Ultrasonication assisted Layer-by-Layer technology for the preparation of multi-functional anticancer drugs paclitaxel and lapatinib

In this dissertation, ultrasonication assisted Layer-by-Layer (LbL) technology for the preparation of multifunctional poorly water-soluble anticancer drug nanoparticles, paclitaxel and lapatinib, has been developed. Many FDA approved drugs are very low soluble in water; therefore, it is very difficult to load and control their release and targeting efficiently, which greatly confines their application. The development of this method will pave the way for the development and application of those low soluble anticancer drugs. In the first part of this dissertation, the first approach for powerful ultrasonication, the top-down approach (sonicating bulk drug crystals in polyelectrolyte solution), was successfully applied for the preparation of the nanoparticles of paclitaxel. For this approach, a 200 nm diameter was a kind of magic barrier for colloidal particles prepared. This diameter barrier may be related to the nucleation size of the solvent vapor microbubbles. Consequently, agents enhancing bubbling formation (such as NH4HCO3) were applied to decrease paclitaxel colloid particles to 100-120 nm. Those paclitaxel nanoparticles were Layer-by-Layer coated with a 10-20 nm polycation/polyanion shell to provide aqueous colloidal stability and slower particle dissolution. However, a large obstacle of these powerful ultrasonication methods was a necessity of long ca 45 minutes high power ultrasonication which resulted in TiO2contamination from titanium electrode. The small amount of TiO2 contamination from ultrasonication did negatively affect the in vivotesting of this system in mice, and had to be removed before low toxicity of the Layer-by-Layer coated paclitaxel nanoparticles were observed. In the second part of the dissertation, the second approach for sonication, the bottom-up approach (sonicating drug in a water-miscible organic solvent followed by slow water add-in) was successfully applied for the preparation of the nanoparticles of lapatinib and paclitaxel with less powerful sonication. By using polymeric excipients combined with non-ionic and anionic surfactants along with regular sonication, the prepared particle sizes was uniform at around 140-150 nm. Less sonication time (ca 15 minutes) and lower sonication power avoided TiO2 contamination. The amphiphiles attached to the hydrophobic nanoparticles and served as anchors for LbL shell. The inner LbL layers and surfactants minimized the surface free energy, thereby preventing crystal form changes and nanoparticles coalescence, while the outermost layers enhanced colloidal stability. In the third part of the dissertation, LbL shells with PEGylation (using a block copolymer of poly-L-lysine (PLL) and PEG) for lapatinib were developed for enhanced colloidal stability in high molarity PBS buffer. In the above proposed paclitaxel and lapatinib formulation, we obtained 150-200 nm with high drug content of 80-90% due to very thin capsule walls (ca 10 nm). The drug release time from the LbL capsules was found to be between 10 and 20 hours depending on the shell thickness. Washless Layer-by-Layer assembly was used: 1) addition of polycation in the amount that is enough to reverse surface charge of the dispersion to a high positive (+30 mV) value; 2) addition of polyanion in the amount that is enough to reverse surface charge of the dispersion to a high negative (-30 mV) value. No intermediate washing of nanoparticles was done until the shell was complete. The washless method had the advantage of time and energy saving, preservation of the sample structure and no losses of sample. In the last part of the dissertation, we elaborated nanoformulation of two drugs in one nanocapsule locating paclitaxel in the core and lapatinib on the shell periphery. With this formulation, combining in one nanoparticle dual drugs, we reached the drugs\u27 efficiency synergy. In a multidrug-resistant (MDR) ovarian cancer cell line, OVCAR-3, LbL lapatinib/paclitaxel nanocolloids mediated an enhanced cell growth inhibition in comparison with the LbL paclitaxel-only and LbL lapatinib-only treatment, not to say the free one drug treatment

Dendronized fluorosurfactant for highly stable water-in-fluorinated oil emulsions with minimal inter-droplet transfer of small molecules

Fluorosurfactant-stabilized microfluidic droplets are widely used as pico- to nanoliter volume reactors in chemistry and biology. However, current surfactants cannot completely prevent inter-droplet transfer of small organic molecules encapsulated or produced inside the droplets. In addition, the microdroplets typically coalesce at temperatures higher than 80 °C. Therefore, the use of droplet-based platforms for ultrahigh-throughput combination drug screening and polymerase chain reaction (PCR)-based rare mutation detection has been limited. Here, we provide insights into designing surfactants that form robust microdroplets with improved stability and resistance to inter-droplet transfer. We used a panel of dendritic oligo-glycerol-based surfactants to demonstrate that a high degree of inter- and intramolecular hydrogen bonding, as well as the dendritic architecture, contribute to high droplet stability in PCR thermal cycling and minimize inter-droplet transfer of the water-soluble fluorescent dye sodium fluorescein salt and the drug doxycycline

Atomic Sn–enabled high-utilization, large-capacity, and long-life Na anode

Constructing robust nucleation sites with an ultrafine size in a confined environment is essential toward simultaneously achieving superior utilization, high capacity, and long-term durability in Na metal-based energy storage, yet remains largely unexplored. Here, we report a previously unexplored design of spatially confined atomic Sn in hollow carbon spheres for homogeneous nucleation and dendrite-free growth. The designed architecture maximizes Sn utilization, prevents agglomeration, mitigates volume variation, and allows complete alloying-dealloying with high-affinity Sn as persistent nucleation sites, contrary to conventional spatially exposed large-size ones without dealloying. Thus, conformal deposition is achieved, rendering an exceptional capacity of 16 mAh cm−2 in half-cells and long cycling over 7000 hours in symmetric cells. Moreover, the well-known paradox is surmounted, delivering record-high Na utilization (e.g., 85%) and large capacity (e.g., 8 mAh cm−2) while maintaining extraordinary durability over 5000 hours, representing an important breakthrough for stabilizing Na anode

