Sonodynamic therapy-based nanoplatforms for combating bacterial infections.

The rapid spread and uncontrollable evolution of antibiotic-resistant bacteria have already become urgent global to treat bacterial infections. Sonodynamic therapy (SDT), a noninvasive and effective therapeutic strategy, has broadened the way toward dealing with antibiotic-resistant bacteria and biofilms, which base on ultrasound (US) with sonosensitizer. Sonosensitizer, based on small organic molecules or inorganic nanoparticles, is essential to the SDT process. Thus, it is meaningful to design a sonosensitizer-loaded nanoplatform and synthesize the nanoplatform with an efficient SDT effect. In this review, we initially summarize the probable SDT-based antibacterial mechanisms and systematically discuss the current advancement in different SDT-based nanoplatform (including nanoplatform for organic small-molecule sonosensitizer delivery and nanoplatform as sonosensitizer) for bacterial infection therapy. In addition, the biomedical applications of SDT-involved multifunctional nanoplatforms are also discussed. We believe the innovative SDT-based nanoplatforms would become a highly efficient next-generation noninvasive therapeutic tool for combating bacterial infection.

Development of highly stable ICG-polymeric nanoparticles with ultra-high entrapment efficiency using supercritical antisolvent (SAS)-combined solution casting process.

Indocyanine green (ICG), a water-soluble near-infrared (NIR) photosensitizer, has been enormously regarded in tumor diagnosis and phototherapy. Although tremendous progress in establishing the nanocarrier-based delivery systems has been explored, several limitations of low ICG encapsulation and sophisticated fabrication process remain significant challenges in producing nanoplatforms, limiting the theranostic outcomes of ICG. According to the unique advantages of the supercritical antisolvent (SAS) process and solution casting method, a novel combination approach to obtain the ICG-loaded nanoparticles (ICG-PLO NPs) is demonstrated, in which SAS assisted-ICG nanoparticles (ICG NPs) are coated with polypeptide poly-l-ornithine (PLO) using solution casting approach. This unique nanoplatform with ultra-high drug encapsulation efficiency remarkably improved the aqueous and photothermal stability of ICG. Notably, the coating of PLO could improve the internalization level in cells and anticancer effect in vivo, comprehensively augmenting the cancer phototherapy effect of ICG. Together, the findings of novel particle formation by integrated strategy would certainly broaden the applications of supercritical fluid (SCF) technology, potentiating the design of nano-formulations of ICG for clinical translation.

Preparation of aripiprazole-poly(methyl vinyl ether-co-maleic anhydride) nanocomposites via supercritical antisolvent process for improved antidepression therapy.

Aripiprazole (ARI), a second-generation atypical antipsychotic drug approved for schizophrenia treatment, shows good efficacy against depression. However, the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects, seriously limiting its application in pharmaceutics. Herein, we demonstrated the fabrication of ARI and poly (methyl vinyl ether-co-maleic anhydride) (PVMMA) composite nanoparticles (PA NPs) using the supercritical antisolvent (SAS) process for enhancing its water-solubility and curative anti-depressant effects. Initially, the optimal experimental conditions (ARI/PVMMA mass ratio of 1:6, pressure of 10 MPa, and solution flow rate of 0.75 ml min-1) were determined by a 23 factorial experimental design, resulting in the PA NPs with an excellent particle morphology. In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide (LPS). Similarly, mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior. Importantly, compared with free ARI, the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs. Together, the innovative PA NPs designed by SAS process might provide a candidate for developing new ARI-based nano-formulations.

Synergistic chemo-/photothermal therapy based on supercritical technology-assisted chitosan-indocyanine green/luteolin nanocomposites for wound healing.

