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.     

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.     

Thermal gas effusion from diamond-like carbon films

Good-quality diamond-like carbon films (6 at.% H₂, 2400 kgf/mm² microhardness, 2.7 eV bandgap, higly insulating) have been obtained by the DC glow discharge decomposition of acetylene. Mass spectroscopic thermal effusion measurements were carried out on the films deposited under different deposition conditions. Analyses of hydrogen in conjunction with hydrocarbon effusing species yield information on the microstructure and nature of C---H bonding configurations. It is shown to be a useful analytical tool to study hydrogenated amorphous carbon films of different microstructures varying from polymer-like to diamond-like.     

Performance Analysis of Path Loss Models at 1.8 GHz in an Indoor/Outdoor Environment to Verify Network Capacity and Coverage

Wireless Personal Communications - Cloud is an environment where the resources are outsourced as service to the cloud consumers based on their demand. The cloud providers follows pay as you go...     

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.     

Assessment of fish mercury levels in the upper St. Lawrence River,Canada

The stretch of the St. Lawrence River near Cornwall, Ontario, Canada, between the Moses–Saunders power dam to the eastern outlet of Lake St. Francis in Québec, is currently listed as an Area of Concern (AOC), and has restrictive fish consumption advisories in place, largely due to high mercury levels. This study examined long-term temporal trends of mercury concentrations in northern pike, smallmouth bass, walleye and yellow perch from the St. Lawrence River, including the Cornwall AOC. In addition, differences in fish mercury concentrations among river sections were compared for each species using historical (1975–1979) and recent (2000–2011) data. Statistically significant declines in mercury concentrations were observed in all river sections for yellow perch (~ 40%), as well as in northern pike and walleye in at least one river section. For the river section encompassing the AOC, recent mercury concentrations are 33–59% lower than historical mercury concentrations for all four species. Further, a comparison of recent mercury concentrations between the AOC river section and other Ontario lakes/rivers suggests that AOC mercury values are within the 75th percentile of values for other Ontario water bodies in three of the four species considered. However, current fish mercury values for the AOC river section remain higher than one or more upstream river sections. These results indicate that recovery is still ongoing in this AOC.     

Fabrication and characterization of nanostructured (Sn–Ti)O<Subscript>2</Subscript> pellets and films for liquefied petroleum gas sensing

Present paper reports the synthesis of nanostructured (Sn–Ti)O₂ via physicochemical method, its characterization and performance as liquefied petroleum gas (LPG) sensor. The synthesized material was characterized using XRD that confirmed the formation of (Sn–Ti)O₂ nanocomposite. Minimum crystallite size was found as 7 nm. The material was also investigated through SEM, DSC, FTIR, PL and UV–Vis spectrophotometer. Further, the pellet, thick and thin films were fabricated for the sensing analysis. Pellets (9 mm diameter, 4 mm thickness) of (Sn–Ti)O₂ nanocomposite were made by hydraulic pressing machine by applying uniaxial pressure of 616 MPa, thick films (thickness ~2 µm) were made by screen printing technique and thin films were prepared using a Photo resist spinner unit. Further at room temperature, the pellet and films were exposed to LPG in a gas chamber under controlled conditions at room temperature and variations in resistance with the concentrations of LPG were observed. The maximum value of sensitivity of solid state pellet, thick and thin films based sensors were found 7, 9 and 39 for 5 vol% of LPG, respectively. Sensing characteristics were found to be reproducible, after 6 months of their fabrication, indicating the stability of the sensors.     

Physico‐mechanical properties of nano‐polystyrene‐decorated graphene oxide–epoxy composites

Nano‐polystyrene (nPS)‐decorated graphene oxide (GO) hybrid nanostructures were successfully synthesized using stepwise microemulsion polymerization, and characterized using Fourier transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), field‐emission scanning electron microscopy and transmission electron microscopy. XRD and FTIR spectra revealed the existence of a strong interaction between nPS and GO, which implied that the polymer chains were successfully grafted onto the surface of the GO. The nPS‐decorated GO hybrid nanostructures were compounded with epoxy using a hand lay‐up technique, and the effect of the nPS‐decorated GO on the mechanical, thermal and surface morphological properties of the epoxy matrix was investigated using a universal tensile machine, Izod impact tester, thermogravimetric analysis and contact angle measurements with a goniometer. It was observed that in the epoxy matrix, GO improved the compatibility. © 2017 Society of Chemical Industry