Specific pH Research Articles

Formation, structure, properties of chitosan aspartate and metastable state of its solutions for obtaining nanoparticles

Chitosan (200 kDa) dissolution in an aqueous solution of L-aspartic acid, physicochemical properties and features of the resulting chitosan salt were studied by conductometry, potentiometry, viscometry, turbidimetry, IR and NMR spectroscopy, and X-ray diffractometry. Chitosan aspartate is a water-soluble hydrated polymorph exhibiting properties of a cationic polyelectrolyte with an effective macromolecular coil radius 60–75 nm. The specific conductivity, dielectric constant, viscosity and pH of the chitosan – L-aspartic acid – water system change over time after preparation due to counterion-polycation association to form ion pairs, multiplet structures, and their subsequent aggregation. As a result, nanoparticles (40–90 nm) are formed after ~24 h, microparticles (0.6–1.4 μm) are after ~48 h, and precipitation occurs after 72–96 h. The precipitated phase is a water-insoluble chitosan salt with a developed system of H-bonds and high crystallinity degree. Chitosan nanoparticles have high biocompatibility and the ability to accelerate the proliferative activity of epithelial cells. HypothesisIon pairs and multiplets are formed in the chitosan – L-aspartic acid – water system due to counterion association, which leads to phase segregation of the polymer substance at the level of nanoparticles and microparticles.

The influence of environmental parameters on the phytoplankton community of two tropical reservoirs

AbstractPrevious studies have indicated certain environmental variables such as rainfall, nutrient concentrations and mixing events can be strong drivers of the phytoplankton community structure in reservoirs. Shifts in the phytoplankton community composition of Puerto Rican reservoirs, however, are not well understood. The present study identified the spatial and temporal changes in the phytoplankton community structure of two reservoirs in Puerto Rica, and which environmental parameters determined the structure. Whether or not the main environmental variables varied on the basis of the initial trophic status of the reservoirs was also explored. Two Puerto Rican reservoirs, one classified as mesotrophic and the other as eutrophic, were sampled on three sampling dates, with the reservoirs into three zones (dam; transition; riverine). Physical parameters were recorded at each sampling site, nutrient concentrations were measured, and the phytoplankton community biomass and diversity were determined. A canonical correspondence analysis (CCA) was run for each reservoir to explore which variables determined the phytoplankton community composition. Temperature, pH and total phosphorus concentration were the main drivers of the phytoplankton community composition for the mesotrophic reservoir, while specific conductance, pH, total phosphorus and nitrate were the main explanatory variables. Although the driving variables changed between the reservoirs, the temporal shifts observed in the phytoplankton community structure were consistent for both reservoirs regardless of their trophic status. The findings of the present study suggest that, although shifts in the phytoplankton community structure are similar in reservoirs with differing initial trophic status, the environmental variables driving community composition may nevertheless vary. Accordingly, tropical reservoirs managers should consider a reservoir's initial trophic status when evaluating what environmental parameters may lead to changes in its phytoplankton community structure. The present study represents a first step at examining the variables driving phytoplankton community structure in Puerto Rican reservoirs.

Exploring uncertainty in thermodynamic modeling of the lead carbonate aqueous system

Abstract Thermodynamic models of the lead carbonate aqueous system have been used in prior studies to evaluate the effect of water chemistry on lead solubility and corrosion scale composition in water distribution systems. A common challenge in these studies is uncertainty arising from the thermodynamic equilibrium constants (logK values) used to parameterize the models. The objective of this study is to evaluate the way in which uncertainty in logK values propagates through thermodynamic models of the lead carbonate system and provide guidance for future modeling efforts. This was done by conducting a full factorial statistical analysis implemented using a custom Python (v3) code coupled with a PHREEQC (v1.4.2) geochemical model, along with batch lead solubility experiments. Two lead carbonate solid phases (cerussite and hydrocerussite) and nine aqueous lead complexes are considered in the geochemical model with conditions simulated ranging from pH 4 to 11 and dissolved inorganic carbon (DIC) ranging from 0 to 250 mg C/L. Main effect analysis indicates that model uncertainty is predominately associated with logK values for five species (in order of decreasing effect): hydrocerussite, , cerussite, PbOH+, and PbCO3o, with model uncertainty varying depending on the specific pH and DIC conditions simulated. Interaction effects show that logK values cannot be selected independently, as their influence on lead solubility is connected. Finally, by considering uncertainty in logK values it was possible for the thermodynamic model to match batch hydrocerussite solubility experimental data over a range of pH and DIC conditions. Six combinations of logK values that provided a good match between the simulated and experimental data were determined with the average difference between the simulated and experimental lead concentrations calculated to be 0.031 mg/L when the recommended logK value combination was used.

