ABSTRACT
Highly efficient anti-Stokes (AS) photoluminescence (PL) is observed from halide perovskite quantum dots (QDs) due to their strong electron-phonon interactions. The AS PL is particularly intriguing, as it suggests the potential for semiconductor optical cooling if the external quantum efficiency approaches 100%. However, the PL quantum efficiency in QDs is primarily dominated by multiparticle nonradiative Auger recombination processes under intense photoexcitation, which impose limits on the optical cooling gain. Here, we investigate the Auger recombination of dot-in-crystal perovskites. We quantitatively estimate the maximum optical cooling gain and the corresponding excitation intensity. We further conducted optical cooling experiments and demonstrate a maximum photocooling of approximately 9 K from room temperature. Additionally, we confirmed that increasing the excitation intensity leads to a transition from photocooling to photoheating. These observations are consistent with our time-resolved measurements, offering insights into the potential and limitations of optical cooling in semiconductor QDs.
ABSTRACT
Poloxamer hydrogel possesses thermosensitive sol-gel transition characteristics and is widely used as a drug-controlled-release carrier for topical or injectable formulations. In this study, the effect of loading of a drug, acetaminophen (ACE), on the physical and structural properties of poloxamer 407 (P407) micelles and hydrogels was investigated. Differential scanning calorimetry measurements revealed that ACE reduced the critical micelle temperature and enthalpy of micellization of P407 solutions. The P407 micellization was promoted by ACE incorporation. Rheometry showed that ACE increased the sol-gel transition temperature and reduced the gel strength of P407. In situ small-angle X-ray scattering (SAXS) using synchrotron radiation revealed that ACE altered the structure of P407 micelles and their packing in the P407 gels. As ACE concentration increased, the P407 micelle packing changed from a face-centered cubic phase to a body-centered cubic phase. Furthermore, ACE disordered the micelle packing structure and induced the formation of an amorphous phase. Structural analysis of the P407 micelle packing indicated that ACE reduced the aggregation number (Nagg) of P407 micelles in the gels. The SAXS study for diluted P407 solutions revealed that ACE reduced the P407 micelle size and its uniformity. The structural changes in P407 micelles by ACE loading (e.g., the reduction of Nagg, size, and size uniformity) would alter the micelle packing structure. It was found that these structural changes of micelle packing, especially the formation of an amorphous phase, could destabilize the P407 gel. As a result, the physical properties of P407 gels, such as gelation temperature and gel strength, were changed. This relationship between the structure and physical property of drug-loaded P407 gels was well-explained by correlating the micelle and gel structures. The mechanistic understanding of the change in the physical properties of P407 gels by drug loading is essential for the effective development of poloxamer gel formulations.
ABSTRACT
Poloxamer 407 (P407) is used as a safety-guaranteed, invaluable pharmaceutical nanocarrier. The aqueous solution of P407 exhibits sol-to-gel and gel-to-sol transitions, specifically during a temperature rise. Here, we develop a method to determine the pair potential between colloidal particles based primarily on experimental small-angle scattering data. Using this approach, the pair potential between the P407 micelles in the sol-gel-sol transition state is revealed without prelimiting any type of interaction forces. The results indicate that the increase in the attractive interaction contributes to enhancing the volume fraction, which is the decisive parameter for the gelation in terms of the Alder transition theory, i.e., the fluid-to-crystal phase transition of the hard-sphere model in the micelle system. This study demonstrates that one of the key mechanisms of the gel-to-sol transition upon heating is the enhancement of the structural fluctuation due to widening of the potential well in the intermicellar pair potential.
ABSTRACT
Mosquito-borne diseases account for nearly 1 million human deaths annually, yet we have a limited understanding of developmental events that influence host-seeking behavior and pathogen transmission in mosquitoes. Mosquito-borne pathogens are transmitted during blood meals, hence adult mosquito behavior and physiology have been intensely studied. However, events during larval development shape adult traits, larvae respond to many of the same sensory cues as adults, and larvae are susceptible to infection by many of the same disease-causing agents as adults. Hence, a better understanding of larval physiology will directly inform our understanding of physiological processes in adults. Here, we use single cell RNA sequencing (scRNA-seq) to provide a comprehensive view of cellular composition in the Aedes aegypti larval ventral nerve cord (VNC), a central hub of sensory inputs and motor outputs which additionally controls multiple aspects of larval physiology. We identify more than 35 VNC cell types defined in part by neurotransmitter and neuropeptide expression. We also explore diversity among monoaminergic and peptidergic neurons that likely control key elements of larval physiology and developmental timing, and identify neuroblasts and immature neurons, providing a view of neuronal differentiation in the VNC. Finally, we find that larval cell composition, number, and position are preserved in the adult abdominal VNC, suggesting studies of larval VNC form and function will likely directly inform our understanding adult mosquito physiology. Altogether, these studies provide a framework for targeted analysis of VNC development and neuronal function in Aedes aegypti larvae.
