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.     

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.     

Performance assessment of hybrid composite friction materials based on flyash–rock fibre combination

Friction composites based on several combinations of flyash and inorganic mineral rock fibres such as lapinus™ fibre were fabricated, characterised and tribo-evaluated. The tribo-performance in terms of their friction-fade and friction-recovery behaviour has been rigorously evaluated while synchronously taking into account of the in situ braking induced temperature rise in the disc at the braking interface on a Krauss friction testing machine following pulse velocity wave (PVW) 3212 norms as per the Economic Commission for Europe (ECE) regulations. The fade behaviour has been observed to be highly dependent on the combination of flyash–lapinus fibre e.g. fade remained maximum (45%) in the composite with the highest amount of lapinus fibre content and lowest amount of flyash whereas the frictional fluctuations in terms of μ_max − μ_min has been observed to be higher in case of low flyash–high lapinus fibre combination. The recovery response seemed unaffected by the disparity of ingredients and remained consistently stable within the range of 112 ± 2%. The analysis of friction and wear performance has revealed that flyash along with lapinus fibre provide thermo-mechanical stability and overall mechanical integrity to the system causing reduction in friction-fade whereas wear was found to be more recovery-controlled and less fade controlled. Worn surface morphology investigation using SEM has been carried out which has revealed that the interplay of flyash–lapinus combination and topographical attributes vis-a-vis dynamics of contact patches (formation–destruction) largely influence the friction and wear performance of such composites.     

Probiotic properties of folate producing Streptococcus thermophilus strains

This study aimed at assessing the probiotic potential of two high folate producing Streptococcus thermophilus strains (RD102 and RD104) isolated from Indian fermented milk products by both in vitro and in vivo tests. These strains were able to survive at pH 2.5 and 2% bile with a good bile salt hydrolase activity, cell surface hydrophobicity and sensitivity to most of the clinically important antibiotics. On evaluation for gastrointestinal transit tolerance these showed a viable count of 5 log cfu mL^?1 and 7 log cfu mL^?1, respectively in simulated gastrointestinal juice of pH 2.0 and 2% bile. During the in vivo feeding trial in mice the strains showed a viable count of about 7 log cfu g^?1 faeces and 6 log cfu g^?1 of large intestine, respectively. These strains were hence observed to possess favorable strain specific probiotic properties and have the potential to be a source of novel probiotics.     

An ab initio study of ZrB2–SiC interface strength as a function of temperature: Correlating phononic and electronic thermal contributions

This work focuses on understanding correlations between thermal conduction and mechanical strength in a model high temperature material interface. Analyses examine single crystal ZrB₂, single crystal SiC, and a 〈0 0 0 1〉–〈1 1 1〉 ZrB₂–SiC interface using a framework based on Car Parrinello molecular dynamics (CPMD) ab initio simulation method from 500 K to 2500 K. Analyses indicate that the strength reduction with increase in temperature is strongly correlated to phonon and electron thermal diffusivity change. With increase in temperature, phonon thermal diffusivity increases in the case of ZrB₂ and reduces in the cases of SiC as well as the interface. Electron contribution to thermal diffusivity increases with temperature increase in the case of interface. Examination of change in thermal properties at different mechanical strain levels reveals that the mechanisms of strength and thermal property change with increase in temperature may be similar to the mechanisms responsible for property change with change in applied strain.     

Effects of manufacturing tolerances on the electrical performance of suspended and inverted microstrip lines

Effects of manufacturing tolerances in the dimensions and parameters of suspended and inverted microstrip lines on the electrical performance of these lines have been studied through sensitivity analysis. The closed-form expressions recently given by Pramanick and Bhartia for the analysis of these lines have been used to derive the mathematical expressions for various sensitivities and the dependence of sensitivities on the aspect ratios and on the substrate dielectric constant has been depicted graphically. Generally speaking, the effects of tolerances are seen to be reflected much more sharply in the sensitivities of the characteristic impedance than in those of the effective dielectric constant. Many other useful inferences are also drawn from the sensitivity graphs. The conclusions are presented in tabular form, so as to be of direct help to the user.