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91.
Ekaterina S. Dolinina Evgeniya V. Vorobyeva 《Pharmaceutical development and technology》2016,21(5):546-553
The adsorption of the anticoagulant warfarin onto unmodified (UMS) and modified (phenyl (PhMS), methyl (MMS), mercaptopropyl (MPMS)) mesoporous silica materials was studied at pH 1.6 and 7.4 and in the temperature range of 293–325?K. The silica materials were prepared by sol-gel method for further characterization by FTIR spectroscopy, N2 adsorption/desorption method, transmission electron microscopy and zeta potential measurements. The effects of medium pH, temperature and surface modification of mesoporous silica material on their adsorption characteristics (adsorption capacity, thermodynamic parameters of adsorption) relative to anticoagulant warfarin were investigated. It was found that medium acid–base properties strongly affect the adsorption of warfarin due to the pH-dependent structural diversity of the drug and ionization state of the silica surfaces. The adsorption capacity of the silica materials at pH 1.6 decreases in the order: MMS?>?MPMS?>?UMS?>?PhMS. The influence of various non-covalent interactions on the adsorption capacity of the silica materials and energy of the drug-silica interactions is discussed. These results may be useful for the development of a novel delivery system of warfarin. 相似文献
92.
Rudolf Hanel Stefan Thurner Murray Gell-Mann 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(16):6390-6394
Superstatistics describes statistical systems that behave like superpositions of different inverse temperatures β, so that the probability distribution is , where the “kernel” f(β) is nonnegative and normalized [∫f(β)dβ = 1]. We discuss the relation between this distribution and the generalized entropic form . The first three Shannon–Khinchin axioms are assumed to hold. It then turns out that for a given distribution there are two different ways to construct the entropy. One approach uses escort probabilities and the other does not; the question of which to use must be decided empirically. The two approaches are related by a duality. The thermodynamic properties of the system can be quite different for the two approaches. In that connection, we present the transformation laws for the superstatistical distributions under macroscopic state changes. The transformation group is the Euclidean group in one dimension. 相似文献
93.
A Murugan DA Huse S Leibler 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(30):12034-12039
Proofreading mechanisms increase specificity in biochemical reactions by allowing for the dissociation of intermediate complexes. These mechanisms disrupt and reset the reaction to undo errors at the cost of increased time of reaction and free energy expenditure. Here, we draw an analogy between proofreading and microtubule growth which share some of the features described above. Our analogy relates the statistics of growth and shrinkage of microtubules in physical space to the cycling of intermediate complexes in the space of chemical states in proofreading mechanisms. Using this analogy, we find a new kinetic regime of proofreading in which an exponential speed-up of the process can be achieved at the cost of a somewhat larger error rate. This regime is analogous to the transition region between two known growth regimes of microtubules (bounded and unbounded) and is sharply defined in the limit of large proofreading networks. We find that this advantageous regime of speed-error tradeoff might be present in proofreading schemes studied earlier in the charging of tRNA by tRNA synthetases, in RecA filament assembly on ssDNA, and in protein synthesis by ribosomes. 相似文献
94.
Kun-Ta Wu Lang Feng Ruojie Sha Rémi Dreyfus Alexander Y. Grosberg Nadrian C. Seeman Paul M. Chaikin 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(46):18731-18736
DNA is increasingly used as an important tool in programming the self-assembly of micrometer- and nanometer-scale particles. This is largely due to the highly specific thermoreversible interaction of cDNA strands, which, when placed on different particles, have been used to bind precise pairs in aggregates and crystals. However, DNA functionalized particles will only reach their true potential for particle assembly when each particle can address and bind to many different kinds of particles. Indeed, specifying all bonds can force a particular designed structure. In this paper, we present the design rules for multiflavored particles and show that a single particle, DNA functionalized with many different “flavors,” can recognize and bind specifically to many different partners. We investigate the cost of increasing the number of flavors in terms of the reduction in binding energy and melting temperature. We find that a single 2-μm colloidal particle can bind to 40 different types of particles in an easily accessible time and temperature regime. The practical limit of ∼100 is set by entropic costs for particles to align complementary pairs and, surprisingly, by the limited number of distinct “useful” DNA sequences that prohibit subunits with nonspecific binding. For our 11 base “sticky ends,” the limit is 73 distinct sequences with no unwanted overlaps of 5 bp or more. As an example of phenomena enabled by polygamous particles, we demonstrate a three-particle system that forms a fluid of isolated clusters when cooled slowly and an elastic gel network when quenched. 相似文献
95.
