Abstract：
:Long-acting drug nanosuspension formulations are coming to the fore as controlled release strategies for several medical conditions and as a preventative measure against HIV infection. However, such delivery systems must, by necessity, be given by hypodermic injection, typically into muscle. This poses problems for patients who are needle-phobic, given that injections have to be administered on a weekly or monthly basis. Needle-stick injuries, inappropriate reuse of needles, and poor disposal practices are major challenges in developing countries. Dissolving microneedles (MNs) are capable of delivering high drug doses, if suitably designed and formulated, and are also capable of delivering nanoparticles (NPs) into viable skin. Given that such microneedles are minimally invasive and self-disabling, the potential for major enhancement in patient care and compliance exists. In this review, we explore the key considerations in the development of these combination drug delivery systems.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Donnelly RF,Larrañeta Edoi
10.1016/j.drudis.2017.10.013subject
Has Abstractpub_date
2018-05-01 00:00:00pages
1026-1033issue
5eissn
1359-6446issn
1878-5832pii
S1359-6446(17)30233-7journal_volume
23pub_type
杂志文章,评审abstract：:When cross-reactivity of a lead antibody across species is limited, antibody development programs require the generation of surrogate molecules or surrogate animal models necessary for the conduct of preclinical pharmacology and safety studies. When surrogate approaches are employed, the complexities and challenges fo...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.09.014
更新日期：2009-12-01 00:00:00
abstract：:Recent groundbreaking work in genetics has identified thousands of small-effect genetic variants throughout the genome that are associated with almost all major diseases. These genome-wide association studies (GWAS) are often proposed as a source of future medical breakthroughs. However, with several notable exception...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2015.05.012
更新日期：2015-10-01 00:00:00
abstract：:There is a continuing need to hasten and improve protein-ligand docking to facilitate the next generation of drug discovery. As the drug-like chemical space reaches into the billions of molecules, increasingly powerful computer systems are required to probe, as well as tackle, the software engineering challenges neede...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.023
更新日期：2016-10-01 00:00:00
abstract：:The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendoth...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.05.017
更新日期：2016-10-01 00:00:00
abstract：:Magnetic nanoparticles (MNPs) play a vital role for improved imaging applications. Recently, a number of studies demonstrate MNPs can be applied for targeted delivery, sustained release of therapeutics, and hyperthermia. Based on stable particle size and shape, biocompatibility, and inherent contrast enhancement chara...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.018
更新日期：2017-08-01 00:00:00
abstract：:Drugs that covalently bond to their biological targets have a long history in drug discovery. A look at drug approvals in recent years suggests that covalent drugs will continue to make impacts on human health for years to come. Although fraught with concerns about toxicity, the high potencies and prolonged effects ac...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.05.005
更新日期：2015-09-01 00:00:00
abstract：:Pulmonary arterial hypertension (PAH) is a progressive disease that involves pathological remodeling, vasoconstriction and thrombosis. Alterations in hemostasis, coagulation and platelet activation are consistently observed in PAH patients. Microparticles derived from platelets, inflammatory cells and the endothelium ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.04.001
更新日期：2014-08-01 00:00:00
abstract：:Atomic force microscopy is being used ever more widely in biological imaging, because of its unique ability to provide structural information at the single molecule level and under near-physiological conditions. Detailed topographic images of potential drug targets, such as proteins and DNA, have been produced, and th...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(03)02905-2
更新日期：2004-01-15 00:00:00
abstract：:Fetal hypoxia adversely affects the brain and heart development, yet the mechanisms responsible remain elusive. Recent studies indicate an important role of the extracellular matrix in fetal development and tissue remodeling. The matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of me...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.09.011
更新日期：2012-02-01 00:00:00
abstract：:Natural products have been the single most productive source of leads for the development of drugs. Over a 100 new products are in clinical development, particularly as anti-cancer agents and anti-infectives. Application of molecular biological techniques is increasing the availability of novel compounds that can be c...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.07.004
更新日期：2008-10-01 00:00:00
abstract：:This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry as many new approaches to the design of innovative metal-based anticancer drugs are emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.09.003
更新日期：2009-12-01 00:00:00
abstract：:The potential of peptide and protein anticancer agents has yet to be realized owing to the many unresolved problems concerning their delivery to the site of a tumor and into tumor cells. However, our understanding of the mechanisms underlying the biological fate and biodistribution of protein and peptide drugs has adv...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(03)02623-0
更新日期：2003-03-15 00:00:00
abstract：:Following multiple warnings from governments and health organisations, there has been renewed investment, led by the public sector, in the discovery of novel antimicrobials to meet the challenge of rising levels of drug-resistant infection, particularly in the case of resistance to antibiotics. Initiatives have also b...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.11.015
