Improving the safety efficacy ratio of existing drugs is a current challenge to be addressed rather than the development of novel drugs which involve much expense and time. The efficacy of drugs is affected by a number of factors such as their low aqueous solubility, unequal absorption along the gastrointestinal (GI) tract, risk of degradation in the acidic milieu of the stomach, low permeation of the drugs in the upper GI tract, systematic side effects, etc. This review aims to enlighten readers on the role of pH sensitive hydrogels in drug delivery, their mechanism of action, swelling, and drug release as a function of pH change along the GI tract. The basis for the selection of materials, their structural features, physical and chemical properties, the presence of ionic pendant groups, and the influence of their pKa and pKb values on the ionization, consequent swelling, and targeted drug release are also highlighted.
Microbes usually exist in communities consisting of myriad different but interacting species. These interactions are typically mediated through environmental modifications; microbes change the environment by taking up resources and excreting metabolites, which affects the growth of both themselves and also other microbes. We show here that the way microbes modify their environment and react to it sets the interactions within single-species populations and also between different species. A very common environmental modification is a change of the environmental pH. We find experimentally that these pH changes create feedback loops that can determine the fate of bacterial populations; they can either facilitate or inhibit growth, and in extreme cases will cause extinction of the bacterial population. Understanding how single species change the pH and react to these changes allowed us to estimate their pairwise interaction outcomes. Those interactions lead to a set of generic interaction motifs—bistability, successive growth, extended suicide, and stabilization—that may be independent of which environmental parameter is modified and thus may reoccur in different microbial systems.
The ocean’s chemistry is changing due to the uptake of anthropogenic carbon dioxide (CO2). This phenomenon, commonly referred to as “Ocean Acidification”, is endangering coral reefs and the broader marine ecosystems. In this study, we combine a recent observational seawater CO2 data product, i.e., the 6th version of the Surface Ocean CO2 Atlas (1991–2018, ~23 million observations), with temporal trends at individual locations of the global ocean from a robust Earth System Model to provide a high-resolution regionally varying view of global surface ocean pH and the Revelle Factor. The climatology extends from the pre-Industrial era (1750 C.E.) to the end of this century under historical atmospheric CO2 concentrations (pre-2005) and the Representative Concentrations Pathways (post-2005) of the Intergovernmental Panel on Climate Change (IPCC)’s 5th Assessment Report. By linking the modeled pH trends to the observed modern pH distribution, the climatology benefits from recent improvements in both model design and observational data coverage, and is likely to provide improved regional OA trajectories than the model output could alone, therefore, will help guide the regional OA adaptation strategies. We show that air-sea CO2 disequilibrium is the dominant mode of spatial variability for surface pH, and discuss why pH and calcium carbonate mineral saturation states, two important metrics for OA, show contrasting spatial variability.
Erez Persi, Miquel Duran-Frigola, Mehdi Damaghi
et al.
A reverse pH gradient is a hallmark of cancer metabolism, manifested by extracellular acidosis and intracellular alkalization. While consequences of extracellular acidosis are known, the roles of intracellular alkalization are incompletely understood. By reconstructing and integrating enzymatic pH-dependent activity profiles into cell-specific genome-scale metabolic models, we develop a computational methodology that explores how intracellular pH (pHi) can modulate metabolism. We show that in silico, alkaline pHi maximizes cancer cell proliferation coupled to increased glycolysis and adaptation to hypoxia (i.e., the Warburg effect), whereas acidic pHi disables these adaptations and compromises tumor cell growth. We then systematically identify metabolic targets (GAPDH and GPI) with predicted amplified anti-cancer effects at acidic pHi, forming a novel therapeutic strategy. Experimental testing of this strategy in breast cancer cells reveals that it is particularly effective against aggressive phenotypes. Hence, this study suggests essential roles of pHi in cancer metabolism and provides a conceptual and computational framework for exploring pHi roles in other biomedical domains. Tumors often exhibit a pH gradient, with an acidic extracellular space and alkaline cytoplasm. Here the authors develop a computational model to show how alkaline pHi supports changes inherent to cancer cell metabolism and acidification disables these adaptations, and demonstrate the effect of acidic pHi on breast cancer cell survival.
L. Palanikumar, Sumaya Al-Hosani, M. Kalmouni
et al.