Yixuan Dong Leanna Hengst Deval Patel Robert Hunt Haiou Qu Stephanie Choi Muhammad Ashraf Celia N. Cruz Xiaoming Xu 《Journal of pharmaceutical sciences》2019,108(6):2002-2011
Pharmaceutical emulsions contain multiple components, such as micellar, aqueous, and oil phases, leading to complex drug transfer and equilibrium phenomena. These complex components present challenges for the bioequivalence assessment of the drug products. The objective of the study was to develop a method that can probe the underlying mechanism and process of drug distribution. The concept of drug partitioning into biphasic systems was used to simplify the complex transfer phenomenon. A kinetic method was developed taking into account the biphasic diffusion. Using this approach, both the rate (kinetics) and the extent (equilibrium) of distribution can be determined. For method development purpose, 3 model compounds (triamcinolone acetonide, difluprednate, and cyclosporine), with expected partition coefficient values ranging from 2 to 6, were tested using the kinetic method and the traditional shake-flask method. The values obtained by the 2 methods for all compounds correlated well (r2 = 0.825). Various organic and aqueous solvents which are commonly encountered in formulations were also tested to determine the impact of phase composition on drug distribution. The kinetic method was found to offer more flexibility in terms of solvent composition and can lead to better understanding for drug distribution and potential drug release in complex biphasic systems. 相似文献
96.
97.
98.
Li L Dantzer JJ Nowacki J O'Callaghan BJ Meroueh SO 《Chemical biology & drug design》2008,71(6):529-532
Compounds designed solely based on structure often do not result in any improvement of the binding affinity because of entropy-enthalpy compensation. Thermodynamic data along with structure provide an opportunity to gain a deeper understanding of this effect and aid in the refinement of scoring functions used in computational drug design. Here, we scoured the literature and constructed the most comprehensive hand-curated calorimetry dataset to date. It contains thermodynamic and structural data for more than 400 receptor-ligand complexes. The dataset can be accessed through a web interface at http://www.pdbcal.org. The thermodynamic data consists of free energy, enthalpy, entropy and heat capacity as measured by isothermal titration calorimetry (ITC). The dataset also contains the experimental conditions that were used to carry out the ITC experiments. The chemical structures of the ligands are also provided. Analysis of the data confirms the existence of enthalpy-entropy compensation effect for the first time using strictly ITC data. 相似文献
99.
Bradley D. Anderson 《Journal of pharmaceutical sciences》2018,107(1):24-33
The evolving challenges associated with the development of poorly soluble drug molecules have been met with major advances in drug solubilization. In particular, amorphous solid dispersion technology is becoming an increasingly important option to enhance oral bioavailability by creating prolonged drug supersaturation to maximize the driving force for intestinal absorption. A primary concern in the development of amorphous solid dispersions is their physical stability, leading to increasing interest in predictive methodologies to assess the propensity for drug crystallization under various storage conditions. For most drug-excipient combinations of pharmaceutical interest, hydrogen bonding is an important factor in determining miscibility, supersaturation potential, and the influence of water uptake during storage and after administration. The vast majority of publications to date have utilized mathematical models based on regular solution theory such as Flory-Huggins theory to predict drug-polymer miscibility, despite the fact that they were never intended to be applied to hydrogen-bonded systems. In this commentary article, regular solution theory is applied to simple hydrogen-bonded alcohol-alkane solutions to explore trends in the Flory-Huggins χ interaction parameter and possible pitfalls in its interpretation. More recent models that explicitly allow for specific interactions merit greater attention. 相似文献
100.
Jorjadze I Pontani LL Newhall KA Brujic J 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(11):4286-4291
It remains an open question whether statistical mechanics approaches apply to random packings of athermal particles. Although a jamming phase diagram has recently been proposed for hard spheres with varying friction, here we use a frictionless emulsion system in the presence of depletion forces to sample the available phase space of packing configurations. Using confocal microscopy, we access their packing microstructure and test the theoretical assumptions. As a function of attraction, our packing protocol under gravity leads to well-defined jammed structures in which global density initially increases above random close packing and subsequently decreases monotonically. Microscopically, the fluctuations in parameters describing each particle, such as the coordination number, number of neighbors, and local packing fraction, are for all attractions in excellent agreement with a local stochastic model, indicating that long-range correlations are not important. Furthermore, the distributions of local cell volumes can be collapsed onto a universal curve using the predicted k-gamma distribution, in which the shape parameter k is fixed by the polydispersity while the effect of attraction is captured by rescaling the average cell volume. Within the Edwards statistical mechanics framework, this result measures the decrease in compactivity with global density, which represents a direct experimental test of a jamming phase diagram in athermal systems. The success of these theoretical tools in describing yet another class of materials gives support to the much-debated statistical physics of jammed granular matter. 相似文献