更新日期：2019-02-01 00:00:00
abstract：:The unique anti-atherosclerosis abilities and other cardioprotective properties make high-density lipoprotein (HDL) a promising solution in treating cardiovascular diseases. A number of studies showed that HDL-based therapy was well tolerated and has great potential in the future. Among all these new agents, the most ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.08.010
更新日期：2017-01-01 00:00:00
abstract：:There is currently a marketed drug for nearly every nuclear receptor for which the natural ligand has been identified. However, because of the complexity of signal transduction by this class of ligand-regulated transcription factors, few of these drugs have been optimized for pharmaceutical effectiveness. Over the pas...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03201-5
更新日期：2004-09-01 00:00:00
abstract：:Lack of predictability of clinical efficacy and safety is an important problem facing pharmaceutical research today. Translational PK-PD has the ability to integrate data generated from diverse test platforms during discovery and development in a mechanistic framework. Therefore, successful implementation of translati...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.002
更新日期：2007-12-01 00:00:00
abstract：:Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The trea...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.05.016
更新日期：2017-08-01 00:00:00
abstract：:Current multiparameter optimization (MPO) strategies make use of few experimental physicochemical descriptors (i.e., solubility at physiological pH and lipophilicity in the octanol/water system). Here, we show how new trends in drug discovery (i.e., large and flexible molecules for 'difficult' targets) call for the in...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.11.017
更新日期：2017-06-01 00:00:00
abstract：:Options for disease-modifying therapies in multiple sclerosis have increased over the past two decades. Among these innovations are interferon-β, glatiramer acetate, fumaric acid and dihydroorotate dehydrogenase inhibitors, an antibody targeting the migration of immune cells, a compound that traps immune cells in lymp...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.11.022
更新日期：2020-11-25 00:00:00
abstract：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(00)01674-3
更新日期：2001-03-01 00:00:00
abstract：:The tumor vasculature transports oxygen, nutrients and drugs for crucial roles in tumor therapy. Antivascular therapy directly targets existing tumor vessels to reduce blood perfusion and then inhibit tumor growth. Vascular disrupting agents and ultrasound-stimulated microbubble destruction use chemical toxicity and p...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.06.001
更新日期：2017-10-01 00:00:00
abstract：:Gastric bypass surgery is effectively a polypharmacological approach for treatment of obesity, type 2 diabetes and nonalcoholic steatohepatitis (NASH). The gastric bypass mimetic approaches reviewed are fixed-dose combinatorial pharmacological approaches. There are two key concepts incorporated into these gastric bypa...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.009
更新日期：2017-08-01 00:00:00
abstract：:For drug discovery, historical experience is always of significance. Through examining the history of traditional medicines, we find that these medicines have more implications for drug discovery than just providing new chemical entities. The history of traditional medicines indicates that they depended more on the co...
journal_title：Drug discovery today
pub_type： 历史文章,杂志文章
doi：10.1016/j.drudis.2008.07.002
更新日期：2009-02-01 00:00:00
abstract：:Drug-delivery technologies for modified drug release have been in existence for decades, but their utilization has been largely limited to post-launch efforts improving therapeutic outcomes. Recently, they have gained renewed importance because the pharmaceutical industry is steadily shifting to a more integrated disc...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.12.008
更新日期：2020-12-14 00:00:00
abstract：:The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer appro...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.07.024
更新日期：2007-10-01 00:00:00
abstract：:Cocaine is a major drug of abuse whose devastating effects have captured the attention of health officials and policy makers. Based upon the alarming health and crime-related costs associated with the use of this powerful reinforcing drug, immediate therapies are needed for the treatment of cocaine addiction. In this ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(99)01332-x
更新日期：1999-07-01 00:00:00
abstract：:Described in this article are strategies implemented to increase the throughput of in vivo rodent pharmacokinetic (PK) studies using the snapshot PK study design and automated methods for compound submission, sample processing, data analysis and reporting. Applying snapshot PK studies to categorize the oral exposure o...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.014
更新日期：2008-04-01 00:00:00
abstract：:Cervical cancer is the fourth most common cancer among women worldwide and its development is mainly associated with human papillomavirus infection, a highly sexually transmissible virus. The expression of E6 and E7 viral oncoproteins deregulates cell repairing mechanisms through impairment of tumor suppressor protein...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.07.011
更新日期：2019-10-01 00:00:00
abstract：:The blood-brain barrier (BBB) hinders the accumulation of active compounds in the central nervous system, thus decreasing their therapeutic effectiveness. To overcome this obstacle, interesting supramolecular nanodevices are herein considered. These systems have many advantages over the conventional formulations, such...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.02.006
更新日期：2011-04-01 00:00:00
abstract：:The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologi...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.02.006
更新日期：2008-07-01 00:00:00