Subject(s)
Aedes , Ascomycota , Animals , Humans , Aedes/genetics , Larva , NeuronsABSTRACT
Solid-solution-type Au-Pt alloy nanoparticles (NPs) were prepared from the nanoclusters of each metal using the polymer-conjugated fusion growth method. The elemental mapping analysis showed that the mixing state of the elements in the NPs drastically changed in the narrow reaction-temperature range from 100 °C to 180 °C. For their various mixing states, the 5d-states of Au and Pt atoms in the alloy NPs were investigated on the basis of the white line intensities of X-ray absorption near edge structure (XANES). Then, the 5d-states of Au and Pt atoms in a model crystalline ordered alloy structures were investigated on the basis of the theoretically calculated XANES spectra using density functional theory (DFT) in the whole composition range. The DFT calculation showed that the changes in the absorption spectra near the Pt and Au edges are caused by the change in the occupation of the Pt 5d-states and the orbital hybridisation of the Au 5d-states with the 5d-states of neighbouring Pt atoms around an Au atom, respectively.
ABSTRACT
BACKGROUND: Several large-scale studies have assessed endovascular and surgical treatment methods for nonocclusive mesenteric ischemia (NOMI); however, the prognostic factors for NOMI remain unclear. Therefore, this study aimed to evaluate risk factors for in-hospital mortality among patients with NOMI who underwent laparotomy and to examine therapeutic strategies that may improve the prognosis. MATERIALS AND METHODS: In this multicenter retrospective study, the authors reviewed the electronic medical records retrieved from the inpatient database of patients with NOMI at eight district general hospitals between January 2011 and January 2021. A total of 88 patients who underwent laparotomies were divided into survivor and nonsurvivor groups, and statistical analysis was performed to determine clinical and physiological factors. RESULTS: Exploratory laparotomy based on second-look surgery was the first treatment choice. The overall mortality rate was 48.8%, with a male-to-female ratio of 1.1:1. The median Sequential Organ Failure Assessment (SOFA) score was 8 [interquartile range: 3.75-14.2], and the median SOFA scores were 5 [3-7] in the survivor group and 13 [9-17.5] in the nonsurvivor group. Univariate analysis revealed a significant difference in BMI ( P <0.001), hypoglycemia ( P =0.0012), previous cardiovascular surgery ( P =0.0019), catecholamine use ( P <0.001), SOFA score ( P <0.001), platelet count ( P =0.0023), and lactate level ( P <0.001). Logistic regression analysis using the factors with significant differences revealed that SOFA score ≥10 (odds ratio 23.3; 95% CI: 1.94-280.00; P =0.013) was an independent prognostic factor. In addition, catecholamine use was suggested as a factor with a SOFA score greater than or equal to 10. CONCLUSION: This study confirmed that a SOFA score of greater than or equal to 10 may be associated with increased mortality. While closely monitoring low blood pressure and renal dysfunction, survival rates may be improved if surgical intervention is performed before the SOFA score reaches greater than or equal to 10.
Subject(s)
Mesenteric Ischemia , Organ Dysfunction Scores , Humans , Male , Female , Prognosis , Retrospective Studies , Mesenteric Ischemia/diagnosis , Mesenteric Ischemia/surgery , CatecholaminesABSTRACT
Alcohols and urea are widely used as effective protein denaturants. Among monohydric alcohols, 2,2,2-trifluoroethanol (TFE) has large cosolvent effects as a helix stabilizer in proteins. In contrast, urea efficiently denatures ordered native structures, including helices, into coils. These opposing cosolvent effects of TFE and urea are well known, even though both preferentially bind to proteins; however, the underlying molecular mechanism remains controversial. Cosolvent-dependent relative stability between native and denatured states is rigorously related to the difference in preferential binding parameters (PBPs) between these states. In this study, GCN4-p1 with two-stranded coiled coil helices was employed as a model protein, and molecular dynamics simulations for the helix dimer and isolated coil were conducted in aqueous solutions with 2 M TFE and urea. As 2 M cosolvent aqueous solutions did not exhibit clustering of cosolvent molecules, we were able to directly investigate the molecular origin of the excess PBP without considering the enhancement effect of PBPs arising from the concentration fluctuations. The calculated excess PBPs of TFE for the helices and those of urea for the coils were consistent with experimentally observed stabilization of helix by TFE and that of coil by urea. The former was caused by electrostatic interactions between TFE and side chains of the helices, while the latter was attributed to both electrostatic and dispersion interactions between urea and the main chains. Unexpectedly, reverse-micelle-like orientations of TFE molecules strengthened the electrostatic interactions between TFE and the side chains, resulting in strengthening of TFE solvation.
