Drug design and delivery最新文献

In-silico drug design: An approach which revolutionarised the drug discovery process 计算机药物设计:一种彻底改变药物发现过程的方法

Drug design and delivery Pub Date : 2013-09-01 DOI: 10.13172/2054-4057-1-1-1119

Abdul Wadood, N. Ahmed, L. Shah, Ashfaq Ahmad, Hammad Hassan, Sulaiman Shams

{"title":"In-silico drug design: An approach which revolutionarised the drug discovery process","authors":"Abdul Wadood, N. Ahmed, L. Shah, Ashfaq Ahmad, Hammad Hassan, Sulaiman Shams","doi":"10.13172/2054-4057-1-1-1119","DOIUrl":"https://doi.org/10.13172/2054-4057-1-1-1119","url":null,"abstract":"Introduction Drug discovery and development is an intense, lengthy and an interdisciplinary venture. Recently, a trend towards the use of in-silico chemistry and molecular modelling for computer-aided drug design has gained significant momentum. Insilico drug design skills are used in nanotechnology, molecular biology, biochemistry etc. The main benefit of the in-silico drug design is cost effective in research and development of drugs. There are wide ranges of software that are used in in-silico drug design, Grid computing, window based general PBPK/PD modelling software, PKUDDS for structure based drug design, APIS, JAVA, Perl and Python, in-silico drug design as well as software including software libraries. There are different techniques used in in-silico drug design visualization, homology, molecular dynamic, energy minimization molecular docking and QSAR etc. In-silico drug design can take part considerably in all stages of drug development from the preclinical discovery stage to late stage clinical development. Its exploitation in drug development helps in the selection of only a potent lead molecule and may thus thwart the late stage clinical failures; thereby a major diminution in cost can be achieved. This article gives an insight into all the aspects of in-silico drug design; its potential, drivers, current development and the future prospects. Conclusion In-silico methods have been of great importance in target identification and in prediction of novel drugs. Introduction Drug discovery and development is a very complicated, time consuming process and there are many factors responsible for the failure of different drugs such as lack of effectiveness, side effects, poor pharmacokinetics, and marketable reasons. The expenditure of this process has amplified ominously during the past thirty-four years. The Pharmaceutical Manufacturer’s Association received the industry average reports which have shown that the expenditure of drug development has enlarged from $4 million in 1962 to over $350 million in 1996. The improvement time of a drug from the first synthesis to its foreword in the market, has almost multiplied between 1960 and 1980. It has kept on comparatively unaffected since 1980 with a present time period of 9-13 years.1,4 According to pharmaceutical research and manufacturers the estimated cost of the complete drug discovery process is about US$880 million and takes up to 14 years from initial research stage to the successful marketing of an new drug in 2001.4 The recent figures of DiMasi at the Tufts Centre for Study of Drug Development (CSDD) is about US$802 million spread over 12 years, which was reported in 2003,4 while the Boston Consulting Group estimates the cost as $880 million over 15 years. At present the cost involved in the drug discovery process ranges f rom $800 million to $1.8 billion,5 The establishment of the Computer-Aided Drug Design (CADD) Centre was to endorse joint research among the scientists of various f","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78913798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 83

Microscopy characterisation of micro- and nanosystems for pharmaceutical use 医药用微纳米系统的显微表征

Drug design and delivery Pub Date : 2013-08-01 DOI: 10.13172/2054-4057-1-1-620

E. Esposito, M. Drechsler, R. Cortesi

{"title":"Microscopy characterisation of micro- and nanosystems for pharmaceutical use","authors":"E. Esposito, M. Drechsler, R. Cortesi","doi":"10.13172/2054-4057-1-1-620","DOIUrl":"https://doi.org/10.13172/2054-4057-1-1-620","url":null,"abstract":"technique for characterising microparticles and nanosystems recently developed by our research group. In particular, polyester or acrylic polymer microparticles for fenretinide administration are presented here. Moreover, with regard to nanosystems, solid lipid nanoparticles, nanostructured lipid carriers for prednisone and clotrimazole administration and monooleine aqueous dispersion are discussed. Methodology Microparticles were produced by the ‘solvent evaporation method’. Solid lipid nanoparticlesand nanostructured lipid carriers were prepared by stirring, followed by ultrasonication. Monooleine aqueous dispersionswere produced by the hydrotrope or by the hot homogenization methods. For scanning electron microscopyanalysis, microparticles were metallized by gold coating (Edwards Sputter coat-ing S150) and visualized at 15 – 20 kV with a 360 Stereoscan (Cambridge Instruments, Cambridge, UK). For Cryo-TEM analysis sampleswere vitrified and transferred to a Zeiss EM922Omega (Zeiss SMT, Oberkochen, Germany). Images were recorded by a CCD digital camera (Ultrascan 1000, Gatan) and analyzed using a GMS 1.8 software (Gatan). Conclusion Microscopy is to be considered as an indispensable tool to study drug delivery systems. In particular, scanning electron microscopy is helpful in giving information about micro-sized powders, allowing to identify microspheres and microcapsules, as well as to obtain size distribution of the observed particles. Introduction Microand nanoparticles have attracted pharmaceutical interest in the last decades since they offer a number of advantages with respect to other delivery systems such as: (a) the ability to maintain unaltered physicochemical characteristics for long periods allowing long-term storage; (b) the possible administration through different ways (oral, intramuscular or subcutaneous) depending on their composition and (c) their suitability for industrial production1. Concerning nanosystems, lipid dispersions possess a potential use as matrixes able to dissolve and deliver active molecules in a controlled fashion, thereby improving their bioavailability and reducing side-effects2. In particular, solid lipid nanoparticles (SLN) are delivery systems in which the nano-dispersed phase has a matrix of crystalline solid lipids. SLN are able to protect encapsulated molecules from degradation and modulate their release3,4. Another generation of SLN is represented by nanostructured lipid carriers (NLC) whose matrix is composed of a mixture of solid–liquid lipids able to better solubilise lipophilic drugs5,6. Another type of lipid dispersion able to provide matrices for sustained drug release is typified by monooleine aqueous dispersions (MAD). MAD are heterogeneous systems generated by the dispersion of an amphiphilic lipid, such as monoolein, in water. They are constituted of complex lyotropic liquid crystalline nanostructures like micellar, lamellar, hexagonal and cubic phases, the predominance of one spe","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79227113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Insoluble drug delivery technologies: review of health benefits and business potentials 不溶性给药技术:健康效益和商业潜力综述

Drug design and delivery Pub Date : 2013-08-01 DOI: 10.13172/2054-4057-1-1-619

B. Siddalingappa, V. Nekkanti, G. Betageri

引用次数: 12

Synthesis of the diastereomers of 5-(2,2-dichlorocyclopropyl)- and 5-(2-chlorocyclopropyl)-2'-deoxyuridine, and the antiviral and cytotoxic activity of these and bromo analogues. 5-(2,2-二氯环丙基)-和5-(2-氯环丙基)-2'-脱氧尿苷非对映体的合成及其与溴类似物的抗病毒和细胞毒活性。