The Bioinorganic Chemistry of Mammalian Metallothioneins.

The functions, purposes, and roles of metallothioneins have been the subject of speculations since the discovery of the protein over 60 years ago. This article guides through the history of investigations and resolves multiple contentions by providing new interpretations of the structure-stability-function relationship. It challenges the dogma that the biologically relevant structure of the mammalian proteins is only the one determined by X-ray diffraction and NMR spectroscopy. The terms metallothionein and thionein are ambiguous and insufficient to understand biological function. The proteins need to be seen in their biological context, which limits and defines the chemistry possible. They exist in multiple forms with different degrees of metalation and types of metal ions. The homoleptic thiolate coordination of mammalian metallothioneins is important for their molecular mechanism. It endows the proteins with redox activity and a specific pH dependence of their metal affinities. The proteins, therefore, also exist in different redox states of the sulfur donor ligands. Their coordination dynamics allows a vast conformational landscape for interactions with other proteins and ligands. Many fundamental signal transduction pathways regulate the expression of the dozen of human metallothionein genes. Recent advances in understanding the control of cellular zinc and copper homeostasis are the foundation for suggesting that mammalian metallothioneins provide a highly dynamic, regulated, and uniquely biological metal buffer to control the availability, fluctuations, and signaling transients of the most competitive Zn(II) and Cu(I) ions in cellular space and time.

Covid-19 morbidity and outcomes among the patients observed in the pulmonary hypertension reference center

Abstract Background Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive condition with high mortality rate despite modern pharmacotherapy. There is no reliable data concerning influence of Covid-19 infection on PAH and CTEPH morbidity and mortality. Aim To evaluate influence 12-month Covid-19 pandemic presence on morbidity and mortality in patients with PAH and CTEPH observed in PH reference center. Methods During the 12 months (from March 2020 to March 2021) we closely follow-up the condition of 404 initially alive patients with on PAH and CTEPH with specific PH therapy who were observed in our reference center for adults. All information was checked and confirmed with proper medical documents and Covid-19 diagnosis was confirmed with positive PCR or/and serological tests. We finished our database with the vaccination beginning. Results Main data are presented in table. Among 404 patients symptomatic Covid-19 infection was documented in 44 (10,9%) cases. Only 9 (20,5%) of them were hospitalized because this reason, 4 patients of them (9,1% from all Covid-19 diagnosis and 44,4% from hospitalized) needed ICU because severe circulatory and respiratory failure. All of them needed the ventilator support. Unfortunately, despite of the necessary measures all of the ICU admitted patients died shortly during couple of days (mean 2,5±1,8). There was no difference in demographic, diagnosis and initial condition between hospitalized and ambulatory treated patients. The small numbers of died patients did not allow to make any statistically significant assumption. Conclusion During 12-months Covid-19 pandemic presence 11% of PAH and CTEPH patients had symptomatic COVID-19 infection, roughly 20% of them needed hospital admission and 10% needed ICU and ventilator support. The mortality in ICU was 100%. Funding Acknowledgement Type of funding sources: None. Table 1. Covid-19 morbidity and mortality among PAH and CTEPH patients

Multicolor PEGDA/LCNF Hydrogel in the Presence of Red Cabbage Anthocyanin Extract.