Experimental Research on Sand Sediment Protection on Railway Tracks

The wind-blown sand disaster on the railway has a very important negative influence on the economic development of traffic networks in desert areas. While there are some engineering protection measures for railway sand deposition, they are far from satisfactory in terms of economic efficiency and protection performance. Therefore, it is still of great practical significance to explore novel measures for actively preventing sand deposition on railway tracks in desert areas. In this article, the laws of sand deposition on single and dual tracks were studied with the help of field experiments. On this basis, it can be seen that the deposition of sand on the rear track can be effectively reduced by placing various types of baffles on the track. Field experiments were designed to study the change law of sand deposition ratio in front of the tracks caused by placing baffles of different cross sections. The results show that placing a 45° inclined baffle on the track can reduce the volume of sand deposition by up to 42%. The findings in this paper can provide scientific guidance for the design of new desert railways or novel protective measures for railway sand deposition

Experimental Research on Sand Sediment Protection on Railway Tracks

The wind-blown sand disaster on the railway has a very important negative influence on the economic development of traffic networks in desert areas. While there are some engineering protection measures for railway sand deposition, they are far from satisfactory in terms of economic efficiency and protection performance. Therefore, it is still of great practical significance to explore novel measures for actively preventing sand deposition on railway tracks in desert areas. In this article, the laws of sand deposition on single and dual tracks were studied with the help of field experiments. On this basis, it can be seen that the deposition of sand on the rear track can be effectively reduced by placing various types of baffles on the track. Field experiments were designed to study the change law of sand deposition ratio in front of the tracks caused by placing baffles of different cross sections. The results show that placing a 45° inclined baffle on the track can reduce the volume of sand deposition by up to 42%. The findings in this paper can provide scientific guidance for the design of new desert railways or novel protective measures for railway sand deposition

Quercetin ameliorates pulmonary fibrosis by inhibiting SphK1/S1P signaling

Idiopathic pulmonary fibrosis (IPF) is an agnogenic chronic disorder with high morbidity and low survival rate. Quercetin is a flavonoid found in a variety of herbs with anti-fibrosis function. In this study, bleomycin was employed to induce a pulmonary fibrosis mouse model. The quercetin administration ameliorated bleomycin-induced pulmonary fibrosis, evidenced by the expression level changes of hydroxyproline, fibronectin, α-smooth muscle actin, Collagen I and Collagen III. The similar results were observed in transforming growth factor (TGF)-β-treated human embryonic lung fibroblast (HELF). The bleomycin or TGF-β administration caused the increase of sphingosine-1-phosphate (S1P) level in pulmonary tissue and HELF cells, as well as its activation-required kinase, sphingosine kinase 1 (SphK1), and its degradation enzyme, sphinogosine-1-phosphate lyase (S1PL). However, the increase of S1P, SphK1 and S1PL was attenuated by application of quercetin. In addition, the effect of quercetin on fibrosis was abolished by the ectopic expression of SphK1. The colocalization of SphK1/S1PL and fibroblast specific protein 1 (FSP1) suggested the roles of fibroblasts in pulmonary fibrosis. In summary, we demonstrated that quercetin ameliorated pulmonary fibrosis in vivo and in vitro by inhibiting SphK1/S1P signaling.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Effects of intake air temperature on homogenous charge compression ignition combustion and emissions with gasoline and n-heptane

In a port fuel injection engine, Optimized kinetic process (OKP) technology is implemented to realize HCCI combustion with dual-fuel injection. The effects of intake air temperature on HCCI combustion and emissions are investigated. The results show that dual-fuel control prolongs HCCI combustion duration and improves combustion stability. Dual-fuel HCCI combustion needs lower intake air temperature than gasoline HCCI combustion, which reduces the requirements on heat management system. As intake air temperature decreases, air charge increases and maximum pressure rising rate decreases. When intake air temperature is about 55ºC, HCCI combustion becomes worse and misfire happens. In fixed dual fuel content condition, HC and CO emission decreases as intake air temperature increases. The combination of dual-fuel injection and intake air temperature control can expand operation range of HCCI combustion

CFD–DEM Simulation of Dust Deposition on Solar Panels for Desert Railways

With the greening of the railway energy supply chain, large-scale photovoltaic power stations will be the best choice to integrate with the railways. Understanding the deposition mechanisms and rules of dust grains on photovoltaic panels is of great guiding significance for the operation of photovoltaic (PV) power stations. In this paper, based on computational fluid dynamics (CFD) combined with the discrete element method (DEM), the dynamic dust deposition process on solar panels was simulated, and the flow field around solar panels and the movement of dust particles in the wind were calculated. The simulation results of clay particles (d = 10 mm) and fine sand particles (d = 100 mm) under different wind speeds showed that the clay particles could follow the air flow properly, and their deposition rate was only 4.6%, while the deposition rate of the fine sand particles was up to 32%, which was determined by the inflow wind speed and cohesion parameters. An image of the non-uniform distribution of particles on the panels was given in this paper for the first time. This will provide a basis for a more accurate assessment of the impact of dust accumulation on PV output in real-world environments. These results provide a critical reference for railway photovoltaic power supply development in desertification areas