Unsteady axisymmetric stagnation flow on a circular cylinder

Unsteady, axisymmetric stagnation flow about a circular cylinderis examined when the far-field flow is a periodic function oftime with a fixed time average and an oscillatory part of prescribedamplitude and frequency. Solutions are computed for arbitraryvalues of the Reynolds number, quantifying the effects of surfacecurvature, and a frequency parameter based on the period ofthe far-field flow. It is found that solutions remain regularand periodic provided that the far-field amplitude lies belowa critical value. Above this value, solutions terminate in afinite-time singularity. The blow-up time is delayed by increasingthe curvature of the surface. These results are corroboratedby asymptotic predictions valid in the limits of small and largeamplitude and frequency. For large Reynolds number, the problemreduces to the two-dimensional stagnation-point flow againsta plane wall studied by previous authors.     

Polyethylene glycol matrix reduces the rates of photochemical and thermal release of nitric oxide from S-nitroso-N-acetylcysteine

S -nitrosothiols have many biological activities and may act as nitric oxide (NO) carriers and donors, prolonging NO half-life in vivo. In spite of their great potential as therapeutic agents, most S -nitrosothiols are too unstable to isolate. We have shown that the S -nitroso adduct of N -acetylcysteine (SNAC) can be synthesized directly in aqueous and polyethylene glycol (PEG) 400 matrix by using a reactive gaseous (NO/O₂) mixture. Spectral monitoring of the S–N bond cleavage showed that SNAC, synthesized by this method, is relatively stable in nonbuf-fered aqueous solution at 25°C in the dark and that its stability is greatly increased in PEG matrix, resulting in a 28-fold decrease in its initial rate of thermal decomposition. Irradiation with UV light (λ= 333 nm) accelerated the rate of decomposition of SNAC to NO in both matrices, indicating that SNAC may find use for the photogeneration of NO. The quantum yield for SNAC decomposition decreased from 0.65 ± 0.15 in aqueous solution to 0.047 ± 0.005 in PEG 400 matrix. This increased stability in PEG matrix was assigned to a cage effect promoted by the PEG microenvironment that increases the rate of geminated radical pair recombination in the homolytic S–N bond cleavage process. This effect allowed for the storage of SNAC in PEG at −20°C in the dark for more than 10 weeks with negligible decomposition. Such stabilization may represent a viable option for the synthesis, storage and handling of S -nitrosothiol solutions for biomedical applications.     

Interaction of naproxen amphiphilic derivatives with biomembrane models evaluated by differential scanning calorimetry and Langmuir-Blodgett studies

Anti-inflammatory drugs represent a potential new strategy for the treatment of Alzheimer's disease (AD). The ability to cross the blood-brain barrier and to reach brain tissues is a critical point for these drugs and is strictly related to their lipophilicity. Naproxen (NAP) is a non-steroidal anti-inflammatory drug (NSAIDs) under active investigation for AD. To improve its lipophilic character, NAP was conjugated through a diethylamine spacer (EDA) to lipoamino acids (LAA), α-amino acids containing a long alkyl side chain, to obtain the NAP-EDA-LAA10 and NAP-EDA-LAA14 prodrugs. The interaction of NAP and prodrugs with dimyristoylphosphatidylcholine phospholipids, forming either multilamellar vesicles or monolayers (at the air/water interface) and used as biomembrane models, was studied by differential scanning calorimetry and Langmuir-Blodgett techniques. Experimental data showed that NAP conjugation with LAA residues was able to enhance the drug interaction with such biomembrane models.     

Interaction of lipophilic gemcitabine prodrugs with biomembrane models studied by Langmuir-Blodgett technique

The stability and bioavailability of anticancer agents, such as gemcitabine, can be increased by forming prodrugs. Gemcitabine is rapidly deaminated to the inactive metabolite (2('),2(')-difluorodeoxyuridine), thus to improve its stability a series of increasingly lipophilic gemcitabine prodrugs linked through the 4-amino group to valeroyl, lauroyl, and stearoyl acyl chains were synthesized. Studies of monolayer properties are important to improve understanding of biological phenomena involving lipid/gemcitabine or lipid/gemcitabine derivative interactions. The interfacial behavior of monolayers constituted by DMPC plus gemcitabine or lipophilic gemcitabine prodrugs at increasing molar fractions was studied at the air/water interface at temperatures below (10 degrees C) and above (37 degrees C) the lipid phase transition. The effect of the hydrophobic chain length of gemcitabine derivatives on the isotherm of pure DMPC was investigated by surface tension measurement, and the results are reported as molar fractions as a function of mean molecular area per molecule. The results show that the compounds interact with DMPC producing mixed monolayers that are subject to an expansion effect, depending on the prodrug chain length. The results give useful hints of the interaction of these prodrugs with biological membranes and increase knowledge on the incorporation site of such compounds, as a function of their lipophilicity, in a lipid carrier; they may lead to improved liposomal formulation design.     

