持情况，阐明我国药物释放系统研究的重点领域和取得的成就。     

药物剂型和药物传输系统的发展综述

近年来,现代药剂学发展迅速,新剂型和药物传输系统展现了广阔的发展前景。发展新剂型和新给药系统可以获得短期内成效,使药品差异化,提高制药企业研发及产业化水平。在有限的资源分配下,我国唯有发展制剂创新才能缩小同发达国家的差距。本文就现代药剂学的发展进行综述,重点探讨剂型和给药系统的相关理论和应用,介绍了药剂学的最新研究进展,并总结未来发展可能遇到的挑战和机遇。     

Biomedical microelectromechanical systems (BioMEMS): Revolution in drug delivery and analytical techniques

Advancement in microelectromechanical system has facilitated the microfabrication of polymeric substrates and the development of the novel class of controlled drug delivery devices. These vehicles have specifically tailored three dimensional physical and chemical features which together, provide the capacity to target cell, stimulate unidirectional controlled release of therapeutics and augment permeation across the barriers. Apart from drug delivery devices microfabrication technology’s offer exciting prospects to generate biomimetic gastrointestinal tract models. BioMEMS are capable of analysing biochemical liquid sample like solution of metabolites, macromolecules, proteins, nucleic acid, cells and viruses. This review summarized multidisciplinary application of biomedical microelectromechanical systems in drug delivery and its potential in analytical procedures.     

渗透泵药物传递系统制备技术研究进展

渗透泵药物传递系统由于能够平稳的释放药物,且释药不易受药物的理化性质、病人生理因素及摄入食物的影响,日益受到药学工作者的关注.目前,已经上市销售的渗透泵片数目对比10年前增长了近1倍.该文简述了渗透泵药物传递系统的结构分类、详细介绍了口服渗透泵制备技术近年来的研究进展.     

Development of novel drug delivery system (DDS) technologies for proteomic-based drug development

With the success of human genome projects, the focus of life science research has shifted to the functional and structural analyses of proteins, such as disease proteomics. These structural and functional analyses of expressed proteins in the cells and/or tissues are expected to contribute to the identification of therapeutically applicable proteins for various diseases. Thus, pharmaco-proteomic based drug development for protein therapies is most noticed currently. However, there is a clinical difficulty to use almost bioactive proteins, because of their very low stability and pleiotropic actions in vivo. To promote pharmaco-proteomic based drug development for protein therapies to various diseases, we have attempted to establish a system for creating functional mutant proteins (muteins) with desired properties, and to develop a site-specific polymer-conjugation system for further improving the therapeutic potency of proteins. In this review, we are introducing our original protein-drug innovation systems mentioned above.     

Pharmacokinetics of cefazolin administered as a new drug delivery system in healthy volunteers

A study was made of the pharmacokinetic behaviour in plasma and urine of cefazolin in seven healthy volunteers following parenteral administration of sodium cefazolin (1250 mg) and a sustained release formulation containing sodium cefazolin: cefazolin-dibenzylamine (1:4) at a total dose of 1250 mg, both formulations being administered over 1 week by the i.m. route. Cefazolin concentrations in plasma and urine were determined by a HPLC technique. Kinetic analysis of the experimental results was performed using an open single-compartment kinetic model and a sustained release model for the drug administered as standard formulation and the sustained release formulation, respectively. The results obtained point to significant variations in the pharmacokinetic profile of the drug when administered in the DDS. The time of cefazolin at levels greater than 1 microgram ml-1 was 16.03 +/- 2.51 and 47.76 +/- 14.18 h-1 after administration of the standard formulation and the DDS, respectively. The urinary excretion rate curves also show the existence of sustained drug levels in the urine following administration of the DDS. The renal clearance of the drug did not show statistically significant differences between the two formulations administered. The process of release of cefazolin from the cefazolin-dibenzylamine complex proved to be a first order kinetic process. The release constant of the antibiotic was calculated according to three different methods: the Wagner-Nelson method; the statistical moments method; and the fitting of the plasma levels curves to a compartmental model considering release and absorption. The values obtained for this constant ranges from 0.026 +/- 0.02 h-1 calculated with the method of statistical moments to 0.094 +/- 0.03 h-1 as calculated by the equation derived for the plasma fitting of cefazolin administered as DDS.     

Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies

NLCs have provoked the incessant impulsion for the development of safe and valuable drug delivery systems owing to their exceptional physicochemical and then biocompatible characteristics. Throughout the earlier period, a lot of studies recounting NLCs based formulations have been noticeably increased. They are binary system which contains both solid and liquid lipids aiming to produce less ordered lipidic core. Their constituents particularly influence the physicochemical properties and effectiveness of the final product. NLCs can be fabricated by different techniques which are classified according to consumed energy. More utilization NLCs is essential due to overcome barriers surrounded by the technological procedure of lipid-based nanocarriers’ formulation and increased information of the core mechanisms of their transport via various routes of administration. They can be used in different applications and by different routes such as oral, cutaneous, ocular and pulmonary. This review article seeks to present an overview on the existing situation of the art of NLCs for future clinics through exposition of their applications which shall foster their lucid use. The reported records evidently demonstrate the promise of NLCs for innovate therapeutic applications in the future.     

口服结肠定位给药系统

综述了近年来口服结肠定位给药系统的发展状况 ,并评价了各类结肠定位给药系统的优、缺点和发展前景     

Trimodal synergistic antitumor drug delivery system based on graphene oxide

A multifunctional antitumor drug delivery system was synthesized based on graphene oxide (GO) for near-infrared (NIR) light controlling chemotherapeutic/photothermal (PTT) /photodynamic (PDT) trimodal synergistic therapy. The system named ICG-Wed-GO was formed by co-loading wedelolactone (Wed) and indocyanine green (ICG) on the surface of GO through π–π stacking interaction. Under NIR laser irradiation, ICG-Wed-GO could effectively absorb and transform optical energy to heat, generate reactive oxygen species (ROS) to ablating and damage tumor cells. The temperature of ICG-Wed-GO solution reached up to 79.4?°C in 10?min with NIR irradiation. In in vitro and in vivo study, ICG-Wed-GO showed excellent antitumor effect. After 14-day treatment of ICG-Wed-GO with NIR laser irradiation, the tumor disappeared completely on tumor-bearing mice. The low biotoxicity of ICG-Wed-GO was also proved. The system achieved the synergistic trimodal chemotherapeutic/photothermal/photodynamic treatment and demonstrated excellent antitumor effect, which is expected to have a greater potential for cancer therapy.     

Ultrasonic gene and drug delivery to the cardiovascular system

Ultrasound targeted microbubble destruction has evolved as a promising tool for organ specific gene and drug delivery. This technique has initially been developed as a method in myocardial contrast echocardiography, destroying intramyocardial microbubbles to characterize refill kinetics. When loading similar microbubbles with a bioactive substance, ultrasonic destruction of microbubbles may release the transported substance in the targeted organ. Furthermore, high amplitude oscillations of microbubbles lead to increased capillary and cell membrane permeability, thus facilitating tissue and cell penetration of the released substance. While this technique has been successfully used in many organs, its application in the cardiovascular system has dominated so far. Drug delivery using microbubbles has played a minor role in the cardiovascular system. In contrast, gene transfer has been successfully achieved in many studies. Both viral and non-viral vectors were used for loading on microbubbles. This review article will give an overview on studies that have applied ultrasound targeted microbubble destruction to deliver substances in the heart and blood vessels. It will show potential therapeutic targets, especially for gene therapy, describe feasible substances that can be loaded on microbubbles, and critically discuss prospects and limitations of this technique.