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Supercritical Fluid Manufacture
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Ana Aguiar-Ricardo, Eunice Costa
This chapter describes the SCF-based techniques that have been exploited to produce particles fine enough to be appropriately transported to the lungs (i.e. for inhalation product development). The basic concepts and technologies are introduced, with emphasis on formulation issues considering the pulmonary route of administration, for example, control of particle size and distribution, physical stability, solid state, powder characterization, and effects on bioavailability. A thorough understanding of fluid phase equilibria near the critical conditions and their possible influence on the particle formation mechanisms are essential when manipulating the experimental conditions to achieve changes in the solid state and particle properties in a controlled manner.
Supercritical Fluid Extraction as a Sample Preparation Tool in Analytical Toxicology
Published in Steven H. Y. Wong, Iraving Sunshine, Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
Robert J. Maxwell, Janet F. Morrison
The introduction of modifiers in SFE, either for the purpose of increasing analyte solubility in the SF or for facilitating analyte release from matrix binding sites, is generally accomplished in three different ways.5,7,8,59 One approach involves the use of premixed cylinders containing known concentrations of organic modifier(s). These cylinders are commercially available and can be connected directly to the SFE supply pump. The modified fluid is thus delivered directly and continuously to the extraction vessel. This approach is not particularly convenient for method development, nor is it economical because a large number of tanks with a range of modifier types and concentrations are necessary if different applications are performed. Recent studies have also demonstrated that the modifier composition changes as the contents are withdrawn from a cylinder because of shifts in phase equilibria,5,60 which can cause irreproducible results.
Elements of Polymer Science
Published in E. Desmond Goddard, James V. Gruber, Principles of Polymer Science and Technology in Cosmetics and Personal Care, 1999
E. Desmond Goddard, James V. Gruber
Phase equilibria are strongly affected by temperature: raising the temperature of a solution may increase the miscibility of the two components or, less frequently, may result in a decrease of their miscibility. In the first case, as depicted in the phase diagram in Fig. 18). For temperatures below this point, the two components are totally miscible.
Simultaneous affinity maturation and developability enhancement using natural liability-free CDRs
Published in mAbs, 2022
Andre A. R. Teixeira, Sara D’Angelo, M. Frank Erasmus, Camila Leal-Lopes, Fortunato Ferrara, Laura P. Spector, Leslie Naranjo, Esteban Molina, Tamara Max, Ashley DeAguero, Katherine Perea, Shaun Stewart, Rebecca A. Buonpane, Horacio G. Nastri, Andrew R. M. Bradbury
Two different selection strategies were used in this phase: equilibrium selection and kinetic selection (Figure 2aandFigure 2b). 12,33 Equilibrium selection was performed by incubating the scFv-displaying yeast cells with a defined concentration of biotinylated antigen and sorting labeled cells immediately after reaching equilibrium. Incubations are often performed with decreasing antigen concentrations as the selection rounds progress. However, decreasing the antigen concentration cannot be carried out indefinitely because displayed antibodies on the yeast surface will deplete antigen from the solution before reaching equilibrium.34 Avoiding antigen depletion requires the use of large and impractical incubation volumes with small numbers of cells. An alternative to equilibrium selection is kinetic selection: scFv-displaying yeast cells are incubated with the labeled antigen, washed, and incubated with unlabeled antigen to select only clones with stable binding to the antigen (slow off-rate – kd). The far greater excess of unlabeled antigen prevents rebinding of the displaced labeled antigen. After a defined period, cells still bound to the labeled antigen are sorted.
Efficacy of PD-1 blockade therapy and T cell immunity in lung cancer patients
Published in Immunological Medicine, 2020
The cancer immune editing theory consisting of elimination phase, equilibrium phase, and escape phase, describes how tumor cells and immunity interact with each other [1–4]. Because every somatic cell is under immunological surveillance, which recognizes and eradicates the cells producing non-self gene products, the transformed cells presenting mutational products can be recognized by the immune system as non-self and be eradicated in the elimination phase. Sporadic cancer cells that somehow survive immune destruction may enter the equilibrium phase, in which cancer cell proliferation is under control by T cell immunity. T cells preferentially eradicate highly immunogenic clones that likely possess more mutations. Thus, during the equilibrium phase, not only number but also immunogenicity and mutational burden of cancer cells are edited. Conversely, T cell immunity is affected by long-lasting cancer cells, which attenuate its ability to control cancer cells. Immunologically sculpted cancer cells finally enter the escape phase, because of T cell immunity attenuation. Programmed cell death-1 (PD-1), which is known to mediate T cell exhaustion phenomenon of chronic viral infection models, plays a critical role in cancer antigen-mediated T cell suppression [5].
Synthesis, activity evaluation, and pro-apoptotic properties of novel 1,2,4-triazol-3-amine derivatives as potent anti-lung cancer agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Xian-yu Sun, Chun-yan Zhong, Qing-qing Qiu, Zhen-wang Li, Mei-yu Liu, Xin Wang, Cheng-hao Jin
It is well known that the activity of drugs is mainly determined by their structure. One of the main factors is the lipid–water distribution coefficient (LogP value). LogP is an interpretation of the lipid phase and water phase equilibrium ratio of compounds. It can also be employed to determine pharmacological parameters. An increase in the lipid–water distribution coefficient indicates increased solubility of the compound in fat; in contrast, a decrease in this coefficient means increased solubility in water. The solubility of a compound in fatty substances present in the body is known as the hydrophobicity of that compound, whereas the solubility of a compound in water is known as hydrophilicity of that compound. The human body absorbs hydrophilic compounds more easily because of its high water content22. Nonetheless, the cell membrane has a phospholipid bilayer structure that is lipophilic in nature. Thus, if a hydrophilic component of a compound is too large, it cannot enter the cell. Therefore, anti-cancer compounds should be lipophilic to some extent. The extent of drug absorption may also be affected by the magnitude of the LogP value. Hence, an optimal LogP value is necessary to allow a material to easily enter the cell membrane and participate in biological functions. The optimal value for cLogP is approximately 523. Due to the complexity of factors affecting drug activity, a drug needs a suitable cLogP value, but an appropriate cLogP value does not guarantee a good activity. As shown in Table 1, compound 4b and BCTA seem to be two promising structures.