在药物早期临床研究中加速器质谱的应用研究现状

加速器质谱(AMS)是一种超灵敏同位素分析技术,近年来被广泛用于药物临床研发中14C标记药物的测定,且无需传统人体放射性研究相关的安全性试验。在药物早期临床试验阶段,加速器质谱有利于开展微剂量及微量示踪研究,从而尽早获得药物药代动力学及代谢特征,包括基本药代动力学参数(清除率、表观分布容积)、绝对生物利用度、物料平衡和消除途径等。本文就AMS的研究进展及其在药物早期临床研究中的应用做一综述。     

Recent advances in flavivirus antiviral drug discovery and vaccine development

Many flaviviruses, including yellow fever virus, dengue virus, Japanese encephalitis virus, tick-borne encephalitis virus, and West Nile virus, are globally important human pathogens. Despite an emergence and resurgence of flavivirus-mediated disease, specific therapies are not yet available; however, significant progress has been made toward the prevention and treatment of flavivirus infections. In this article we review recent advances made in the areas of (i) flavivirus vaccine development, and (ii) antiflavivirus drug discovery reported in literature and patents, and highlight strategies used in these investigations.     

Recent advances in bioreductive drug targeting

Advances in the chemistry of bioreductive drug activation have led to the design of hypoxia-selective drug delivery systems. These prodrugs, comprising a bioreductive "trigger", "linker" and "effector" were first explored with nitrobenzyl quaternary ammonium mustards. Alternative nitroheterocycles were subsequently developed, together with new avenues of prodrug activation in ADEPT and GDEPT. Major advances have also been made in utilising indolequinone reductive chemistry based upon an appreciation of the kinetics of oxygen-sensitive reductive elimination.     

Recent advances in ophthalmic drug delivery

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert (-6 months), Retisert (-3 years) and Iluvien (-3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems.     

Recent advances in transdermal drug delivery

Transdermal delivery of pharmacologically active agents has been extensively studied for the past 40 years. Despite the strong efforts, currently, only about 40 products are in market on about 20 drug molecules, due to the requirements that the patch area should be small enough for the patients to feel comfortable, and to the barrier properties of the stratum corneum. Various approaches to overcome the barrier function of skin through physical and chemical means have been broadly studied. The development of an effective transdermal delivery system is dictated by the unique physicochemical property each drug molecule possesses. In this review, we have summarized various physical and chemical approaches for transdermal flux enhancement, including the application of electricity, ultrasound, microneedle and chemical enhancers. Pressure sensitive adhesive such as acrylics, rubbers and silicones are described together with recent developments. Factors affecting dosage form design, particularly for drug in adhesive system, like adhesion and crystallization are also discussed.     

Recent advances in malaria drug discovery

Malaria is responsible for over 300 million clinical cases annually and claims the lives of approximately 1-2 million. With a disease that has plagued humanity throughout history, one would think that better control measures would be in place to decrease the mortality and morbidity associated with malaria. Due to malaria drug resistance, an increase in the number of clinical infections and deaths is soon likely to be observed. Therefore, there is a push to identify and introduce new drug entities for malaria treatment and prophylaxis. In an effort to develop new malaria drugs, several different approaches have been implemented. These include the use of drug combinations of either new or existing antimalarials, exploitation of natural products, identification of resistance reversal or sensitizing agents and the targeting of specific malarial enzymes. Past experience has shown that introduction of the same chemical entities, such as quinolines and antifolates, results in only limited efficacy with resistance developing rapidly within one year of introduction. New approaches to drug discovery should identify novel chemotypes which circumvent the parasite's disposition to drug resistance. This review summarizes current efforts in malaria drug discovery as uncovered in recent patent literature.     

Recent advances in immunoinformatics: application of in silico tools to drug development

Immunoinformatics is an emerging specialization of bioinformatics that focuses upon the structure, function and interactions of the molecules involved in immunity. Two major cell types, T-cells and B-cells, play significant roles in allergy, inflammation, infection and protective immunity. This review examines recently developed in silico tools and databases that can be used to identify, characterize or predict antigen epitopes recognized by T- and B-cells including the latest generation of B-cell epitope prediction tools that employ peptide-binding information derived from peptide phage display experiments. The application of these tools to facilitate drug development efforts is also discussed.     

Recent advances in computer-aided drug design methods

A number of computational advances have had significant impact on the field of computer-aided drug design over the last several years. These advances can be grouped into three basic areas: conformational modelling (of small molecules, macromolecules and their complexes), property modelling (of physical, biological and chemical properties) and molecular design (to optimise physical, biological or chemical properties). The current state of the art in each of these areas is introduced. Recent patents related to these three topics are critically reviewed and their impact on the field of computer-aided drug design is assessed.     

