Gelatin and bovine serum albumin (BSA), two readily available biopolymers, were examined for their effect on solubility and supersaturation of drugs because of their capacity to interact with drugs (e.g. via hydrogen bonding, van der Waals or electrostatic interactions, etc.). Carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen were selected accordingly as twelve structurally different model BCS Class II drugs. All selected drugs were evaluated for solubility and supersaturation in presence and absence of these two biopolymers in four media (purified water, FaSSIF, FaSSGF and FeSSIF) by means of the shake flask method for 48h and solvent shift induced supersaturation, respectively. In ca. 75% of the supersaturation experiments with these two biopolymers, drug concentrations significantly different (p > 0.05) from solubility were observed with supersaturation factors (SF) varying between 1.28 and 7.89 (p ≤ 0.05) and between 1.16 and 20.51 (p ≤ 0.01). In order to make an estimation on the relevance of these results, a comparison with three commonly used (semi-) synthetic polymers (HPMC, PVP and PVPVA) was included in purified water. This showed that both biopolymers were at least as efficient as the (semi-) synthetic polymers in sustaining induced supersaturation as in ten out of twelve API comparable results were obtained.

Phospholipase A2 (PLA2 ) is one of the rate limiting enzymes involved in the production of arachidonic acid, a potent inflammatory mediator. PLA2 is widely distributed all over the animal kingdom. It is also seen in inflammatory exudation and venoms of different organisms. The studies demonstrated that PLA2 inhibitors have broad spectrum activities that they can either be used against inflammation or envenomation. In this study, the inhibitory activity of 1-napthaleneacetic acid (NAA) against porcine pancreatic PLA2 has been explained through isothermal titration calorimetry and enzyme kinetics studies. The atomic level of interactions of NAA with PLA2 was also studied using X-ray crystallography. Apart from these findings, the theoretical binding affinities and mode of interactions of two naphthalene-based NSAIDs such as naproxen (NAP) and nabumetone (NAB) were studied through molecular modeling. The studies proved that the selected ligands are binding at the doorway of the active site cleft and hindering the substrate entry to the active site. The study brings out a potential scaffold for the designing of broad spectrum PLA2 inhibitors which can be used for inflammation or envenomation. © 2018 IUBMB Life, 9999(9999):1-7, 2018.

A passive sampling device, a polar organic chemical integrative sampler (POCIS), was used to monitor 13 pharmaceuticals and 8 transformation products in upstream and downstream wastewater treatment plant effluent. A POCIS laboratory calibration study was performed to determine uptake behavior and the effect of water flow on the sampling rate. Most compounds showed a linear accumulation, and the sampling rate values ranged from 0.031 to 0.559 L/day. The developed POCIS samplers were used in field experiments in a wastewater-impacted river. Using the calculated sampling rates, the time-weighted average concentration values were measured by three different approaches: (1) laboratory calibration sampling rates (2) performance reference compound (PRC) correction sampling rates and (3) field calibration sampling rates. Nine deuterated compounds (acetaminophen-d3, antipyrine-d3, sulfamethoxazole-d4, carbamazepine-d10, diclofenac acid-d4, clofibric acid-d4, bezafibrate-d6, ibuprofen-d3 and naproxen-d3) were studied as PRCs. Antipyrine-d3 was successfully tested as a PRC for sulfamethoxazole, ibuprofen, 2-hydroxy ibuprofen, diclofenac acid, 4-hydroxydiclofenac acid, carbamazepin, carbamazepin 10,11-epoxide, sulfadiazine, 1-naphthol, antipyrine, naproxen and 4-chlorobenzoic acid. Finally, the POCIS was used to monitor target compounds in river water and measure their attenuation. For most compounds, the POCIS attenuation results were not significantly different from those of the spot samples, which demonstrated that a POCIS with a PRC correction can determine the attenuation of organic micropollutants in rivers.

The by-products produced by pharmaceutically active compounds (PhACs) during chlorination are attracting wide concern. Thus, the transformation and toxicity of naproxen (NAP) during the chlorination process were assessed in this study. The transformation of NAP was found to follow pseudo-first-order kinetics, and the first-order rate constant was improved by increasing the NaOCl dose. High-resolution mass spectrometry (HRMS) was successfully applied to identify 14 chlorination products. This study represents the first elucidation and report of the exact structure of the primary chlorine substitution product ((2S)-2-(5-chloro-6-methoxy-2-naphthyl)propionic acid) based on HRMS and 1H NMR. Chlorine will primarily substitute the hydrogen atom on the C7 position of the naphthalene ring to form the mono-chlorine substitution product, as further validated at the theoretical level by quantum chemical calculations. A series of HOCl-induced reactions, including substitution, demethylation, and dehydrogenation, led to the transformation of NAP during the chlorination process. ECOSAR program revealed that the potential aquatic toxicity of the transformation products is significantly higher than that of the parent NAP. Their introduction into the environment may still pose potential risks.