Subject(s)
Protein Folding , Trifluoroethanol , Trifluoroethanol/pharmacology , Urea/pharmacology , Ethanol , Water , Circular DichroismABSTRACT
Mpox virus (formerly monkeypox virus [MPXV]) is a neglected zoonotic pathogen that caused a worldwide outbreak in May 2022. Given the lack of an established therapy, the development of an anti-MPXV strategy is of vital importance. To identify drug targets for the development of anti-MPXV agents, we screened a chemical library using an MPXV infection cell assay and found that gemcitabine, trifluridine, and mycophenolic acid (MPA) inhibited MPXV propagation. These compounds showed broad-spectrum anti-orthopoxvirus activities and presented lower 90% inhibitory concentrations (0.026 to 0.89 µM) than brincidofovir, an approved anti-smallpox agent. These three compounds have been suggested to target the postentry step to reduce the intracellular production of virions. Knockdown of IMP dehydrogenase (IMPDH), the rate-limiting enzyme of guanosine biosynthesis and a target of MPA, dramatically reduced MPXV DNA production. Moreover, supplementation with guanosine recovered the anti-MPXV effect of MPA, suggesting that IMPDH and its guanosine biosynthetic pathway regulate MPXV replication. By targeting IMPDH, we identified a series of compounds with stronger anti-MPXV activity than MPA. This evidence shows that IMPDH is a potential target for the development of anti-MPXV agents. IMPORTANCE Mpox is a zoonotic disease caused by infection with the mpox virus, and a worldwide outbreak occurred in May 2022. The smallpox vaccine has recently been approved for clinical use against mpox in the United States. Although brincidofovir and tecovirimat are drugs approved for the treatment of smallpox by the U.S. Food and Drug Administration, their efficacy against mpox has not been established. Moreover, these drugs may present negative side effects. Therefore, new anti-mpox virus agents are needed. This study revealed that gemcitabine, trifluridine, and mycophenolic acid inhibited mpox virus propagation and exhibited broad-spectrum anti-orthopoxvirus activities. We also suggested IMP dehydrogenase as a potential target for the development of anti-mpox virus agents. By targeting this molecule, we identified a series of compounds with stronger anti-mpox virus activity than mycophenolic acid.
Subject(s)
Monkeypox virus , Mycophenolic Acid , Guanosine/pharmacology , IMP Dehydrogenase/genetics , IMP Dehydrogenase/metabolism , Mycophenolic Acid/pharmacology , Trifluridine , Monkeypox virus/drug effectsABSTRACT
BACKGROUND: Mpox virus (MPXV) is a zoonotic orthopoxvirus and caused an outbreak in 2022. Although tecovirimat and brincidofovir are approved as anti-smallpox drugs, their effects in mpox patients have not been well documented. In this study, by a drug repurposing approach, we identified potential drug candidates for treating mpox and predicted their clinical impacts by mathematical modeling. METHODS: We screened 132 approved drugs using an MPXV infection cell system. We quantified antiviral activities of potential drug candidates by measuring intracellular viral DNA and analyzed the modes of action by time-of-addition assay and electron microscopic analysis. We further predicted the efficacy of drugs under clinical concentrations by mathematical simulation and examined combination treatment. RESULTS: Atovaquone, mefloquine, and molnupiravir exhibited anti-MPXV activity, with 50% inhibitory concentrations of 0.51-5.2 µM, which was more potent than cidofovir. Whereas mefloquine was suggested to inhibit viral entry, atovaquone and molnupiravir targeted postentry processes. Atovaquone was suggested to exert its activity through inhibiting dihydroorotate dehydrogenase. Combining atovaquone with tecovirimat enhanced the anti-MPXV effect of tecovirimat. Quantitative mathematical simulations predicted that atovaquone can promote viral clearance in patients by 7 days at clinically relevant drug concentrations. CONCLUSIONS: These data suggest that atovaquone would be a potential candidate for treating mpox.