Colorimetric indicator gels were developed by incorporating anthocyanin (AC) obtained from red cabbage into poly (ethylene glycol) diacrylate (PEGDA)-based hydrogel containing lignocellulose nanofiber (LCNF). The PEGDA-based hydrogel was prepared by mixing all of the mentioned components at the specific composition, and the hydrogels were cured under UV light (245 nm) for 1 min. The pH-response, UV absorption, swelling ratio, and mechanical properties of PEGDA/LCNF were determined. It was further found that PEGDA and LCNF mount play an important role in adjusting the mechanical properties of PEGDA/LCNF. In general, the presence of LCNF improved the mechanical properties and swelling ratio of PEGDA. The incorporation of red cabbage anthocyanin into the PEGDA/LCNF film showed multicolor response when specific pH buffers were introduced. Based on the multicolor response of PEGDA/LCNF/CA, this gel film indicator can be developed as a food freshness indicator that focuses on the detection of ammonia and amine compound.

Comprehensive Insight into Chemical Stability of Important Antidiabetic Drug Vildagliptin Using Chromatography (LC-UV and UHPLC-DAD-MS) and Spectroscopy (Mid-IR and NIR with PCA).

During forced degradation, the intrinsic stability of active pharmaceutical ingredients (APIs) could be determined and possible impurities that would occur during the shelf life of the drug substance or the drug product could be estimated. Vildagliptin belongs to relatively new oral antidiabetic drugs named gliptins, inhibiting dipeptidyl peptidase 4 (DPP-4) and prolonging the activities of the endogenous incretin hormones. At the same time, some gliptins were shown as prone to degradation under specific pH and temperature conditions, as well as in the presence of some reactive excipients. Thus, forced degradation of vildagliptin was performed at high temperature in extreme pH and oxidative conditions. Then, selective LC-UV was used for quantitative determination of non-degraded vildagliptin in the presence of its degradation products and for degradation kinetics. Finally, identification of degradation products of vildagliptin was performed using an UHPLC-DAD-MS with positive ESI. Stability of vildagliptin was also examined in the presence of pharmaceutical excipients, using mid-IR and NIR with principal component analysis (PCA). At 70 °C almost complete disintegration of vildagliptin occurred in acidic, basic, and oxidative media. What is more, high degradation of vildagliptin following the pseudo first-order kinetics was observed at room temperature with calculated k values 4.76 × 10−4 s−1, 3.11 × 10−4 s−1, and 1.73 × 10−4 s−1 for oxidative, basic and acidic conditions, respectively. Next, new degradation products of vildagliptin were detected using UHPLC-DAD-MS and their molecular structures were proposed. Three degradants were formed under basic and acidic conditions, and were identified as [(3-hydroxytricyclo- [3.3.1.13,7]decan-1-yl)amino]acetic acid, 1-{[(3-hydroxytricyclo[3.3.1.13,7]decan-1-yl)amino]acetyl}-pyrrolidine-2-carboxylic acid and its O-methyl ester. The fourth degradant was formed in basic, acidic, and oxidative conditions, and was identified as 1-{[(3-hydroxytricyclo[3.3.1.13,7]-decan-1-yl)amino]acetyl}pyrrolidine-2-carboxamide. When stability of vildagliptin was examined in the presence of four excipients under high temperature and humidity, a visible impact of lactose, mannitol, magnesium stearate, and polyvinylpirrolidone was observed, affecting-NH- and CO groups of the drug. The obtained results (kinetic parameters, interactions with excipients) may serve pharmaceutical industry to prevent chemical changes in final pharmaceutical products containing vildagliptin. Other results (e.g., identification of new degradation products) may serve as a starting point for qualifying new degradants of vildagliptin as it is related to substances in pharmacopoeias.

Control and Preparation of Quaternized Chitosan and Carboxymethyl Chitosan Nanoscale Polyelectrolyte Complexes Based on Reactive Flash Nanoprecipitation.

Nanoscale polyelectrolyte complex materials have been extensively investigated for their promising application in protocell, drug carriers, imaging, and catalysis. However, the conventional preparation approach involving positive and negative polyelectrolytes leads to large size, wide size distribution, instability, and aggregation due to the nonhomogeneous mixing process. Herein, we employ reactive flash nanoprecipitation (RFNP) to control the mixing and preparation of the nanoscale polyelectrolyte complex. With RFNP, homogeneous mixing complexation between oppositely charged chitosan derivatives could be achieved, resulting in stable nanoscale complexes (NCs) with controllable size and narrow size distribution. The smallest size of NCs is found at specific pH due to the maximum attraction of positive and negative molecules of chitosan. The size can be modulated by altering the volumetric flow rates of inlet streams, concentration, and charge molar ratio of two oppositely charged chitosan derivatives. The charge molar ratio is also tuned to create NCs with positive and negative shells. There is no significant variation in the size of NCs produced at different intervals of time. This method allows continuous and tunable NC production and could have the potential for fast, practical translation.

