Cocrystallizing and Codelivering Complementary Drugs to MultidrugResistant Tuberculosis Bacteria in Perfecting Multidrug Therapy.

Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria.

Soot-Based Reduced Graphene Quantum Dot/Hemin Conjugate for Favipiravir Sensing

A conjugated system was synthesized from reduced graphene quantum dot (rGQD) and hemin for the selective detection of favipiravir (Fav), an antiviral drug that has come into much attention during the year 2020 for its use as a drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The required rGQD was prepared from soot particles using Hummers' method followed by the amino-hydrothermal process. At the first step, its fluorescence was quenched by preparing the conjugate with hemin. Interestingly, the fluorescence intensity gradually increases (turn-on) with increasing concentration of Fav, and develops 9-fold higher fluorescence at 15.6 nM of Fav. The fluorescence enhancement is selective, and the limit of detection (LOD) was calculated to be about 1.96 nM. The fluorescence turn-on is governed by aggregation-induced emission (AIE), which originates from electrostatic interactions between the sensor-analyte systems. A similar fluorescence turn-on was observed for Fav in human blood plasma (BP) as well as in artificial urine (AU), which indicates that the sensor is viable in real-sample analysis. In addition to Fav, its 1:1 cocrystals with theophylline (Theo) and ferulic acid (FRA) also enhance the fluorescence in real samples with an LOD of 3.47 and 12.2 nM, respectively. Therefore, the cocrystals remain intact in biological medium and the sensor interacts with cocrystals too. The detection of Fav and its cocrystals, and the development of cocrystals as alternatives in the pharmaceutical industry, is essential considering the current COVID-19 pandemic worldwide. Therefore, the findings of this work will certainly help in developing fluorescence sensors for quantitative determination of active pharmaceutical ingredients (APIs) in real samples. © 2021 American Chemical Society.

Are Myths and Preconceptions Preventing us from Applying Ionic Liquid Forms of Antiviral Medicines to the Current Health Crisis?

At the moment, there are no U.S. Food and Drug Administration (U.S. FDA)-approved drugs for the treatment of COVID-19, although several antiviral drugs are available for repurposing. Many of these drugs suffer from polymorphic transformations with changes in the drug's safety and efficacy; many are poorly soluble, poorly bioavailable drugs. Current tools to reformulate antiviral APIs into safer and more bioavailable forms include pharmaceutical salts and cocrystals, even though it is difficult to classify solid forms into these regulatory-wise mutually exclusive categories. Pure liquid salt forms of APIs, ionic liquids that incorporate APIs into their structures (API-ILs) present all the advantages that salt forms provide from a pharmaceutical standpoint, without being subject to solid-state matter problems. In this perspective article, the myths and the most voiced concerns holding back implementation of API-ILs are examined, and two case studies of API-ILs antivirals (the amphoteric acyclovir and GSK2838232) are presented in detail, with a focus on drug property improvement. We advocate that the industry should consider the advantages of API-ILs which could be the genesis of disruptive innovation and believe that in order for the industry to grow and develop, the industry should be comfortable with a certain element of risk because progress often only comes from trying something different.