Recent advances in intraocular drug delivery systems

Vitreoretinal diseases are refractory to both topical and systemic pharmacological approaches because of specific environment of the eye. That is, the cornea, the sclera, nasolacrimal drainage of tears, frontward stream of aqueous humor, blood-aqueous barrier, and blood-retinal barrier strictly limit penetration and diffusion of drug into the retina. However, recent advances in intraocular drug delivery systems (DDS) have enabled drug to be delivered effectively into the eye. Clinically successful or promising cases involve non-biodegradable implants and inserts, biodegradable inserts and microparticles, intravitreal or sub-Tenon's injection of triamcinolone acetonide, and a photodynamic therapy (PDT) with verteporfin, a photosensitizer. More recently, a variety of pharmacological challenges to treat exudative age-related macular degeneration and macular edema are proceeding into clinical trials, as soon as anti-vascular endothelial growth factor (anti-VEGF) therapies have been proved to be effective by repeated intravitreal injections. In the near future, DDS must be required not only to develop a new treatment modality but also to improve efficacy and/or reduce injection numbers of currently available drugs. Here we introduce controlled release of drug and discussion of recent patents with biodegradable or non-biodegradable implants and drug targeting by modification of systemically administered drug.     

Recent advances in electrospun for drug delivery purpose

Abstract

Electrospun, an advanced technology, has been successfully employed for fibre production and offers many merits in novel drug delivery systems (DDSs). In recent years, electrospun has gained significant attention and attraction of the scientists in soaring numbers. This technology is superior to other technologies in fabricating the fibres which range from micrometers to manometers scale. The selection of appropriate polymers, electrospun processes and electrospun parameters play important roles in controlling the drug release while, treating serious illness. Besides, electrospraying process has similar characteristics to the electrospun and is presented briefly here. Further, in vivo and in vitro evaluations of the electrospun nanofibers are comprehensively discussed. In addition, the electrospun nanotechnology has been exploited to design drug release systems, investigate drug’s pharmacokinetics and further develop DDS. The electrospun nanofibers improve bioactivity of various types of drugs including water-insoluble, soluble, anticancer and antibacterial drugs and genetic materials. In the end, the prospects and challenges in the process of designing drug-loaded electrospun nanofibers are discussed in detail.     

Recent advances in inorganic nanoparticle-based drug delivery systems

Drug delivery systems, designed to enhance drug efficacy and reduce their adverse effects, have evolved accompanied by the development of novel materials. Nanotechnology is an emerging scientific area that has created a variety of intriguing inorganic nanoparticles. In this review, we focus on the feasibility of inorganic nanoparticles, including iron oxide nanoparticles, gold nanoparticles, fullerenes and carbon nanohorns, as drug carriers, and summarize recent advances in this field.     

Recent advances in intravesical drug/gene delivery

Targeting of drugs administered systemically relies on the higher affinity of ligands for specific receptors to obtain selectivity in drug response. However, achieving the same goal inside the bladder is much easier with an intelligent pharmaceutical approach that restricts drug effects by exploiting the pelvic anatomical architecture of the human body. This regional therapy involves placement of drugs directly into the bladder through a urethral catheter. It is obvious that drug administration by this route holds advantage in chemotherapy of superficial bladder cancer, and it has now become the most widely used treatment modality for this ailment. In recent years, the intravesical route has also been exploited either as an adjunct to an oral regimen or as a second-line treatment for neurogenic bladder. (Lamm, D. L.; Griffith, J. G. Semin. Urol. 1992, 10, 39-44. Igawa, Y.; Satoh, T.; Mizusawa, H.; Seki, S.; Kato, H.; Ishizuka, O.; Nishizawa, O. BJU Int. 2003, 91, 637-641.) Instillation of DNA via this route using different vectors has been able to restrict the transgene expression in organs other than bladder. The present review article will discuss the shortcomings of the current options available for intravesical drug delivery (IDD) and lay a perspective for future developments in this field.     

心肺复苏药物治疗的新进展

传统的急救用药习惯和方法可引起许多不良反应,为了纠正这些问题,“2000心肺复苏指南”发表以来,根据循证医学的原则,对急危重症患者抢救的方法、技术、用药等进行了修订或改进。“2005心肺复苏指南”对上述问题又做出了进一步的建议。本文总结阐述了心肺复苏用药途径及常用药物使用的一些新的观念和理论,并在循证医学基础上就两个指南修改的原因进行解读,供医药同行参考。     

微乳黏膜给药系统的应用与研究进展

通过分析、整理和归纳近几年的国内外文献,介绍微乳在鼻腔、口腔、眼和阴道黏膜给药中的研究和应用进展.     

Recent in vivo advances in cell-penetrating peptide-assisted drug delivery

ABSTRACT

Introduction: Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment.

Areas covered: In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP–cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA).

Expert Opinion: Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.