Microfluidic Preparation of Janus Microparticles With Temperature and pH Triggered Degradation Properties.

Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.

Adsorption of antiretroviral drugs, efavirenz and nevirapine from aqueous solution by graphene wool: Kinetic, equilibrium, thermodynamic and computational studies

The increasing concentrations of pharmaceutical and personal care products in water bodies have attracted attention due to the risk of non-target exposures. The application of any graphene-based material for the remediation of antiretroviral drug contamination has not been reported, therefore graphene wool was synthesized by chemical vapour deposition as adsorbent for the removal of efavirenz (EFV) and nevirapine (NVP) from water. Results revealed that adsorption of EFV was best fitted to the intraparticle diffusion model, with multi-linearity (multiple adsorption steps). The pseudo-second-order model best describes GW-NVP interaction. Isotherm parameters revealed that Sips and Freundlich model best fit GW-EFV and GW-NVP interactions, with the least value of SSE < 0.04 and 1.27, respectively. GW demonstrated higher adsorption capacity and adsorption maxima for NVP with Kd and qm values of ∼ 2.54 L/g and ∼ 48.31 mg/g, compared to ∼ 1.48 L/g and ∼ 4.41 mg/g obtained for EFV adsorption. Isotherm parameters suggest that GW adsorbed NVP slightly better with stronger binding strength than EFV, with removal efficiencies of 84% (NVP) and 80% (EFV) under optimum conditions. A heterogeneous adsorption mechanism was suggested for GW-EFV sorption, in contrast to a less heterogeneous and multilayer adsorption mechanism for GW-NVP adsorption. NVP adsorption is a spontaneous exothermic process, while GW-EFV interaction is a spontaneous endothermic process. Experimental results were supported by computational studies, which revealed the influence of strong dispersion interactions and H-bonding at specific pH ranges.

Super fine cerium hydroxide abrasives for SiO2 film chemical mechanical planarization performing scratch free

Face-centered-cubic crystallized super-fine (~ 2 nm in size) wet-ceria-abrasives are synthesized using a novel wet precipitation process that comprises a Ce4+ precursor, C3H4N2 catalyst, and NaOH titrant for a synthesized termination process at temperature of at temperature of 25 °C. This process overcomes the limitations of chemical–mechanical-planarization (CMP)-induced scratches from conventional dry ceria abrasives with irregular surfaces or wet ceria abrasives with crystalline facets in nanoscale semiconductor devices. The chemical composition of super-fine wet ceria abrasives depends on the synthesis termination pH, that is, Ce(OH)4 abrasives at a pH of 4.0–5.0 and a mixture of CeO2 and Ce(OH)4 abrasives at a pH of 5.5–6.5. The Ce(OH)4 abrasives demonstrate better abrasive stability in the SiO2-film CMP slurry than the CeO2 abrasives and produce a minimum abrasive zeta potential (~ 12 mV) and a minimum secondary abrasive size (~ 130 nm) at the synthesis termination pH of 5.0. Additionally, the abrasive stability of the SiO2-film CMP slurry that includes super-fine wet ceria abrasives is notably sensitive to the CMP slurry pH; the best abrasive stability (i.e., a minimum secondary abrasive size of ~ 130 nm) is observed at a specific pH (6.0). As a result, a maximum SiO2-film polishing rate (~ 524 nm/min) is achieved at pH 6.0, and the surface is free of stick-and-slip type scratches.

CONCO2 RANDOMIZED CONTROLLED TRIAL INTERIM UPDATE: EMBRYO CULTURE IN A CONTINUOUS CARBON DIOXIDE SETTING DOES NOT NEGATIVELY IMPACT BLASTOCYST FORMATION RATES

A critical parameter of embryo culture during in vitro fertilization (IVF) is culture media pH, which is affected by the composition of the media as well as carbon dioxide (CO2) tension of the surrounding atmosphere. Because use of sequential media requires targeting a specific media pH range for cleavage media and blastocyst media, many labs use an assigned CO2 setting for cleavage culture, and a different CO2 setting for blastocyst culture. Although differing CO2 settings from cleavage to blastocyst culture achieves appropriate pH targets for both, a single CO2 setting can also achieve the appropriate pH target for both media.