Subject(s)
Mefloquine , Monkeypox virus , Humans , Atovaquone/pharmacology , Atovaquone/therapeutic use , Mefloquine/pharmacology , Mefloquine/therapeutic use , Monkeypox virus/drug effectsABSTRACT
OBJECTIVE: Interstitial and intracavitary ultra- sound applicators had been developed and studied for minimally invasive treatments (MIT). However, the acoustic outputs are limited by the small-size PZT. We therefore studied the acoustic waveguide (AW) applicator which enables the use of a large-size PZT, and we aimed to advance AW applicators towards thermal ablation applications. METHODS: Double parabolic reflectors wave-guided ultrasonic transducer (DPLUS) was introduced which has two parabolic reflectors for enhancing the acoustic output. Theoretical modeling was conducted for optimizing the DPLUS thin waveguide. RESULTS: Modeling results showed that optimal a/Λ (thin waveguide radius/wavelength) can be found and the optimal a depends on the excitable vibration amplitude in the thin waveguide. A local optimal a/Λ= 0.2392 was considered the best choice, which results in the optimal frequency of 2.2 MHz at the radius a of 0.6 mm. To verify this optimal frequency, experiments under two working frequencies of 1.0282 MHz and 2.2579 MHz were conducted. Temperature rise curves in the chicken breast tissue showed good agreements between experiments and modeling results, which proved the effectiveness of the modeling. In addition, experiments showed an ablated area with a diameter of 1.03±0.12 mm under continuous excitation of 2.2579 MHz and 5 s. CONCLUSION: The developed DPLUS advanced the AW applicators towards thermal ablation applications. SIGNIFICANCE: This study provides the evidence for recognizing AW applicators as a technique for thermal ablation.
Subject(s)
Ultrasonic Therapy , Ultrasonics , Ultrasonic Therapy/methods , Temperature , Acoustics , Transducers , Equipment DesignABSTRACT
Some people are more attractive to mosquitoes than others, but the mechanistic basis of this phenomenon is poorly understood. We tested mosquito attraction to human skin odor and identified people who are exceptionally attractive or unattractive to mosquitoes. These differences were stable over several years. Chemical analysis revealed that highly attractive people produce significantly more carboxylic acids in their skin emanations. Mutant mosquitoes lacking the chemosensory co-receptors Ir8a, Ir25a, or Ir76b were severely impaired in attraction to human scent, but retained the ability to differentiate highly and weakly attractive people. The link between elevated carboxylic acids in "mosquito-magnet" human skin odor and phenotypes of genetic mutations in carboxylic acid receptors suggests that such compounds contribute to differential mosquito attraction. Understanding why some humans are more attractive than others provides insights into what skin odorants are most important to the mosquito and could inform the development of more effective repellents.
Subject(s)
Aedes , Anopheles , Insect Repellents , Animals , Humans , Carboxylic Acids/pharmacology , Odorants/analysis , Insect Repellents/pharmacology , Insect Repellents/analysisABSTRACT
Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, causes adult T-cell leukemia-lymphoma, HTLV-1 associated myelopathy/tropical spastic paraparesis, and HTLV-1 uveitis. Currently, no antiretroviral therapies or vaccines are available for HTLV-1 infection. This study aimed to develop an antibody against the HTLV-1 envelope protein (Env) and apply it to a near-infrared photoimmuno-antimicrobial strategy (NIR-PIAS) to eliminate HTLV-1 infected cells. We established mouse monoclonal antibodies (mAbs) against HTLV-1 Env by immunization with a complex of liposome and the recombinant protein. Detailed epitope mapping revealed that one of the mAbs bound to the proline-rich region of gp46 and exhibited no obvious neutralizing activity to inhibit viral infection. Instead, the mAb was rarely internalized intracellularly and remained on the cell surface of HTLV-1-infected cells. The antibody conjugated to the photosensitive dye IRDye700Dx recognized HTLV-1 infected cells and killed them following NIR irradiation. These results suggest that the novel mAb and NIR-PIAS could be developed as a new targeted therapeutic tool against HTLV-1 infected cells.