Calorimetric evaluation of the interaction and absorption of eicosapentaenoic acid by biomembrane models

The interaction of eicosapentaenoic acid, a polyunsaturated fatty acid belonging to the omega-3 class, with biomembrane models represented by multilamellar or unilamellar vesicles made of dimyristoylphosphatidylcholine was monitored by means of differential scanning calorimetry technique. The calorimetric analysis of vesicle prepared in the presence of increasing molar fraction of eicosapentaenoic acid was carried out to show its maximum interaction with biomembrane models evaluating the effects of eicosapentaenoic acid on the biomembrane models thermotropic parameters (transition temperature and enthalpy variation). Furthermore, in order to detect the influence of the presence of hydrophilic or lipophilic media on the entity of the compound absorption by the biomembrane models, kinetic experiments were carried out.The results indicate that eicosapentaenoic acid strongly interacts with the biomembrane models depressing the transition temperature and the enthalpy variation. Eicosapentaenoic acid is absorbed by the biomembrane models and the absorption is affected by the used medium; in fact a bigger absorption happens in the presence of a lipophilic medium.     

Enhancement of gemcitabine affinity for biomembranes by conjugation with squalene: differential scanning calorimetry and Langmuir-Blodgett studies using biomembrane models

Molecular interactions between gemcitabine, alone or conjugated with squalene to form the gem-squalene prodrug, with dimyristoylphosphatidylcholine have been investigated by differential scanning calorimetry and Langmuir film balance techniques to gain information about the interaction of gemcitabine and its prodrug with mammalian cell membranes and to evaluate the potential of liposomes as a delivery system for gemcitabine prodrugs. Phospholipids assembled as multilamellar vesicles or monolayers (at the air water interface) have been used as biomembrane models. Different interactions of gemcitabine, its prodrug, and squalene with the lipid were detected by dispersing the compounds in the MLV and were compared with kinetic experiments carried out to consider the ability of the examined compounds to dissolve in an aqueous medium, to migrate through it, and to be captured by multilamellar vesicles. Their ability to be released from drug-loaded liposomes and be taken up by empty vesicles mimicking biomembranes was also considered. Analysis of the differential scanning calorimetry curves reveals that gemcitabine has very little interaction with multilamellar vesicles whereas the gem-squalene prodrug strongly interacts with multilamellar vesicles. The kinetic experiments suggest that an aqueous medium does not permit the prodrug uptake by the biomembrane models, whereas it is allowed when gem-squalene is gradually released by the liposomes. The molecular area/surface pressure isotherms of the gemcitabine/lipid, gem-squalene/lipid, and pure compound monolayers, in agreement with the calorimetric results, indicate that gem-squalene interacts with the phospholipid monolayer with the squalene moiety in contact with the phospholipid chains and gemcitabine protruding in the aqueous medium.     

广义Bethe树上奇偶马尔可夫链场上的若干极限性质

通过构造两个非负鞅证明了一个强极限定理,然后把它应用到本文所定义的广义Bethe树上的奇偶马尔可夫链场上,从而获得了此马氏链场上的一类强极限定理.     

Calorimetric Evaluation of Glycyrrhetic Acid (GA)- and Stearyl Glycyrrhetinate (SG)-Loaded Solid Lipid Nanoparticle Interactions with a Model Biomembrane

Glycyrrhetic acid (GA) and stearyl glycyrrhetinate (SG) are two interesting compounds from Glycyrrhiza glabra, showing numerous biological properties widely applied in the pharmaceutical and cosmetic fields. Despite these appreciable benefits, their potential therapeutic properties are strongly compromised due to unfavourable physical-chemical features. The strategy exploited in the present work was to develop solid lipid nanoparticles (SLNs) as carrier systems for GA and SG delivery. Both formulations loaded with GA and SG (GA-SLNs and SG-SLNs, respectively) were prepared by the high shear homogenization coupled to ultrasound (HSH-US) method, and we obtained good technological parameters. DSC was used to evaluate their thermotropic behaviour and ability to act as carriers for GA and SG. The study was conducted by means of a biomembrane model (multilamellar vesicles; MLVs) that simulated the interaction of the carriers with the cellular membrane. Unloaded and loaded SLNs were incubated with the biomembranes, and their interactions were evaluated over time through variations in their calorimetric curves. The results of these studies indicated that GA and SG interact differently with MLVs and SLNs; the interactions of SG-SLNs and GA-SLNs with the biomembrane model showed different variations of the MLVs calorimetric curve and suggest the potential use of SLNs as delivery systems for GA.     

Design of Nanotechnological Carriers for Ocular Delivery of Mangiferin: Preformulation Study

(1) Background: Mangiferin (MGN) is a natural compound, showing anti-inflammatory and antioxidant activities for the potential treatment of eye diseases. The poor physicochemical features of MGN (low solubility and high instability) justify its nanoencapsulation into nanostructured lipid carriers (NLC) to improve its ocular bioavailability. (2) Methods: Firstly, MGN-NLC were prepared by the high shear homogenization coupled with the ultrasound (HSH−US) method. Finally, unloaded and MGN-loaded NLC were analyzed in terms of ocular tolerance. (3) Results: MGN-NLC showed good technological parameters suitable for ocular administration (particle size below 200 nm). The ORAC assay was performed to quantify the antioxidant activity of MGN, showing that the antioxidant activity of MGN-NLC (6494 ± 186 μM TE/g) was higher than that of the free compound (3521 ± 271 μM TE/g). This confirmed that the encapsulation of the drug was able to preserve and increase its activity. In ovo studies (HET-CAM) revealed that the formulation can be considered nonirritant. (4) Conclusions: Therefore, NLC systems are a promising approach for the ocular delivery of MGN.