Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

Paclitaxel is a diterpenoid isolated from Taxus brevifolia. It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor® EL (BASF, Ludwigshafen, Germany), which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was formulated as a nanosuspension by high-pressure homogenization. The nanosuspension was lyophilized to obtain the dry paclitaxel nanoparticles (average size, 214.4 ± 15.03 nm), which enhanced both the physical and chemical stability of paclitaxel nanoparticles. Paclitaxel dissolution was also enhanced by the nanosuspension. Differential scanning calorimetry showed that the crystallinity of paclitaxel was preserved during the high-pressure homogenization process. The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection. In rat plasma, paclitaxel nanosuspension exhibited a significantly (P < 0.01) reduced area under the concentration curve (AUC)0–∞ (20.343 ± 9.119 μg · h · mL−1 vs 5.196 ± 1.426 μg · h · mL−1), greater clearance (2.050 ± 0.616 L · kg−1 · h−1 vs 0.556 ± 0.190 L · kg−1 · h−1), and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours) compared with the paclitaxel solution. In contrast, the paclitaxel nanosuspension resulted in a significantly greater AUC0–∞ in liver, lung, and spleen (all P < 0.01), but not in heart or kidney

Bis[2-(benzyl­imino­meth­yl)pyrrol-1-ido-κ2 N,N′]bis­(dimethyl­amido-κN)titanium(IV)

The mononuclear title complex, [Ti(C2H6N)2(C12H11N2)2], was synthesized by the reaction of 1-phenyl-N-[(pyrrol-2-yl)methyl­idene]methanamine with Ti(NMe2)4. The TiIV atom is coordinated in a distorted octa­hedral geometry by four N atoms from two derivatized methanamine ligands and two N atoms from two dimethyl­amide ions. The dihedral angles between the pyrrole and phenyl rings in the bidentate ligands are 62.36 (9) and 78.32 (8)°. In the crystal, a weak π–π stacking inter­action [centroid–centroid distance = 3.864 (2) Å] involving centrosymmetrically related mol­ecules is observed

Mechanism and Prevention Technologies of Reservoir Gas Disaster in Abandoned Oil Well of Coal Mine

AbstractThe reservoir gas disaster has distinct characteristics and is a key factor that threatens the safe and green mining of coal mines in the costorage area of coal and petroleum resources. In order to solve the problem of prevention and control of reservoir gas disasters in coal mines, the characteristics of oil-bed gas disasters in abandoned oil wells in coal mines were analyzed, and the oil-bed gas disaster mechanism of abandoned oil wells without isolation coal pillars was revealed to study the scope of gas disasters around oil wells under the influence of production. The research shows that: (1) abandoned oil well reservoir gas disasters have the characteristics of high gas pressure, high concentration, large lateral influence area, wide vertical sweep range, and frequent disasters, which seriously threaten the safety and green mining of coal mines; (2) divide the reservoir gas disaster of abandoned oil wells into the high-pressure gas disaster in the well and the disaster in the surrounding oil-bed gas enrichment area; (3) according to the numerical simulation results that the maximum damage depth of the coal seam mining floor is 38.6 m and the seepage height of high-pressure oil-bed gas is 40 m, the safety factor k is introduced, and the reservoir gas sweeping range of the abandoned oil well is determined to be 95.4 m below the coal seam to the surface; (4) the comprehensive prevention and control technical scheme of oil-bed gas for controlling high-pressure oil-bed gas in wells by ground plugging and downhole injection and injection of diluent to control enriched areas was proposed, which successfully solved the problem of safe and efficient exploitation of Shuangma coal mine in Ningdong coalfield by abandoned oil wells. The research results provide effective solutions for the realization of green mining in many coal mines in the costorage area of coal and oil resources in China and have important application value for the prevention and control of dynamic disasters in the costorage area of resources

Intranasal Delivery of Cationic PLGA Nano/Microparticles- Loaded FMDV DNA Vaccine Encoding IL-6 Elicited Protective Immunity against FMDV Challenge

Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV) and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide)) nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing mucosal and systemic immune responses in animals. Three eukaryotic expression plasmids with or without bovine IL-6 gene (pc-P12A3C, pc-IL2AP12A3C and pc-P12AIL3C) were generated. The two latter plasmids were designed with the IL-6 gene located either before or between the P12A and 3C genes, respectively, as a means of determining if the location of the IL-6 gene affected capsid assembly and the subsequent immune response. Guinea pigs and rats were intranasally vaccinated with the respective chitosan-coated PLGA nano/microparticles-loaded FMDV DNA vaccine formulations. Animals immunized with pc-P12AIL3C (followed by animals vaccinated with pc-P12A3C and pc-IL2AP12A3C) developed the highest levels of antigen-specific serum IgG and IgA antibody responses and the highest levels of sIgA (secretory IgA) present in mucosal tissues. However, the highest levels of neutralizing antibodies were generated in pc-IL2AP12A3C-immunized animals (followed by pc-P12AIL3C- and then in pc-P12A3C-immunized animals). pc-IL2AP12A3C-immunized animals also developed stronger cell mediated immune responses (followed by pc-P12AIL3C- and pc-P12A3C-immunized animals) as evidenced by antigen-specific T-cell proliferation and expression levels of IFN-γ by both CD4+ and CD8+ splenic T cells. The percentage of animals protected against FMDV challenge following immunizations with pc-IL2AP12A3C, pc-P12AIL3C or pc-P12A3C were 3/5, 1/5 and 0/5, respectively. These data suggested that intranasal delivery of cationic PLGA nano/microparticles loaded with various FMDV DNA vaccine formulations encoding IL-6 as a molecular adjuvant enhanced protective immunity against FMDV, particularly pc-IL2AP12A3C with IL-6 gene located before P12A3C gene

Evolutionary Analysis of Structural Protein Gene VP1 of Foot-and-Mouth Disease Virus Serotype Asia 1

Foot-and-mouth disease virus (FMDV) serotype Asia 1 was mostly endemic in Asia and then was responsible for economically important viral disease of cloven-hoofed animals, but the study on its selection and evolutionary process is comparatively rare. In this study, we characterized 377 isolates from Asia collected up until 2012, including four vaccine strains. Maximum likelihood analysis suggested that the strains circulating in Asia were classified into 8 different groups (groups I–VIII) or were unclassified (viruses collected before 2000). On the basis of divergence time analyses, we infer that the TMRCA of Asia 1 virus existed approximately 86.29 years ago. The result suggested that the virus had a high mutation rate (5.745 × 10−3 substitutions/site/year) in comparison to the other serotypes of FMDV VP1 gene. Furthermore, the structural protein VP1 was under lower selection pressure and the positive selection occurred at many sites, and four codons (positions 141, 146, 151, and 169) were located in known critical antigenic residues. The remaining sites were not located in known functional regions and were moderately conserved, and the reason for supporting all sites under positive selection remains to be elucidated because the power of these analyses was largely unknown

Determining Soil Available Water Capacity and Reasonable Irrigation Volume in Dryland Pasture

Among the methods used to describe soil-available water in terms of yield, field water capacity and permanent wilting coefficient were considered as the upper and lower boundaries, respectively, for normal plant growth. This study investigated the soil properties and groundwater resources of the Hailiutu pasture in Inner Mongolia, China. Soil water characteristics and hydraulic conductivity function curves of the pasture soil were measured based on filter paper method. Experimental results showed that air-entry and residual value were determined to be 34.6% and 13.1%, corresponding to the field water capacity and permanent wilting coefficient, respectively, and the available water capacity was 218.0 mm. The downward velocity of the soil wetting front in the silt is 3.0 mm/h. Site investigation revealed that the pasture was a natural capillary barrier, and its critical suction could optimize the upper boundary of irrigation. Considering the limited underground water resources, shallow water level, and the transpiration of Caragana Korshinskii in the pasture, an available drip irrigation method was designed. The spacing between drip irrigation pipes is 60 cm, the spacing between drip holes is 60 cm, the drip irrigation volume per hole is 475.2~838.8 mL/d, the drip irrigation time is 110~200 min at each night. Each hectare pasture exhausts 13.5~22.5 m3 water each day. Field tests showed that the proposed method is feasible and can be used for irrigation in dryland pastures

A Brief Interpretation of CCAC Guide on Humane Endpoints of Animals: 2022 Edition

The 2022 Canadian Council On Animal Care (CCAC) guidelines: Identification of Scientific Endpoints, Human Intervention Points, and Cumulative Endpoints (CCAC Guide) supplements existing laboratory animal humane endpoint theory according to the latest available literature. This article summarized the main content of the 2022 CCAC Guide, and elaborated and analyzed the determination, implementation and supervision of the scientific endpoints, humane intervention points, and cumulative endpoints of animal experiments, in order to provide useful reference and information