Quality assessment of five pharmaceutical products of different brands marketed in Nigeria

Many pharmaceutical products have been reported to be substandard and counterfeit. About 15% of all drugs circulating in some parts of Africa and Asia are believed to be counterfeit, with figures rising to as high as 50%. This study was therefore carried out to assess the quality of five groups of drugs of different brands manufactured by pharmaceutical companies in Nigeria. Qualitative and quantitative analysis were carried out on the drugs using United States, British and Indian Pharmacopoeias. Qualitative analysis investigated includes: friability test, hardness test, disintegration test, dissolution test, pH, and weight uniformity for tablets; specific gravity, flow rate, pH and weight per ml of syrups. The quantitative analysis includes percentage purity and drug assay determination for different constituents using titrimetric, spectrophotometric and high performance liquid chromatographic (HPLC) methods. From the study, it was established that the Nigeria brands of pharmaceutical products sampled generally conformed to the established qualitative and quantitative specifications. There was however a short slight fall in the chromatographic assay for vitamin B6 in the Blood tonic from one company and similarly, the vitamin B1 in the Blood tonic of one company were at variance to those from other companies. The result for the statistical analysis shows that there is uniformity in weight of all tablets analysed and it complies with the specification. Standard pharmaceutical analysis must therefore be regularly carried out on pharmaceutical products before marketing so as to ensure good health, safety, elimination of sub-standard drugs and prevention of over- or under-dosage, which may further affect or cause damage to the health of the users. Consumer’s choice of generics should therefore be based on the analytical results (assay results, bio-pharmaceutical results, and statistical results) of the product and the projected bioequivalence.

Note on Physical and Chemical Properties of Guar Gum in Some Newly Developed Guar(Cyamopsis tetragonolobaL. Taub) Genotypes

This study aimed at determination of the physical and chemical characteristics of guar gum in twenty newly developed guar (Cyamopsis tetragonoloba L. Taub) genotypes. For assessment of the physical properties, data were recorded on refractive index, specific rotation, optical density and relative viscosity. The chemical analysis included gum content, pH and sugar profile. The gum content ranged from 23 – 30.33 %, with a 2.08 ratio of mannose to galactose. The relative viscosity ranged from 2055.17 to 3167.9 centipoises, the highest value was detected in Gm22. Moreover, the values of specific rotation, pH, refractive index and optical density of guar gum ranged from43.33°to 81.67°, 6.15 to 7.13, 1.336 to 1.338 and 0.03 – 0.44%, respectively. It was concluded that a wide range of variability exists among the evaluated genotypes in most of the studied characteristics. Such variation can be exploited in breeding programs for improvement of gum quality.

Characterization of the Chromium (III)-Glycine Complexes in Acidic Medium by UV-Visible Spectroscopy and Capillary Electrophoresis

Since 2017 REACH restrictions on hexavalent chromium, aeronautic industries have been involved in the substitution processes for chromium plating. So far, the use of trivalent chromium-based precursors seems to be the best solution in terms of process adaptation. The development of such process is nested on a better understanding on solution chemistry of the plating bath. More specifically, it is needed to characterize the complexation mechanisms occurring with the chromium (III), since they are responsible for a higher electrodeposition efficiency. Chromium (III) complexation occurs under specific conditions such as acidic solution, where chromium hydrolysis takes place, leading to a stable aqua chromium complex, which is suspected to be detrimental to an even deposit. To tackle this issue, a complexing agent is added to destabilize hexaaquachromium complex. It is reported that ligands as glycine allow the formation of chromium-ligand complexes under specific pH and chromium-ligand ratio. In order to identify, and to understand the formation of the various complexes, two characterization methods have been intended: UV-visible spectroscopy, which allows the identification of chromium complexes through the d-d electronic transition in the UV-Visible range, and capillary electrophoresis, as separation method, coupled to UV-visible detection in order to identify and quantify each species. UV-visible spectroscopy and capillary electrophoresis analyses revealed that no glycine-chromium complex was observed for pH lower than 2, which are the regular condition for electrodeposition. Only a lower Cr:Gly ratio and/or a pH higher than 2 allowed observing glycine-complexes in the solution. As these conditions could be met during electrodeposition nearby the substrate/electrolyte interface, it is highly likely that the chromium depletion together with the pH increase occurring would favor the formation of glycine-complexes at the interface, which were reported to be required to achieve homogeneous chromium deposits.