The practical application of nanoparticles (NPs) as chemotherapeutic drug delivery systems is often hampered by issues such as poor circulation stability and targeting inefficiency. Here, we have utilized a simple approach to prepare biocompatible and biodegradable pH-responsive hybrid NPs that overcome these issues. The NPs consist of a drug-loaded polylactic-co-glycolic acid (PLGA) core covalently ‘wrapped’ with a crosslinked bovine serum albumin (BSA) shell designed to minimize interactions with serum proteins and macrophages that inhibit target recognition. The shell is functionalized with the acidity-triggered rational membrane (ATRAM) peptide to facilitate internalization specifically into cancer cells within the acidic tumor microenvironment. Following uptake, the unique intracellular conditions of cancer cells degrade the NPs, thereby releasing the chemotherapeutic cargo. The drug-loaded NPs showed potent anticancer activity in vitro and in vivo while exhibiting no toxicity to healthy tissue. Our results demonstrate that the ATRAM-BSA-PLGA NPs are a promising targeted cancer drug delivery platform. Palanikumar et al. prepare pH-responsive nanoparticles with drug-loaded PLGA core, cross-linked BSA corona to avoid opsonisation, and functionalised with ATRAM peptide that binds the cell membrane at low pH such as tumour microenvironment. The nanoparticles display both in vitro and in vivo efficacy while evading recognition by macrophages.
Microbes from the three domains of life, Bacteria, Archaea, and Eukarya, share the need to sense and respond to changes in the external and internal concentrations of protons. When the proton concentration is high, acidic conditions prevail and cells must respond appropriately to ensure that macromolecules and metabolic processes are sufficiently protected to sustain life. While, we have learned much in recent decades about the mechanisms that microbes use to cope with acid, including the unique challenges presented by organic acids, there is still much to be gained from developing a deeper understanding of the effects and responses to acid in microbes. In this perspective article, we survey the key molecular mechanisms known to be important for microbial survival during acid stress and discuss how this knowledge might be relevant to microbe-based applications and processes that are consequential for humans. We discuss the research approaches that have been taken to investigate the problem and highlight promising new avenues. We discuss the influence of acid on pathogens during the course of infections and highlight the potential of using organic acids in treatments for some types of infection. We explore the influence of acid stress on photosynthetic microbes, and on biotechnological and industrial processes, including those needed to produce organic acids. We highlight the importance of understanding acid stress in controlling spoilage and pathogenic microbes in the food chain. Finally, we invite colleagues with an interest in microbial responses to low pH to participate in the EU-funded COST Action network called EuroMicropH and contribute to a comprehensive database of literature on this topic that we are making publicly available.
Widespread usage of silver nanoparticles (AgNPs) in consumer products has resulted in their presence in the aquatic environment. The evolution of the properties of AgNPs with changes in pH and time in terms of colloidal stability, dissolution and aggregation were investigated in a series of short and long-term experiments using freshly synthesized uncoated AgNPs. The solution pH modifies the surface charge and the oxidative dissolution of AgNPs. As a result, the particle behavior varied in acidic and alkaline conditions. The particle size decreased with the increasing pH at a given time frame resulting in lower aggregation in the higher pH regime and increased particle stability. These results have been further proved with the direct evidence obtained using time resolved in situ imaging acquired through Liquid cell transmission electron microscopy (LCTEM). Furthermore, the magnitude of the impact of the pH on the particle properties is higher than the impact of the dissolved oxygen concentration. The derived empirical formulae reflect that the AgNP oxidation depends on both dissolved oxygen and protons while the AgNP dissolution increasing with the increase of either of these. Overall, our results highlight the impact of the solution pH on the evolution of the properties of AgNPs over the time and provide an insight to confidently extend the results to predict the environmental transformation of AgNPs from ideal systems to the real.
pH-sensing materials and configurations are rapidly evolving toward exciting new applications, especially those in biomedical applications. In this review, we highlight rapid progress in electrochemical pH sensors over the past decade (2008-2018) with an emphasis on key considerations, such as materials selection, system configurations, and testing protocols. In addition to recent progress in optical pH sensors, our main focus in this review is on electromechanical pH sensors due to their significant advances, especially in biomedical applications. We summarize developments of electrochemical pH sensors that by virtue of their optimized material chemistries (from metal oxides to polymers) and geometrical features (from thin films to quantum dots) enable their adoption in biomedical applications. We further present an overview of necessary sensing standards and protocols. Standards ensure the establishment of consistent protocols, facilitating collective understanding of results and building on the current state. Furthermore, they enable objective benchmarking of various pH-sensing reports, materials, and systems, which is critical for the overall progression and development of the field. Additionally, we list critical issues in recent literary reporting and suggest various methods for objective benchmarking. pH regulation in the human body and state-of-the-art pH sensors (from ex vivo to in vivo) are compared for suitability in biomedical applications. We conclude our review by (i) identifying challenges that need to be overcome in electrochemical pH sensing and (ii) providing an outlook on future research along with insights, in which the integration of various pH sensors with advanced electronics can provide a new platform for the development of novel technologies for disease diagnostics and prevention.