Despite the success, it is highly challenging to battle against pathogenic biofilms-based chronic bacterial infections by conventional antibiotic therapy. Herein, we report a near-infrared (NIR)/acid-induced nanoplatform based on chitosan (CS)-coated indocyanine green (ICG, photosensitizer)/luteolin (LUT, a natural quorum sensing inhibitor) nanocomposites (ICG/LUT-CS) as antibacterial and antibiofilm agents for skin wound healing. Initially, the ICG/LUT nanoplatforms are prepared by the supercritical antisolvent technology and coated with the CS layer. The obtained ICG/LUT-CS with ultra-high encapsulation efficiency exhibited more favorable photothermal conversion effects and improved NIR laser/acid dual-induced drug release behavior than individual modalities, achieving exceptional bacteria-killing and biofilm elimination effects. Moreover, the ICG/LUT-CS realized the synergetic effects of chemotherapy and photothermal therapy outcomes for wound healing. Together, our findings provided an appealing strategy for the rapid preparation and future translational application of ICG/LUT-CS as an ideal agent for fighting against biofilm infections.

Supercritical fluid (SCF)-assisted fabrication of carrier-free drugs: An eco-friendly welcome to active pharmaceutical ingredients (APIs).

Despite the success in developing various pharmaceutical formulations, most of the active pharmaceutical ingredients (APIs)/drugs, according to the Biopharmaceutics Classification System (BCS), often suffer from various intrinsic limitations of solubility and permeability, substantially hindering their bioavailability in vivo. Regardless of the fact that the availability of different particle fabrication approaches (top-down and bottom-up) towards pharmaceutical manufacturing, the supercritical fluid (SCF) technology has emerged as one of the highly effective substitutes due to the environmentally benign nature and processing convenience, as well as the economically promising character of SCFs. The exceptional features of SCFs have endowed the fabrication of various APIs either solely or in combination with the compatible supramolecular species towards achieving improved drug delivery. Operating such APIs in high-pressure conditions often results in arbitrary-sized particulate forms, ranging from micron-sized to sub-micron/nano-sized particles. Comparatively, these SCF-processed particles offer enhanced tailorable physicochemical and morphological properties (size, shape, and surface), as well as improved performance efficacy (bioavailability and therapy) over the unprocessed APIs. Although the "carrier-based" delivery is practical among diverse delivery systems, the direct fabrication of APIs into suitable particulate forms, referred to as "carrier-free" delivery, has increased attention towards improving the bioavailability and conveying a high payload of the APIs. This review gives a comprehensive emphasis on the SCF-assisted fabrication of diverse APIs towards exploring their great potential in drug delivery. Initially, we discuss various challenges of drug delivery and particle fabrication approaches. Further, different supercritical carbon dioxide (SC-CO2)-based fabrication approaches depending on the character of SCFs are explicitly described, highlighting their advantages and suitability in processing diverse APIs. Then, we provide detailed insights on various processing factors affecting the properties and morphology of SCF-processed APIs and their pharmaceutical applications, emphasizing their performance efficacy when administered through multiple routes of administration. Finally, we summarize this compilation with exciting perspectives based on the lessons learned so far and moving forward in terms of challenges and opportunities in the scale-up and clinical translation of these drugs using this innovative technology.

Advances in Indocyanine Green-Based Codelivery Nanoplatforms for Combinatorial Therapy.

Indocyanine green (ICG), a near-infrared (NIR) agent with an excellent imaging performance, has captivated enormous interest from researchers owing to its excellent therapeutic and imaging abilities. Although various nanoplatforms-based drug delivery systems (DDS) with the ability to overcome the clinical limitations of ICG has been reported, ICG-medicated conventional cancer diagnosis and photorelated therapies still lack in exhibiting the therapeutic efficacy, resulting in incomplete or partly tumor elimination. In the view of addressing these concerns, various DDSs have been engineered for the efficient codelivery of combined therapeutic agents with ICG, aiming to achieve promising therapeutic results due to multifunctional imaging-guided synergistic antitumor effects. In this article, we will systematically review currently available nanoplatforms based on polymers, inorganic, proteins, and metal-organic frameworks (MOFs), among others, for codelivery of ICG along with other therapeutic agents, providing a foundation for future clinical development of ICG. In addition, codelivery systems for ICG and different mechanism-based therapeutic agents will be illustrated. In summary, we conclude the review with the challenges and perspectives of ICG-based versatile nanoplatforms in detail.

