In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

Conducting composites of polythiophene and polyfuran with acetylene black

Conducting composites of polythiophene (PTP) and polyfuran (PF) with acetylene black (AB) were prepared via chemical oxidative polymerization of thiophene and furan in a suspension of AB in CHCl₃ at room temperature using anhydrous FeCl₃ as the oxidant. Formation of PTP and PF and their subsequent incorporation in PTP–AB and PF–AB composite systems were confirmed by FTIR analysis. Scanning electron microscope analysis showed the presence of compact clusters of particles in both composites. Transmission electron micrographs of PTP–AB and PF–AB composites showed formation of globular polymer encapsulated AB particles with average diameters of the order of ～100 nm in both systems. Thermogravimetric analysis revealed that the overall thermal stability varied in the order: AB > PTP–AB > PTP and AB > PF–AB > PF. DC conductivity values for the PTP–AB and PF–AB composites were of the order of 10^?2 and 10^?3 S cm^?1, respectively. Copyright © 2004 Society of Chemical Industry     

Conducting composites of poly(N‐vinylcarbazole), polypyrrole,and polyaniline with 13X‐zeolite

N‐vinylcarbazole (NVC) was polymerized by 13X zeolite alone in melt (65°C) or in toluene (110°C) and a poly(N‐vinylcarbazole) (PNVC)‐13X composite was isolated. Composites of polypyrrole (PPY) and polyaniline(PANI) with 13X zeolite were prepared via polymerization of the respective monomers in the presence of dispersion of 13X zeolite in water (CuCl₂ oxidant) and in CHCl₃ (FeCl₃ oxidant) at an ambient temperature. The composites were characterized by Fourier transform infrared analyses. Scanning electron microscopic analyses of various composites indicated the formation of lumpy aggregates of irregular sizes distinct from the morphology of unmodified 13X zeolite. X‐ray diffraction analysis revealed some typical differences between the various composites, depending upon the nature of the polymer incorporated. Thermogravimetric analyses revealed the stability order as: 13X‐zeolite > polymer‐13X‐zeolite > polymer. PNVC‐13X composite was essentially a nonconductor, while PPY‐13X and PANI‐13X composites showed direct current conductivity in the order of 10^?4 S/cm in either system. However, the conductivity of PNVC‐ 13X composite could be improved to 10^?5 and 10^?6 S/cm by loading PPY and PANI, respectively. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 913–921, 2006     

Differential proteomics of human seminal plasma: A potential target for searching male infertility marker proteins

The clinical fertility tests, available in the market, fail to define the exact cause of male infertility in almost half of the cases and point toward a crucial need of developing better ways of infertility investigations. The protein biomarkers may help us toward better understanding of unknown cases of male infertility that, in turn, can guide us to find better therapeutic solutions. Many clinical attempts have been made to identify biomarkers of male infertility in sperm proteome but only few studies have targeted seminal plasma. Human seminal plasma is a rich source of proteins that are essentially required for development of sperm and successful fertilization. This viewpoint article highlights the importance of human seminal plasma proteome in reproductive physiology and suggests that differential proteomics integrated with functional analysis may help us in searching potential biomarkers of male infertility.     

Cover Feature: Superior Proton-Transfer Catalytic Promiscuity of Cytochrome c in Self-Organized Media (7/2021)

Evolutionarily elderly proteins commonly feature greater catalytic promiscuity. Cytochrome c is among the first set of proteins in evolution to have known prospects in electron transport and peroxidative properties. Here, we report that cyt c is also a proficient proton-transfer catalyst and enhances the Kemp elimination (KE; model reaction to show proton transfer catalytic property) by ∼750-fold on self-organized systems like micelles and vesicles. The self-organized systems mimic the mitochondrial environment in vitro for cyt c. Using an array of biophysical and biochemical mutational assays, both acid–base and redox mechanistic pathways have been explored. The histidine moiety close to hemin group (His18) is mainly responsible for proton abstraction to promote the concerted E2 pathway for KE catalysis when cyt c is in its oxidized form; this has also been confirmed by a H18A mutant of cyt c. However, the redox pathway is predominant under reducing conditions in the presence of dithiothreitol over the pH range 6–7.4. Interestingly, we found almost 750-fold enhanced KE catalysis by cyt c compared to aqueous buffer. Overall, in addition to providing mechanistic insights, the data reveal an unprecedented catalytic property of cyt c that could be of high importance in an evolutionary perspective considering its role in delineating the phylogenic tree and also towards generating programmable designer biocatalysts.     