In order to obtain a non-toxic amphiphilic calixresorcinarene capable to form nanoconjugates for drug encapsulation, tetraundecylcalixresorcinarene functionalized by methoxy poly(ethylene glycol) chains has been synthesized. The macrocycle obtained is characterized by low hemotoxicity. In aqueous solution it forms nanoassociates that are able to encapsulate organic substrates of different hydrophobicity, including drugs (doxorubicin, naproxen, ibuprofen, quercetin). The micelles of the macrocycle slowed down the release of the hydrophilic substrates in vitro. In physiological sodium chloride solution and phosphate-buffered saline, the micelles of the macrocycle acquire thermoresponsive properties and exhibit a temperature-controlled release of doxorubicin in vitro. The combination of the low toxicity and the encapsulation properties of the obtained calixresorcinarene-mPEG conjugate shows promising potential for the use as a supramolecular drug-delivery system.

Small molecule-based amphiphiles self-assemble into nanostructures (micelles) in aqueous medium which are currently being explored as novel drug delivery systems. Here, naproxen-polyethylene glycol (N-PEG), a small molecule-derived amphiphile, has been synthesised, characterised and evaluated as hydrophobic drug carrier. 1H, 13C Nuclear magnetic resonance (NMR), mass spectrometry (MS) and Fourier-transform infrared spectroscopy (FTIR) confirmed the formation of N-PEG and dynamic light scattering (DLS) revealed the formation of nano-sized structures of ∼228 nm. Transmission electron microscope (TEM) analysis showed aggregation behaviour of the structures with average size of ∼230 nm. Biodegradability aspect of the micellar-structured N-PEG was demonstrated by lipase-mediated degradation studies using DLS and TEM. High encapsulation efficiency followed by release in a sustained manner of a well-known anticancer drug, doxorubicin, demonstrated the feasibility of the new drug delivery system. These results advocate the promising potential of N-PEG micelles as efficient drug delivery system for specific delivery to cancerous cells in vitro and in vivo.

Substantial efforts are underway for prevention of early stages or recurrence of colorectal cancers (CRC) or new polyp formation by chemoprevention strategies. Several epidemiological, clinical and preclinical studies to date have supported the chemopreventive potentials of several targeted drug classes including non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin, naproxen, sulindac, celecoxib, and licofelone), statins and other natural agents-both individually, and in combinations. Most preclinical trials although were efficacious, only few agents entered clinical trials and have been proven to be potential chemopreventive agents for colon cancer. However, there are limitations for these agents that hinder their approval by the food and drug administration for chemoprevention use in high-risk individuals and in patients with early stages of CRC. In this review, we update the recent advancement in pre-clinical and clinical development of selected anti-inflammatory agents (aspirin, naproxen, sulindac, celecoxib, and licofelone) and their combinations for further development as novel colon cancer chemopreventive drugs. We provide further new perspectives from this old research, and insights into precision medicine strategies to overcome unwanted side-effects and overcoming strategies for colon cancer chemoprevention.

Nonsteroidal anti-inflammatory pharmaceuticals are emerging organic micropollutants in surface water, groundwater, and wastewater, whose removal is very important yet challenging. As a new class of porous functional materials, metal-organic frameworks (MOFs) have attracted extensive attention for their adsorption applications. Here, we report that Zr(IV)-based MOFs (defective UiO-66, and MOF-808) have extraordinary adsorption ability to remove nonsteroidal anti-inflammatory pharmaceuticals from water. Excellent adsorption performances are obtained for UiO-66 and MOF-808, particularly for UiO-66, of which the adsorption capacities are the highest in a wide series of adsorptive materials previously reported. It is elucidated that the incomplete-coordinated cationic Zr in the cluster has high affinity for the anionic pharmaceutical (chemical adsorption) and that the adsorption interaction between the benzene ring of the pharmaceutical and MOF's ligand is involved to enhance or as an alternative to the adsorption interactions (π-π interaction). In particular, adsorption of ibuprofen, ketoprofen, naproxen, indomethacin, and furosemide by UiO-66 and MOF-808 and the synergetic effect of chemical adsorption and π-π interaction are outstanding, leading to extremely higher binding energies ( Ebind) and sorption abilities.

Electrospinning process of nanofibers specially derivatives of cellulose presents high behest for developing several kinds of novel drug delivery systems (DDSs) due to their specific characteristics, the simplicity, beneficial and impressive top-down fabricating procedure. Moreover, the novel techniques of therapeutic agents for entrapment into core-shell nanofibers including single, coaxial and triaxial applied for DDSs. Recently, biodegradable polymers including derivatives of cellulose, hybrid materials, artificial and natural polymers have been remarkably considered. The acetate ester of cellulose (cellulose acetate (CA)), has been widely used due to biodegradability, chemical persistence, biocompatibility, and thermal constancy for DDSs. This article submits an overview of CA electrospinning techniques, applications, and its usage as a carrier for therapeutic agents in DDSs. Furthermore, in this study, we aimed to summarize the classification of therapeutic agents comprising antimicrobial agents incorporated CA fibers, antibacterial nanoparticles incorporated CA fibers, antioxidant agents loaded CA nanofibers, systematic and anti-inflammatory agents containing CA nanofibers. Our study has been concluded that CA electrospun nanofibers could be potentially applied as biocompatible and biodegradable for DDSs specifically in purpose-designed transdermal or wound dressing patches.