[A Study of the Relationship Between Job Satisfaction and Work Engagement of Physicians in Public Hospitals].

OBJECTIVE: To understand the level of job satisfaction and work engagement of physicians in public hospitals, to analyze the interaction between job satisfaction and work engagement, and to discuss how each dimension of job satisfaction affects work engagement so as to provide information and reference for improving the level of work engagement of physicians in public hospitals. METHODS: Covering 6 public hospitals in Sichuan (3 tertiary-level hospitals and 3 secondary-level hospitals), 638 questionnaires were obtained from physicians through convenient sampling for data description and analysis. Pearson correlation method was used to analyze the correlation between job satisfaction and work engagement, and multiple linear stepwise regression method was used to analyze work engagement and the influencing factors of each dimension. RESULTS: With regard to job satisfaction, physicians showed high levels of satisfaction in personal safety (3.77±0.87), leadership identification and support (3.59±0.77), and job pressure (3.51±0.81). The mean points of work engagement and each dimension were as follows: total mean points of work engagement (4.02±0.99), dedication (4.21±1.13), absorption (4.19±1.08) and vigor (3.63±1.04). In job satisfaction, salary and benefits, work environment, social recognition, organizational management, leadership identification and support are positively correlated to work engagement and all dimensions. In job satisfaction, 5 dimensions, including social recognition, leadership recognition and support, work achievement, personal safety and organizational management, had a significant influence on work engagement and all dimensions. CONCLUSION: Emphasis on the high-level needs for recognition and self-actualization of doctors, doctor-patient communication, and personal development of doctors may improve doctors' job satisfaction and work engagement.

Fabrication of Supercritical Antisolvent (SAS) Process-Assisted Fisetin-Encapsulated Poly (Vinyl Pyrrolidone) (PVP) Nanocomposites for Improved Anticancer Therapy.

Due to its hydrophobicity, fisetin (FIS) often suffers from several limitations in terms of its applicability during the fabrication of pharmaceutical formulations. To overcome this intrinsic limitation of hydrophobicity, we demonstrate here the generation of poly (vinyl pyrrolidone) (PVP)-encapsulated FIS nanoparticles (FIS-PVP NPs) utilizing a supercritical antisolvent (SAS) method to enhance its aqueous solubility and substantial therapeutic effects. In this context, the effects of various processing and formulation parameters, including the solvent/antisolvent ratio, drug/polymer (FIS/PVP) mass ratio, and solution flow rate, on the eventual particle size as well as on distribution were investigated using a 23 factorial experimental design. Notably, the FIS/PVP mass ratio significantly affected the morphological attributes of the resultant particles. Initially, the designed constructs were characterized systematically using various techniques (e.g., chemical functionalities were examined with Fourier-transform infrared (FTIR) spectroscopy, and physical states were examined with X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) techniques). In addition, drug release as well as cytotoxicity evaluations in vitro indicated that the nanosized polymer-coated particles showed augmented performance efficiency compared to the free drug, which was attributable to the improvement in the dissolution rate of the FIS-PVP NPs due to their small size, facilitating a higher surface area over the raw form of FIS. Our findings show that the designed SAS process-assisted nanoconstructs with augmented bioavailability, have great potential for applications in pharmaceutics.

Comparison of arsenic fractions and health risks in PM2.5 before and after coal-gas replacement.

Coal-Gas replacement project has been implemented to decrease haze pollution in China in recent years. Airborne arsenic (As) mostly originates from coal burning processes. It is noteworthy to compare the distribution of arsenic fraction in PM2.5 before and after coal-gas replacement. Eighty PM2.5 samples were collected in Baoding in December 2016 (coal dominated year) and December 2017 (gas dominated year) at different functional areas including residential area (RA), industrial area (IA), suburb (SB), roadside (ST) and Botanical Garden Park (BG). The fraction, bioavailability and health risk of As in the PM2.5 samples were investigated and compared between these two years. Arsenic was mainly distributed in the non-specifically sorbed fraction (F1) and the residual fraction (F5). However, the proportion of F1 to the total As in 2017 was higher than that in 2016, while the proportion of As in the amorphous and poorly-crystalline hydrous oxides of Fe and Al fraction (F3) in 2017 was lower. The distributions of fraction and bioavailability showed temporal and spatial characteristics. The total concentration and bioavailability of As in SB and IA were significantly higher than those in RA, ST and BG. The BF (Bioavailability Factor) values of As ranged from 0.30 to 0.61. Health risk assessment indicated that the hazard quotient (HQ) and carcinogenic risk (CR) of As in PM2.5 significantly decreased after coal-gas replacement.