Physicochemical properties of Honey from Traditional Beekeepers of Sohra

Objective: To determine the physicochemical properties of honey to help ascertain its quality. The properties investigated in the present work are specific gravity, refractive index, moisture content, total solids, pH, free acidity, electrical conductivity, and hydroxymethylfurfural (HMF). Methods/Statistical analysis: To determine properties of honey such as refractive index, moisture content, pH, free acidity, electrical conductivity, and hydroxymethylfurfural, the procedures prescribed by the International Honey Commission were followed. Specific gravity was determined using the method described by Rebiai et al. Total solids was calculated by the formula given by Amin et al. Statistical analyses were carried out in Microsoft Excel 2016, and all readings were presented as mean±standard deviation. Correlation studies were also used wherever applicable. Findings: The moisture content lies in the range (16.6±0.4) g/100g to (19.4±0.3) g/100g. The total solids of all honey samples were above 80%. The pH varies from (3.59±0.02) to (3.73±0.01). The free acidity recorded a minimum of (32.3±1.5) meq/kg and a maximum of (42.0±2.0) meq/kg. The honey samples recorded electrical conductivities between (0.51±0.15) mS/cm and (0.61±0.25) mS/cm. The HMF varies from (8.9±0.2)mg/kg to (34.2±0.2) mg/kg. All the properties that were measured were well within the range prescribed by international agencies responsible for the quality control of Honey. Novelty: Adulteration of honey is a major concern as it affects the health and well being of a person. The recent study by the Centre for Science and Environment, New Delhi which reported adulteration of honey by eight household brands in the Indian market is a cause of alarm. A noteworthy feature of the current study was that it highlighted the superior quality of honey from traditional bee-keepers of Sohra, which even have the potential for export. No adulteration was detected relative to the parameters being investigated. Keywords Sohra, Bee, Honey, Physicochemical properties, Quality, Adulteration

Preparation and characterization of sodium alginate/phosphate-stabilized amorphous calcium carbonate nanocarriers and their application in the release of curcumin

Phosphate-stabilized amorphous calcium carbonate (ACCP) has excellent biocompatibility, bioactivity, and biodegradability, and can be easily synthesized and stored. However, unmodified ACCP, as a controlled drug release carrier, decomposes rapidly in an acidic environment and highly depends on the system’s pH value, which can not meet the need for long-term release of active substances, thus limiting its application scope. To realize the specific pH responsiveness of ACCP nanoparticles, we designed and synthesized monodisperse sodium alginate/ACCP (Alginate/ACCP) composite nanoparticles in this paper. After ultrasonic treatment, nanoparticles with an average particle size less than 200 nm could form stable water dispersion that could be dispersed for up to 10 d. Based on the specific pH sensitivity of sodium alginate, the drug-controlled release performance of composite nanoparticles and the therapeutic effect of drug-loaded nanoparticles on A549 cancer cells were studied. The results indicated that under the same pH condition, the curcumin (Cur) release rate of composite nanoparticles gradually decreased with sodium alginate addition. When the dosage of sodium alginate was 1.0 mg ml−1, the cumulative drug release rate of nanoparticles in 40 h was only about 35%. Besides, the drug-loaded nanoparticles showed the excellent killing ability of cancer cells, and the survival rate of cancer cells decreased in a concentration-dependent manner. Therefore, through reasonable optimization design, we can synthesize composite nanoparticles with excellent sustained-release properties to provide a new strategy for cancer cells’ long-term treatment.

Genetically Encoded, pH-Sensitive mTFP1 Biosensor for Probing Lysosomal pH.