Subject(s)
Human T-lymphotropic virus 1 , Mice , Animals , Humans , Retroviridae Proteins, Oncogenic , Antibodies, Monoclonal , Liposomes , Gene Products, env , Recombinant Proteins , Glycoproteins , ProlineABSTRACT
A mixture of poly(benzyl methacrylate) (PBnMA) and 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide ([C2mim][NTf2]) exhibits lower-critical-solution-temperature (LCST)-type phase separation. An investigation combining magic-angle spinning NMR spectroscopy and small-angle scattering was performed to gain new insights into the interaction between PBnMA and the ionic liquid. The molecular mobility and the solute-solvent interaction in the system were investigated using 1H high-resolution magic-angle spinning NMR. Applying a magic-angle spinning frequency of 2 kHz allowed identifying the PBnMA peaks, which were not observed by conventional solution-state NMR. The peaks of [C2mim]+ almost coincided in the presence and absence of PBnMA, indicating the decoupling of the bulk solvent and polymer. The conformational state of PBnMA in [C2mim][NTf2] was investigated using small-angle X-ray scattering (SAXS). The pair distribution functions of PBnMA chains calculated from SAXS profiles suggest that PBnMA adopts a random coil conformation upon dissolution in [C2mim][NTf2]. The combined study clarifies the decoupled low mobility of polymers with a random coil conformation. It is considered that the specific decoupled low mobility is one of the origins of the decoupling conductivity of [C2mim][NTf2] in a matrix polymer. In addition, an increase in temperature induced a downfield shift and broadening of the [C2mim]+ peaks, suggesting that a larger amount of [C2mim]+ was bound to the PBnMA chains even at temperatures approaching the LCST.
Subject(s)
Ionic Liquids , Ionic Liquids/chemistry , Amides , Scattering, Small Angle , X-Rays , X-Ray Diffraction , Magnetic Resonance Spectroscopy/methods , Solvents , Polymers/chemistryABSTRACT
Aedes aegypti mosquitoes are a persistent human foe, transmitting arboviruses including dengue when they feed on human blood. Mosquitoes are intensely attracted to body odor and carbon dioxide, which they detect using ionotropic chemosensory receptors encoded by three large multi-gene families. Genetic mutations that disrupt the olfactory system have modest effects on human attraction, suggesting redundancy in odor coding. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. We discovered that Ae. aegypti uses a different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes. In vivo electrophysiology demonstrates that the broad ligand-sensitivity of mosquito olfactory neurons depends on this non-canonical co-expression. The redundancy afforded by an olfactory system in which neurons co-express multiple chemosensory receptors may increase the robustness of the mosquito olfactory system and explain our long-standing inability to disrupt the detection of humans by mosquitoes.
Subject(s)
Aedes , Olfactory Receptor Neurons , Aedes/genetics , Animals , Humans , Ligands , OdorantsABSTRACT
The spike protein (SP) of SARS-CoV-2 is an important target for COVID-19 therapeutics and vaccines as it binds to the ACE2 receptor and enables viral infection. Rapid production and functional characterization of properly folded SP is of the utmost importance for studying the immunogenicity and receptor-binding activity of this protein considering the emergence of highly infectious viral variants. In this study, we attempted to express the receptor-binding region (RBD) of SARS-CoV-2 SP containing disulfide bonds using the wheat germ cell-free protein synthesis system. By adding protein disulfide isomerase (PDI) and endoplasmic reticulum oxidase (ERO1α) to the translational reaction mixture, we succeeded in synthesizing a functionally intact RBD protein that can interact with ACE2. Using this RBD protein, we have developed a high-throughput AlphaScreen assay to evaluate the RBD-ACE2 interaction, which can be applied for drug screening and mutation analysis. Thus, our method sheds new light on the structural and functional properties of SARS-CoV-2 SP and has the potential to contribute to the development of new COVID-19 therapeutics.
Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Disulfides , Peptidyl-Dipeptidase A/metabolism , Protein Binding , Spike Glycoprotein, Coronavirus , TriticumABSTRACT
The continuous emergence of microbial pathogens for which there are no effective antimicrobials threatens global health, necessitating novel antimicrobial approaches. Here, we present a targeted antimicrobial strategy that can be applied to various microbial pathogens. A photoimmuno-conjugate composed of an antibody against the target pathogen and a photoplastic phthalocyanine-derivative probe that generates photo-induced mechanical stress was developed based on photoimmuno-technology. This strategy, named as photoimmuno-antimicrobial strategy (PIAS), eliminates targeted pathogens, regardless of the target species or drug-resistance status. Specifically, PIAS acts on a broad range of microbes, including the bacterial pathogen Staphylococcus aureus, fungal pathogen Candida albicans, including their drug-resistant strains, and viral pathogen SARS-CoV-2, the causative agent of COVID-19. Furthermore, PIAS protects mice from fatal infections without damaging the non-targeted host microbiota and tissues. This study may contribute to the development of next-generation anti-infective therapies.