A comparative study on arsenic fractions in indoor/outdoor particulate matters: a case in Baoding, China.

The distribution and bioavailability of arsenic (As) in indoor/outdoor total suspended particulates (TSP), inhalable particulate matters (PM10), and fine particulate matters (PM2.5) in Baoding, China were investigated. The average I/O ratios for TSP, PM10, and PM2.5 were 0.52, 0.66, and 0.96, respectively. There was no significant correlation between indoor/outdoor TSP, PM10, and PM2.5. The indoor/outdoor concentrations of As surpassed the limited value of As. I/O ratios of arsenic in TSP, PM10, and PM2.5 were 0.52, 0.58, and 0.55, respectively. The contents of arsenic in different fractions were mainly affected by the total concentrations of arsenic in particulate matters (PM) rather than the particle sizes for TSP and PM10. Arsenic was mainly in non-specifically sorbed fraction (F1) in both indoor and outdoor PM2.5. The evaluated carcinogenic risk (CR) was within the safe level. The bioavailability of As increased with particle size decreasing for both indoor and outdoor PM. The potential bioavailability of As in outdoor particles was higher than that of indoor particles with the same size, especially PM2.5.

Supercritical Fluid-Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes.

Pulmonary delivery of drugs has attracted increasing attention in healthcare, as the lungs are an easily accessible site for noninvasive systemic delivery of drugs. Although pulmonary inhalation of porous microparticles has been shown to sustain drug delivery, there are limited reports on efficient delivery of insulin and inhalation therapy of diabetes based on supercritical carbon dioxide (SC-CO2 ) technology. Herein, this study reports the fabrication of insulin-loaded poly-l-lactide porous microspheres (INS-PLLA PMs) by using the SC-CO2 technology, and their use as an inhalation delivery system potentially for diabetes therapy. Biocompatibility and delivery efficiency of the PLLA PMs in the lungs are investigated. The PLLA PMs show negligible toxicity to lung-derived cells, resulting in no significant reduction in cell viability, as well as levels of various inflammatory mediators such as interleukin (IL)-6, IL-8, and tumor necrosis factor-α, compared with the negative control group. INS-PLLA PMs are further efficiently deposited in the trachea and the bronchi of superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats. Together, the results demonstrate that the INS-PLLA PMs have a strong potential as an effective strategy for inhalation treatment of diabetes.

Overcoming multidrug resistance through inhalable siRNA nanoparticles-decorated porous microparticles based on supercritical fluid technology.

BACKGROUND: In recent times, the co-delivery therapeutics have garnered enormous interest from researchers in the treatment of cancers with multidrug resistance (MDR) due to their efficient delivery of multiple agents, which result in synergistic effects and capable of overcoming all the obstacles of MDR in cancer. However, an efficient delivery platform is required for the conveyance of diverse agents that can successfully devastate MDR in cancer. METHODS: Initially, short-interfering RNA-loaded chitosan (siRNA-CS) nanoparticles were synthesized using the ionic gelation method. Further, the siRNA-CS nanoparticles and doxorubicin hydrochloride (DOX) were co-loaded in poly-L-lactide porous microparticles (PLLA PMs) (nano-embedded porous microparticles, [NEPMs]) by the supercritical anti-solvent (SAS) process. RESULTS AND DISCUSSION: The NEPM formulation exhibited an excellent aerodynamic performance and sustained release of DOX, which displayed higher anticancer efficacy in drug-resistant cells (human small cell lung cancer, H69AR cell line) than those treated with either free DOX and DOX-PLLA PMs due to the siRNA from CS nanoparticles silenced the MDR gene to DOX therapy. CONCLUSION: This eco-friendly process provides a convenient way to fabricate such innovative NEPMs co-loaded with a chemotherapeutic agent and a gene, which can devastate MDR in cancer through the co-delivery system.