Lysosomes are important sites for macromolecular degradation, defined by an acidic lumenal pH of ∼4.5. To better understand lysosomal pH, we designed a novel, genetically encoded, fluorescent protein (FP)-based pH biosensor called Fluorescence Indicator REporting pH in Lysosomes (FIRE-pHLy). This biosensor was targeted to lysosomes with lysosomal-associated membrane protein 1 (LAMP1) and reported lumenal pH between 3.5 and 6.0 with monomeric teal fluorescent protein 1 (mTFP1), a bright cyan pH-sensitive FP variant with a pKa of 4.3. Ratiometric quantification was enabled with cytosolically oriented mCherry using high-content quantitative imaging. We expressed FIRE-pHLy in several cellular models and quantified the alkalinizing response to bafilomycin A1, a specific V-ATPase inhibitor. In summary, we have engineered FIRE-pHLy, a specific, robust, and versatile lysosomal pH biosensor, that has broad applications for investigating pH dynamics in aging- and lysosome-related diseases, as well as in lysosome-based drug discovery.

Transparent Ion-Exchange Membrane Exhibiting Intense Emission under a Specific pH Condition Based on Polypyridyl Ruthenium(II) Complex with Two Imidazophenanthroline Groups.

The development and the photophysical behavior of a transparent ion-exchange membrane based on a pH-sensitive polypyridyl ruthenium(II) complex, [(bpy)2RuII(H2bpib)RuII(bpy)2](ClO4)4 (bpy = 2,2′-bipyridine, H2bpib = 1,4-bis([1,10]phenanthroline[5,6-d]-imidazol-2-yl)benzene), are experimentally and theoretically reported. The emission spectra of [(bpy)2RuII(H2bpib)RuII(bpy)2]@Nafion film were observed between pH 2 and pH 11 and showed the highest relative emission intensity at pH 5 (λmaxem = 594.4 nm). The relative emission intensity of the film significantly decreased down to 75% at pH 2 and 11 compared to that of pH 5. The quantum yields (Φ) and lifetimes (τ) showed similar correlations with respect to pH, Φ = 0.13 and τ = 1237 ns at pH 5, and Φ = 0.087 and τ = 1014 ns and Φ = 0.069 and τ = 954 ns at pH 2 and pH 11, respectively. These photophysical data are overall considerably superior to those of the solution, with the radiative- (kr) and non-radiative rate constants (knr) at pH 5 estimated to be kr = 1.06 × 105 s−1 and knr = 7.03 × 105 s−1. Density functional theory calculations suggested the contribution of ligand-to-ligand- and intraligand charge transfer to the imidazolium moiety in Ru-H3bpib species, implying that the positive charge on the H3bpib ligand works as a quencher. The Ru-Hbpib species seems to enhance non-radiative deactivation by reducing the energy of the upper-lying metal-centered excited state. These would be responsible for the pH-dependent “off-on-off” emission behavior.

Chitosan/Agarose‐g‐poly (methacrylate) pH responsive polymeric blend: A dais for controlled delivery of Capecitabine

AbstractThis project was designed to develop pH responsive smart chitosan/agarose‐g‐poly (methacrylate) hydrogels using free radical polymerization for targeted delivery of Capecitabine (a prodrug of 5‐fluorouracil) for the treatment of colorectal cancer. Developed hydrogels were evaluated for drug loading efficiency, thermal stability, compatibility of components, morphology, swelling behavior, release kinetics and acute oral toxicity studies in rabbits. Moreover, pharmacokinetic parameters were also measured in healthy rabbits. Structural entanglement was confirmed via FTIR providing evidence of hydrogel formation. Loading of Capecitabine was in range from 60.35% to 62.57%. Hydrogels showed pH‐responsive behavior by providing maximum swelling of 93.84% at pH 7.4 identical to colon. Release of Capecitabine from hydrogels was in controlled pattern over a period of 36 h. Toxicity studies revealed no signs of ocular, dermal and oral toxicity providing safety evidence of hydrogels. In addition, pharmacokinetic evaluations of Capecitabine loaded hydrogels showed significant increase in plasma half‐life of 17 h and AUC of 57.65 μg.h/ml in comparison to pure Capecitabine solution. Therefore, these results strongly suggest that newly formed hydrogels are biocompatible, capable of providing sustained release at specific pH and can be employed as a cargo for colorectal delivery.