Abstract Hydroxyl radicals (·OH) are most important reactive oxygen species (ROSs) for organic pollution controlling in advanced oxidation processes, while its production suffers from numerous H2O2 addition and narrow pH range in generally used Fenton reaction. Herein, we demonstrate a BiOIO3 (BIO) piezo-catalyst loaded with γ-FeOOH quantum dots (FQDs) (BF) that can convert O2 to ·OH in a wide pH condition without external H2O2 addition under ultrasonication. It is found that the robust interfacial interaction facilitates rapid electron migration from BIO to FQDs, enabling two-electron O2 reduction into H2O2 at the FQDs site, while the leaving behind piezo-holes perform two-electron water oxidative H2O2 generation on BIO. Because the electron-rich nature of FQDs favors the H⁺ adsorption that contributes a surface acidic micro-environment, the produced H2O2 can be in-situ catalyzed into ·OH in either neutral or even alkaline conditions with a great stability. Finally, the optimal BF can achieve either an impressive ·OH yield of 38.1 µM h− 1 or an exceptional H2O2 yield of 522.0 µM h− 1 by regulating the FQDs loading mass, which enables a dual capabilities of rapid organic pollutants degradation and H2O2 production in a wide pH condition.
A synthesis of long-term changes in pH of coastal ecosystems shows that, in contrast to the uniform trends of open-ocean acidification (-0.0004 to -0.0026 pH units yr-1) driven by increased atmospheric CO2, coastal ecosystems display a much broader range of trends (-0.023 to 0.023 pH units yr-1) and are as likely to show long-term increase as decline in pH. The majority of the 83 investigated coastal ecosystems displayed nonlinear trends, with seasonal and interannual variations exceeding 1 pH unit for some sites. The high pH variability of coastal ecosystems is primarily driven by inputs from land. These include freshwater inputs that typically dilute the alkalinity of seawater thereby resulting in reduced buffering, nutrients enhancing productivity and pH, as well as organic matter supporting excess respiration driving acidification. For some coastal ecosystems, upwelling of nutrient-rich and corrosive water may also contribute to variability in pH. Metabolic control of pH was the main factor governing variability for the majority of coastal sites, displaying larger variations in coastal ecosystems with low alkalinity buffering. pH variability was particularly pronounced in coastal ecosystems with strong decoupling of production and respiration processes, seasonally or through stratification. Our analysis demonstrate that coastal pH can be managed by controlling inputs of nutrients, organic matter, and alkalinity. In well-mixed coastal waters, increasing productivity can improve resistance to ocean acidification, whereas increasing productivity enhances acidification in bottom waters of stratified coastal ecosystems. Environmental management should consider the balance between the negative consequences of eutrophication versus those of acidification, to maintain biodiversity and ecosystem services of our coastal ecosystems.
Abstract Localized pH measurements are important in various areas of electrochemistry, from corrosion to bio-electrochemistry and electrocatalysis. Different techniques are available to perform these measurements and offer numerous possibilities in terms of spatial and temporal resolution, sensitivity, and precision. In this brief review we present the recent progress made and summarize the main techniques available for localized pH measurements in electrochemistry such as scanning probe techniques (SECM, SICM, SIET), laser (confocal) fluorescence microscopy, rotating ring-disc electrode (RRDE) voltammetry, and infra-red spectroscopy, among others.
Leandra de Carvalho Lacerda, Alexandre Swarowsky, Janine Farias Menegaes
et al.
As áreas agrícolas vêm sendo constantemente contaminadas pelo excesso de aplicações de produtos agrícolas, entre eles o cobre (Cu), nas áreas vitivinícolas. Assim, buscando uma agricultura de baixo impacto ambiental, o objetivo deste trabalho foi avaliar o desenvolvimento vegetativo de tagetes (Tagetes patula L.) em resposta ao excesso de Cu em diferentes pH no solo. O experimento ocorreu na casa de vegetação utilizando delineamento inteiramente casualizado, com fatorial 5x2 (doses adicionadas de Cu no solo: 0 (sem adição: testemunha), 250, 500, 750 e 1.000 mg kg-1 de Cu e correções de pH no solo: 5,5 e 6,0 de acordo com o laudo da análise do solo), com cinco repetições. Avaliaram-se parâmetros fitotécnicos conteúdos de nutrientes na massa seca, fatores fitorremediativos e taxa de extração de Cu na planta. Verificou-se que as plantas de tagetes apresentaram bom crescimento e desenvolvimento vegetativo em ambos os pH no solo, todavia, o incremento de Cu no solo afetou negativamente a altura de planta. Não houve indícios de fitotoxidez das plantas, assim concluiu-se que as plantas de tagetes são tolerantes em áreas contendo altas concentrações de Cu no solo, sem alterar suas características ornamentais.
Abderrahman Rachidi, Tarek El Bardouni, Otman El Hajjaji
$^{7}Be$ an isotope emanating from cosmogenic origins due to high energy cosmic rays, is studied from its production to its detection in the surface, in order to elucidate atmospheric circulation phenomena and analyze the vertical transport of air masses. This can be illustrated briefly by the monsoon model in Kerala in India, where the application of the $^{7}Be$ detection methods in stations in Russia and Australia offered predictions of the debut and retreat of moonsoon saison in contrast to the meteorological methods.