Overcoming Multidrug Resistance through the Synergistic Effects of Hierarchical pH-Sensitive, ROS-Generating Nanoreactors.

Recently, multidrug resistance (MDR) has become a major clinical chemotherapeutic burden that robustly diminishes the intracellular drug levels through various mechanisms. To overcome the doxorubicin (Dox) resistance in tumor cells, we designed a hierarchical nanohybrid system possessing copper-substituted mesoporous silica nanoparticles (Cu-MSNs). Further, Dox was conjugated to copper metal in the Cu-MSNs framework through a pH-sensitive coordination link, which is acutely sensitive to the tumor acidic environment (pH 5.0-6.0). In the end, the nanocarrier was coated with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), a P-gp inhibitor-entrenched compact liposome net for obstructing the drug efflux pump. Copper ions in the framework synergize the antitumor activity of Dox by enhancing the intracellular reactive oxygen species (ROS) levels through a Fenton-like reaction-mediated conversion of hydrogen peroxide. Furthermore, intracellularly generated ROS triggered the apoptosis by reducing the cellular as well as mitochondrial membrane integrity in MDR cells, which was confirmed by the mitochondrial membrane potential (MMP) measurement. The advancement of the design and critical improvement of cytotoxic properties through free radical attack demonstrate that the proposed hierarchical design can devastate the MDR for efficient cancer treatment.

[Experimental investigation of nano-TiO2 on combustion and desulfurization Catalysis].

Experiment research of nanometer TiO2 catalytic combustion to CaO desulfurization was studied. Desulfurization effect was measured by the composition analysis of fly ash after combustion and the content of SO2 in flue gas. The effects of analytical grade CaO desulfurization by nanometer TiO2 addition, Ca/S molar ratio, nanometer TiO2 that was prepared at different conditions and combustion temperature were discussed. Desulfurization effects were compared with different coals and Ca-base agents by nanometer TiO2 addition. The reaction products wereanalyzed by X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM) analysis. The combustion desulfurization mechanisms of CaO by nanometer TiO2 addition were discussed. The experiment results show that nanometer TiO2 has good catalytic effect to CaO combustion desulfurization. When nanometer TiO2 was added together with CaO, the optimal addition dosage of nanometer TiO2 is 8%, Ca/S molar ratio is 2 and the combustion temperature is 850 degrees C. The desulfurization efficiency of analytical and industrial grade CaO catalyzed by nanometer TiO2 can achieve to 87.8% and 60.3%, and it increased 13.4% and 29.6% than that without nanometer TiO2. The pore diameter and surface area of different coal ashes with nano-TiO2 addition increase because of the active centers of nano-TiO2 surface which are helpful to the diffusion of SO2 and reaction of SO2 to SO3 and increase the desulphurization efficiency of CaO.

Effect of inhibitors on macroscopical oxidation kinetics of calcium sulfite.

In the presence of inhibitors, the macroscopical oxidation kinetics of calcium sulfite, the main byproduct in wet limestone scrubbing, was studied for the first time by adding different inhibitors and varying pH, concentration of calcium sulfite, oxygen partial pressure, concentration of inhibitors and temperature. The mathematical model about the general oxidation reaction was established, which was controlled by three steps involving dissolution of calcium sulfite, mass transfer of oxygen and chemical reaction in the solution. It was concluded that the general reaction was controlled by mass transfer of oxygen under uncatalyzed conditions, while it was controlled by dissolution of calcium sulfite after adding three kinds of inhibitors. Thus, the theory was provided for investigating the mechanism and oxidation kinetics of sulfite. The beneficial references were also supplied for design of oxidation technics in the wet limestone scrubbing.