25 research outputs found
Structure-property correlations in piracetam polytypes
Polymorphs II and III of piracetam exhibit a polytypic relationship comprising identical layers of molecules with different relative arrangements. Polymorph II has an interlayer structure in which the piracetam molecules adopt face-to-face and edge-to-edge alignments, while polymorph III adopts a herringbone type arrangement in the interlayer region. The structures are analysed using energy-vector models derived from PIXEL pairwise intermolecular interaction energies. Thermal expansion measurements show that the principal expansion axes are approximately aligned with the unit-cell axes in polymorph III, corresponding to directions within the polytypic layers and perpendicular to them. Expansion perpendicular to the layers is almost twice as large as that along any direction within the layers. Polymorph II shows greater volumetric expansion than polymorph III, and its principal expansion axes are aligned parallel and perpendicular to the planes of the piracetam molecules, rather than along the unit-cell axes. Nanoindentation experiments performed on single crystals along the direction perpendicular to the polytypic layers show that the polymorphs have similar hardness (H) values, but polymorph III has a significantly larger elastic modulus (E). Along the direction nearly parallel to the polytypic layers, polymorph II shows a very similar E value to that perpendicular to the layers, but a significantly smaller H value, implying easier slip between the polytypic layers. The tableting behaviour of bulk polymorph II is superior to that of polymorph III, suggesting greater plasticity for polymorph II, which is likely due to a greater degree of slip.We are grateful to the Danish Council for Independent Research | Natural Sciences (DFF-1323-00122), and to the Department of Pharmacy, University of Copenhagen, for funding this wor
Subcellular Mass Spectrometry Imaging and Absolute Quantitative Analysis across Organelles
Mass spectrometry imaging is a field that promises to become a mainstream bioanalysis technology by allowing the combination of single-cell imaging and subcellular quantitative analysis. The frontier of single-cell imaging has advanced to the point where it is now possible to compare the chemical contents of individual organelles in terms of raw or normalized ion signal. However, to realize the full potential of this technology, it is necessary to move beyond this concept of relative quantification. Here we present a nanoSIMS imaging method that directly measures the absolute concentration of an organelle-associated, isotopically labeled, pro-drug directly from a mass spectrometry image. This is validated with a recently developed nanoelectrochemistry method for single organelles. We establish a limit of detection based on the number of isotopic labels used and the volume of the organelle of interest, also offering this calculation as a web application. This approach allows subcellular quantification of drugs and metabolites, an overarching and previously unmet goal in cell science and pharmaceutical development
Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens
TITLE:A REVIEW ON NANOPARTICLES: TINY SOLDIERS FOR GIANT TUMORS
ABSTRACTNanoparticles as drug delivery systems enable unique approaches for cancer treatment. Cancer is a leading cause of deaths. Millions of people are diagnosed with cancer every year. Owing to the development of nanotechnology and biotechnology, nanoparticles of biodegradable polymers as effective drug delivery systems have received significant attention. They have the ability to carry various therapeutic agents including anticancer drugs, DNA, peptides and proteins. Over the past decade, there has been an increasing interest in using nanotechnology for cancer therapy. The development of smart targeted nanoparticles that can deliver drugs at a sustained rate directly to cancer cells may provide better efficacy and lower toxicity for treating primary and advanced metastatic tumors. Thus metastatic cancer can also treated by nanoparticles. Recently, albumin based nanoparticles have received much attention by the researchers owing to its biodegradability, biocompatibility and the ability to deliver a wide range of drugs. Â This review explores recent work directed towards more targeted treatment of cancer. Treatment opportunities using Nanoparticles-targeted therapies are summarized. In this review, we will review the available nanoparticle technology platforms and their impact for cancer therapy along with Nano economics, future products and patents on nanoparticles.KEYWORDS: Cancer, Nanoparticles, Drug delivery, Targeted Metastatic cancer
Direct and enhanced delivery of nanoliposomes of anti schizophrenic agent to the brain through nasal route
The problem of inadequate oral bioavailability of Quetiapine Fumarate, a lipophilic drug used for schizophrenia, due to hepatic metabolism and repulsion by brain barrier was attempted in this study. Combination of two approaches, viz. Quetiapine inclusion into the liposomal carrier for better diffusion and administration through nasal route to avoid hepatic metabolism and barrier elimination was applied. Thin film hydration followed by sonication method was employed in liposome preparation and the formulation was optimized using 32 full factorial design. The number of sonication cycles (X1) of 2 min and 80% amplitude and molar ratio of constructional components such as cholesterol to egg phosphatidylcholine (X2) as independent variables and a % of entrapment efficiency (Y1) and cumulative in vitro drug release (Y2) at 6 h as dependent variables was selected. Batch F7 prepared by 2 cycles of sonication and 1:3 M ratio of cholesterol:egg phosphatidylcholine was optimized as a consequence of substantial entrapment efficiency of 75.63 ± 3.77%, and 99.92 ± 1.88% drug release and 32.33 ± 1.53% drug diffusion, which was optimum among all other batches at 6 h. Diffusion study was done for all the batches of liposomal formulation by using sheep nasal mucosa and good amount with better diffusion rate was measured which proved liposomal dispersion a virtuous delivery system for brain drug delivery through nasal route. Results of in vivo, ciliotoxicity and gamma scintigraphy studies on mice supported the above inference
Relating the tableting behavior of piroxicam polytypes to their crystal structures using energy-vector models
Estimating relative stability of polymorphs by generation of configurational free energy phase diagram
Early assessment of bulk powder processability as a part of solid form screening
A systematic assessment of key material attributes of active pharmaceutical ingredients (APIs) using minimal material approach is illustrated at the particulate level and bulk level. At a bulk level, flowability improvement of an API through crystal habit manipulation is exemplified. The impact of crystal structures and particulate properties (crystal habit and crystal size) on their mechanical behaviour were addressed by measuring powder tabletability. Bulk powder flow and tabletability were assessed on a small scale using ring shear tester and using a single punch compaction simulator, which can be easily integrated during the process of solid form screening activity for early preformulation studies. In addition, mechanical responses on single crystals were evaluated with nanoindentation. Indentation performed on three faces of piroxicam single crystals resulted reproducible results when compared with the literature, indicating the efficiency of this technique to perform single crystal characterization. The study highlights that, the early assessment of key material properties during solid form screening can aid in selecting optimal solid forms provided physicochemical properties are acceptable. (C) 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved