Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and β-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.     

Diameter preserving linear maps and isometries

We study linear bijections of C(X) which preserve the diameter of the range, that is, the seminorm r(f)=sup{|f(x)-f(y)| : x, y ? X}\varrho (f)={\rm sup}\{|f(x)-f(y)| : x, y\in X\}.     

How to Approximate the Heat Equation with Neumann Boundary Conditions by Nonlocal Diffusion Problems

We present a model for nonlocal diffusion with Neumann boundary conditions in a bounded smooth domain prescribing the flux through the boundary. We study the limit of this family of nonlocal diffusion operators when a rescaling parameter related to the kernel of the nonlocal operator goes to zero. We prove that the solutions of this family of problems converge to a solution of the heat equation with Neumann boundary conditions.     

Ultrastructural Damages to H1N1 Influenza Virus Caused by Vapor Essential Oils

Influenza viruses are transmitted from human to human via airborne droplets and can be transferred through contaminated environmental surfaces. Some works have demonstrated the efficacy of essential oils (EOs) as antimicrobial and antiviral agents, but most of them examined the liquid phases, which are generally toxic for oral applications. In our study, we describe the antiviral activity of Citrus bergamia, Melaleuca alternifolia, Illicium verum and Eucalyptus globulus vapor EOs against influenza virus type A. In the vapor phase, C. bergamia and M. alternifolia strongly reduced viral cytopathic effect without exerting any cytotoxicity. The E. globulus vapor EO reduced viral infection by 78% with no cytotoxicity, while I. verum was not effective. Furthermore, we characterized the EOs and their vapor phase by the head-space gas chromatography–mass spectrometry technique, observing that the major component found in each liquid EO is the same one of the corresponding vapor phases, with the exception of M. alternifolia. To deepen the mechanism of action, the morphological integrity of virus particles was checked by negative staining transmission electron microscopy, showing that they interfere with the lipid bilayer of the viral envelope, leading to the decomposition of membranes. We speculated that the most abundant components of the vapor EOs might directly interfere with influenza virus envelope structures or mask viral structures important for early steps of viral infection.     

Conductivity of lithium perfluorononanoate in water-poly(vinyl pyrrolidone) solutions

Conductivity measurements, focused on the counterion binding of lithium perfluorononanoate (LiPFN) micelles in pure water and in the presence of poly(vinyl pyrrolidone) (PVP), have been carried out. An abrupt decrease of the conductance of the LiPFN in pure water, due to the self aggregation of anions and to dynamic linkage of cations on the micellar surface, has been found. Analysis of the conductometric data indicates that about 50% of the stoichiometric concentration of Li⁺ interacts with the head groups of the perfluorinated anions involved in micellar assembly. Conductometric data of LiPFN-water-PVP systems reveals a favorable influence of the PVP on the micellization process modulated by the concentration and by the molecular weight of the polymer. Analysis of these data shows that in presence of PVP the degree of binding of lithium ion to the micellar assemblies linked to the polymer is smaller than in pure water. By increasing the amount of surfactant in solution up to the concentration where the polymer becomes saturated by LiPFN micelles, the binding of lithium ion in the system becomes slightly greater than that observed in LiPFN-water system. This finding can be interpreted in terms of additional binding of lithium ion to the polymer chains. Conductivity measurements carried out on LiClO₄ and KClO₄ in water + PVP support this interpretation.     

Bigels: A unique class of materials for drug delivery applications

Bigels, combination of organogel and hydrogel, are unique solid-like formulations with improved properties for food, cosmetics, and pharmaceutical applications. Bigel possesses merits of both phases, aqueous and oily, and displays better properties than either of the single gel. The uniqueness of bigels comes from their ability to deliver both hydrophilic and lipophilic active agents, enrichment of hydration of stratum corneum, easily spreadable, and so on. The main objective of this review article is to provide a thorough insight into the classification of bigels on the basis of synthesis method and morphology and also to demonstrate the detailed analysis of bigel formulations by considering different characterization techniques. Moreover, a special focus is given on the applications of bigels as drug delivery vehicles by transdermal route.     

Nonaqueous capillary electrophoresis method for the analysis of tamoxifen, imipramine and their main metabolites in urine

The viability of nonaqueous capillary electrophoresis (NACE) was investigated for the simultaneous determination of tamoxifen, imipramine and their main metabolites (4-hydroxytamoxifen and desipramine, respectively). Baseline separation of the studied solutes was obtained on a 57 cm × 75 μm capillary using a nonaqueous solution composed of 17 mM ammonium acetate and 1.25% acetic acid in 80:20 (v:v) methanol-acetonitrile, temperature and voltage 22 °C and 15 kV, respectively, and hydrodynamic injection. Paroxetine was used as internal standard. Different aspects including linearity, accuracy, ruggedness and precision was studied. Detection limits between 9.0 and 15.0 μg L⁻¹ were obtained for all the studied compounds. The developed method is simple, rapid and sensitive and has been used to determine tamoxifen, imipramine and their metabolites at clinically relevant levels in human urine. Before NACE determination, a solid phase extraction (SPE) procedure with a C₁₈ cartridge was necessary. Real determination of these analytes in three females urines were done.     

The role of Rh on a substituted Al Anderson heteropolymolybdate: Thermal and hydrotreating catalytic behavior

The influence of Rh heteroatom on the molybdenum reducibility in the Anderson-type heteropolyoxomolybdate structure of formula (NH₄)₃[RhMo₆O₂₄H₆]·7H₂O was investigated by means of TPR technique. With comparative purposes, the thermal behavior in non-reducing conditions was also carried out by means of TGA-DTA studies. The study was performed by XRD, SEM, EDAX and FTIR-Raman techniques. Results were related to those preliminary measurements over other XMo₆ Anderson phases. Likewise, Rh(III)-Al(III) formal replacement in the RhMo₆ structural arrangement was proved. The formation of a solid solution in a limited range of composition (up to 0.25 Rh) was established in order to explore the catalytic performance of γ-Al₂O₃ supported planar heteropolyoxomolybdate, aiming at optimizing the noble metal content in the catalytic system. Preliminary measurements of RhMo₆/γ-Al₂O₃ and (Rh, Al)Mo₆/γ-Al₂O₃ activity for HDS and HYD processes were also performed. These results were compared to those obtained for CoMo₆/γ-Al₂O₃ system in similar operating conditions and other conventional catalytic systems. The potentiality and scope of RhMo₆ catalytic system for the HDS and HYD processes were analyzed.     

Covering point sets with two disjoint disks or squares

We study the following problem: Given a set of red points and a set of blue points on the plane, find two unit disks C_R and C_B with disjoint interiors such that the number of red points covered by C_R plus the number of blue points covered by C_B is maximized. We give an algorithm to solve this problem in O(n^8/3log²n) time, where n denotes the total number of points. We also show that the analogous problem of finding two axis-aligned unit squares S_R and S_B instead of unit disks can be solved in O(nlogn) time, which is optimal. If we do not restrict ourselves to axis-aligned squares, but require that both squares have a common orientation, we give a solution using O(n³logn) time.