Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines—Pfizer and Moderna—that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends.
Bacterial spoilage of food products is regulated by density dependent communication system called quorum sensing (QS). QS control biofilm formation in numerous food pathogens and Biofilms formed on food surfaces act as carriers of bacterial contamination leading to spoilage of food and health hazards. Agents inhibiting or interfering with bacterial QS and biofilm are gaining importance as a novel class of next-generation food preservatives/packaging material. In the present study, Zinc nanostructures were synthesised using Nigella sativa seed extract (NS-ZnNPs). Synthesized nanostructures were characterized hexagonal wurtzite structure of size ~24 nm by UV-visible, XRD, FTIR and TEM. NS-ZnNPs demonstrated broad-spectrum QS inhibition in C. violaceum and P. aeruginosa biosensor strains. Synthesized nanostructures inhibited QS regulated functions of C. violaceum CVO26 (violacein) and elastase, protease, pyocyanin and alginate production in PAO1 significantly. NS-ZnNPs at sub-inhibitory concentrations inhibited the biofilm formation of four-food pathogens viz. C. violaceum 12472, PAO1, L. monocytogenes, E. coli. Moreover, NS-ZnNPs was found effective in inhibiting pre-formed mature biofilms of the four pathogens. Therefore, the broad-spectrum inhibition of QS and biofilm by biogenic Zinc oxide nanoparticles and it is envisaged that these nontoxic bioactive nanostructures can be used as food packaging material and/or as food preservative.
Sleep disturbances, as well as sleep-wake rhythm disturbances, are typical symptoms of Alzheimer's disease (AD) that may precede the other clinical signs of this neurodegenerative disease. Here, we describe clinical features of sleep disorders in AD and the relation between sleep disorders and both cognitive impairment and poor prognosis of the disease. There are difficulties of the diagnosis of sleep disorders based on sleep questionnaires, polysomnography or actigraphy in the AD patients. Typical disturbances of the neurophysiological sleep architecture in the course of the AD include deep sleep and paradoxical sleep deprivation. Among sleep disorders occurring in patients with AD, the most frequent disorders are sleep breathing disorders and restless legs syndrome. Sleep disorders may influence circadian fluctuations of the concentrations of amyloid-β in the interstitial brain fluid and in the cerebrovascular fluid related to the glymphatic brain system and production of the amyloid-β. There is accumulating evidence suggesting that disordered sleep contributes to cognitive decline and the development of AD pathology. In this mini-review, we highlight and discuss the association between sleep disorders and AD.
Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction. In clinical practice, the process of phenotyping of CYP isoenzymes and some endogenous substrates in the ratio of cortisol to 6β-hydroxycortisol in urine for the evaluation of CYP3A4 activity has been deemed to be a quite promising, safe and minimally invasive method for patients nowadays.
27 March 2017 in Current Topics in Medicinal Chemistry
The brain of patients with Alzheimer disease (AD) showed the evidence of reduced expression of insulin and neuronal insulin receptors, as compared with those of age-matched controls. This event gradually and certainly leads to a breakdown of the entire insulin-signaling pathway, which manifests insulin resistance. This in turn affects brain metabolism and cognitive functions, which are the bestdocumented abnormalities in AD. These observations led Dr. de la Monte and her colleagues to suggest that AD is actually a neuroendocrine disorder that resembles type 2 diabetes mellitus. The truth would be more complex with understanding the role of low-density lipoprotein receptor-related protein 1, Aβ derived diffusible ligands, and advanced glycation end products. However, now it known as “brain diabetes” and is called type 3 diabetes mellitus (T3DM). This review provides an overview of “brain diabetes” focusing on the reason why the phenomenon is called T3DM.