Subject(s)
Anti-Infective Agents , COVID-19 Drug Treatment , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Bacteria , Mice , SARS-CoV-2ABSTRACT
BACKGROUND: Currently, revisions to the ICH S1 guidance on rodent carcinogenicity testing are being proposed. Application of this approach would reduce the use of animals in accordance with the 3Rs principles (reduce/refine/replace). The method would also shift resources to focus on more scientific mechanism-based carcinogenicity assessments and promote safe and ethical development of new small molecule pharmaceuticals. In the revised draft, findings such as cellular hypertrophy, diffuse and/or focal cellular hyperplasia, persistent tissue injury and/or chronic inflammation, preneoplastic changes, and tumors are listed as histopathology findings of particular interest for identifying carcinogenic potential. In order to predict hepatocarcinogenicity of test chemicals based on the results from 2- or 4-week repeated dose studies, we retrospectively reanalyzed the results of a previous collaborative study on the liver micronucleus assay. We focused on liver micronucleus induction in combination with histopathological changes including hypertrophy, proliferation of oval cells or bile duct epithelial cells, tissue injuries, regenerative changes, and inflammatory changes as the early responses of hepatocarcinogenesis. For these early responses, A total of 20 carcinogens, including 14 genotoxic hepatocarcinogens (Group A) and 6 non-liver-targeted genotoxic carcinogens (Group B) were evaluated. RESULTS: In the Group A chemicals, 5 chemicals (NPYR, MDA, NDPA, 2,6-DNT, and NMOR) showed all of the 6 early responses in hepatocarcinogenesis. Five chemicals (DMN, 2,4-DNT, QUN, 2-AAF, and TAA) showed 4 responses, and 4 chemicals (DAB, 2-NP, MCT, and Sudan I) showed 3 responses. All chemicals exhibited at least 3 early responses. Contrarily, in the Group B chemicals (6 chemicals), 3 of the 6 early responses were observed in 1 chemical (MNNG). No more than two responses were observed in 3 chemicals (MMC, MMS, and KA), and no responses were observed in 2 chemicals (CP and KBrO3). CONCLUSION: Evaluation of liver micronucleus induction in combination with histopathological examination is useful for detecting hepatocarcinogens. This assay takes much less time than routine long-term carcinogenicity studies.
ABSTRACT
To realize compact and portable hemolysis devices, an ultrasonic transducer with a blood channel is proposed in this study. Ultrasound waves are focused by a parabolic reflector to generate high sound pressure inside the channel for hemolysis. The hemolysis performance of the transducer is evaluated using simulations and experiments. Experiments are performed with various voltages and flow rates to verify the feasibility of hemolysis. The hemolysis rate is more than 93% at an applied voltage of 80 Vp-p, a flow rate of 0.25 mL/min, and a driving frequency of 1.28 MHz.
Subject(s)
Hemolysis , Ultrasonics , Humans , Sound , TransducersABSTRACT
The effects of pH changes and saccharin (SAC) addition on the nanostructure and mobility of the cationic aminoalkyl methacrylate copolymer Eudragit E PO (EUD-E) and its drug solubilization ability were investigated. Small-angle X-ray scattering performed using synchrotron radiation and atomic force microscopy showed that the EUD-E nanostructure, which has a size of approximately several nanometers, changed from a random coil structure at low pH (pH 4.0-5.0) to a partially folded structure at high pH (pH 5.5-6.5). The EUD-E also formed a partially folded structure in a wide pH range of 4.5-6.5 when SAC was present, and the coil-to-globule transition was moderate with pH increase, compared with that when SAC was absent. The equilibrium solubility of the neutral drug naringenin (NAR) was enhanced in the EUD-E solution and further increased as the pH increased. The enlargement of the hydrophobic region of EUD-E in association with the coil-to-globule transition led to efficient solubilization of NAR. The interaction with SAC enhanced the mobility of the EUD-E chains in the hydrophobic region of EUD-E, resulting in changes in the drug-solubilizing ability. 1H high-resolution magic-angle spinning NMR measurements revealed that the solubilized NAR in the partially folded structure of EUD-E showed higher molecular mobility in the presence of SAC than in the absence of SAC. This study highlighted that solution pH and the presence of SAC significantly changed the drug solubilization ability of EUD-E, followed by changes in the EUD-E nanostructure, including its hydrophobic region.