Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

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Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

Nanotechnology has begun to play a remarkable role in various fields of science and technology. In biomedical applications, nanoparticles have opened new horizons, especially for biosensing, targeted delivery of therapeutics, and so forth. Among drug delivery systems (DDSs), smart nanocarriers that respond to specific stimuli in their environment represent a growing field. Nanoplatforms that can be activated by an external application of light can be used for a wide variety of photoactivated therapies, especially light-triggered DDSs, relying on photoisomerization, photo-cross-linking/un-cross-linking, photoreduction, and so forth. In addition, light activation has potential in photodynamic therapy, photothermal therapy, radiotherapy, protected delivery of bioactive moieties, anticancer drug delivery systems, and theranostics (i.e., real-time monitoring and tracking combined with a therapeutic action to different diseases sites and organs). Combinations of these approaches can lead to enhanced and synergi...

Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light

Wastewater is a complex matrix containing a wide range of chemical and biological markers of human activity. Relating concentrations of these "waste" materials in wastewater influent streams to population-scale use, consumption, or rates of exposure, can provide important qualitative or quantitative information on the activity of inhabitants within a given wastewater catchment. Many publications in this field of study have focussed on the usage of pharmaceuticals, illicit drugs, tobacco and alcohol. However, many other potential applications are emerging which can contribute useful knowledge on human health, exposure to industrial chemicals, infectious diseases or pathogens and antibiotic resistance. This review summarises the established wastewater based epidemiology (WBE) biomarkers, and presents a critical review of the current capabilities of WBE. We further discuss possible future strategies and challenges anticipated in analysing wastewater to measure chemical markers of population health as well as biological markers of microbial exposure and disease. (c) 2018 Elsevier B.V. All rights reserved.

Wastewater-based epidemiology biomarkers: Past, present and future

Various drug delivery approaches can be used to maximize therapeutic efficacy and minimize side effects, by impacting absorption, distribution, metabolism, and elimination (ADME) of a drug compound. For those drugs with poor water solubility or low permeability, techniques such as amorphous solid dispersion, liposomes, and complexations have been used to improve their oral bioavailability. Modified release (MR) formulations have been widely used to improve patient compliance, as well as to reduce side effects, especially for those drugs with short half-lives or narrow therapeutic windows. More than ten drugs using sterile long-acting release (LAR) formulations with clear clinical benefit have been successfully marketed. Furthermore, drug delivery systems have been used in delaying drug clearance processes. Additionally, modifying the in vivo drug distribution using targeted delivery systems has significantly improved oncology treatments. All the drug delivery approaches have their advantages and limitations. For both brand and generic drugs, the achievement of consistent quality and therapeutic performance using drug delivery systems can also pose serious challenges in developing a drug for the market, which requires close collaboration among industry, academia, and regulatory agencies. With the advent of personalized medicines, there will be great opportunities and challenges in utilizing drug delivery systems to provide better products and services for patients.

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Drug Delivery Approaches in Addressing Clinical Pharmacology-Related Issues: Opportunities and Challenges

New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: "new psychoactive substances", "synthetic cathinones", "substituted cathinones", "mephedrone", "methylone", "MDPV", "4-MEC", "addiction", and "substance use disorder".

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Synthetic Cathinones: A New Public Health Problem

http://if-pan.krakow.pl/pjp/pdf/2013/1_1.pdf

Prodrugs: A challenge for the drug development

Designer cathinones--an emerging class of novel recreational drugs.

Smokeable herbal mixtures containing synthetic agonists of cannabinoid receptors, known under brand names such as Spice, K2 and Kronic, represent a relatively new type of designer psychoactive drugs that has recently emerged on the recreational drug market. Although the Spice packages are labelled 'not for human consumption' or 'for aromatherapy only' and declared to be purely herbal, these herbal mixtures produce cannabis-like effects after smoking. This review surveys the current state of knowledge regarding the pharmacological properties of synthetic cannabimimetics and the prevalence and pattern of their use. Special emphasis is given to the negative consequences of using these products, including, among others, hallucinations, psychoses with delusions, seizures, cardiovascular symptoms and acute kidney injury.

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Spice/K2 drugs--more than innocent substitutes for marijuana.

Recent years have witnessed a rapid increase in the number and prevalence of novel psychoactive substances (NPSs). Among them, pyrovalerone derivatives, including 3,4-methylenedioxypyrovalerone (3,4-MDPV), α-pyrrolidinopentiophenone (α-PVP), α-pyrrolidinobutiophenone (α-PBP), α-pyrrolidinopropiophenone (α-PPP), α-pyrrolidinohexanophenone (α-PHP), α-pyrrolidinoheptanophenone (α-PHPP), α-pyrrolidinooctanophenone (α-POP) and their substituted analogs, form a subgroup of designer cathinones endowed with highly pronounced psychostimulant effects, and these deserve special attention by healthcare specialists. This review focuses on recent members of this group, their in vitro and in vivo mechanisms of action and pharmacological activities, and their main metabolic pathways. The toxic properties of pyrovalerone derivatives are summarized, along with numerous case reports of fatal and non-fatal intoxications. Pyrovalerone derivatives are also associated with a growing number of reports of DUID (driving under the influence of drugs) and multidrug abuse, suggesting that they should be considered as posing a serious threat to public health.

α-Pyrrolidinophenones: a new wave of designer cathinones

The abuse of new psychoactive substances (NPS) has been increasing dramatically since the late 2000s worldwide. Between 2009 and 2017, a total of 803 individual NPS were reported to the United Nations Office of Drugs and Crime by 111 countries and territories. Although the most popular compounds are synthetic cannabinomimetics and psychostimulatory derivatives of cathinone (so-called β-keto-amphetamines), novel benzodiazepines have recently emerged on the recreational drug market. The misuse/abuse of "designer benzodiazepines" (DBZD), a common name for the benzodiazepine class NPS, has become an increasing problem in many countries. The DBZD group includes pharmaceutical drug candidates that have never been approved for medical use, compounds that were synthesized by a simple structural modification of a registered drug, and some active metabolites of registered benzodiazepines. This survey presents members of the DBZD group, describes the epidemiological trends and clinical effects associated with DBZD use, and discusses available data on their metabolism. Special emphasis is given to cases of intoxications involving these compounds.

Jakub Wojcieszak

Papers

Prodrugs: A challenge for the drug development

Designer cathinones--an emerging class of novel recreational drugs.

Spice/K2 drugs--more than innocent substitutes for marijuana.

α-Pyrrolidinophenones: a new wave of designer cathinones

An expanding world of new psychoactive substances-designer benzodiazepines.