Evaluating the role of composition and local structure on alkali out-diffusion in glasses for thin-film solar cells

The presence of alkali ions has reportedly improved the performance of CIGS/CZTS–based thin-film solar cells. The out-diffusion of the alkali ion, in particular, Na, from the glass substrate offers a facile scalable route of supplying the alkali ions during the growth of the absorber layer. In this work, we demonstrate the diffusion of different alkali ions (Li/Na/K) from composition tuned glasses with intentionally incorporated excess alkali ions into a thin Mo film, typically used as a bottom electrode in solar cells. We also evaluate the physical, mechanical, and thermal properties of the glasses for suitability as a substrate in thin-film deposition. The out-diffusion of alkali ions to the overlayer is found to be critically influenced by the composition and the local structure of the glasses. The Na ions exhibit the highest extent of diffusion among the alkali ions present in glass substrates, while that for the K-ions is the lowest. For the glasses with mixed alkali ions, the presence of Li facilitated the out-diffusion of Na, whereas K ions appear to inhibit the same. Differently with the existing reports, we show that the activation energy and the presence of Ca ions as additional modifiers play a crucial role in the transport mechanism of the ions. In addition, the synthesized glasses exhibit hardness of the order 5-7 GPa, density ~2.55 g cm^-3. The glass transition temperature lies between 535 and 580°C and the coefficient of thermal expansion 8.5-10 ppm/K, which is highly suitable for use as substrates in thin-film solar cells.     

A mathematical model for wave propagation in a composite solid matrix containing two immiscible fluids

Constitutive relations and field equations have been extended for a porous medium composed of two solids and containing two chemically non-reactive immiscible fluids. By generalizing the closure relation of porosity change and employing this into the mass balance equations, the stress–strain relations have been developed. The idea of generalized compressibility tests is invoked to find the value of dimensionless parameters appearing in the closure relation of porosity change. By generalizing momentum balance equations of Lo et al. (Water Resour Res 41:1–20, 2005), the propagation of dilatational and rotational waves is explored. It is found that four dilatational and two rotational waves exist in the porous medium. In contrast to Biot’s theory, the presence of the second fluid and second solid in the porous medium gives rise to additional P- and S-waves. Variation of phase speeds and corresponding attenuation coefficients of existing waves versus frequency, saturation of the fluid phases and solid fraction are computed numerically and depicted graphically.     

Comparing and aggregating partially resolved trees

Partially-resolved-that is, non-binary-trees arise frequently in the analysis of species evolution. Non-binary nodes, also called multifurcations, must be treated carefully, since they can be interpreted as reflecting either lack of information or actual evolutionary history. While several distance measures exist for comparing trees, none of them deal explicitly with this dichotomy. Here we introduce two kinds of distance measures between rooted and unrooted partially-resolved phylogenetic trees over the same set of species; the measures address multifurcations directly. For rooted trees, the measures are based on the topologies the input trees induce on triplets; that is, on three-element subsets of the set of species. For unrooted trees, the measures are based on quartets (four-element subsets). The first class of measures are parametric distances, where there is a parameter that weighs the difference between an unresolved triplet/quartet topology and a resolved one. The second class of measures are based on the Hausdorff distance, where each tree is viewed as a set of all possible ways in which the tree can be refined to eliminate unresolved nodes. We give efficient algorithms for computing parametric distances and give conditions under which Hausdorff distances can be calculated approximately in polynomial time. Additionally, we (i) derive the expected value of the parametric distance between two random trees, (ii) characterize the conditions under which parametric distances are near-metrics or metrics, (iii) study the computational and algorithmic properties of consensus tree methods based on the measures, and (iv) analyze the interrelationships among Hausdorff and parametric distances.