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.     

Design of 5.9 ghz dsrc-based vehicular safety communication

The automotive industry is moving aggressively in the direction of advanced active safety. Dedicated short-range communication (DSRC) is a key enabling technology for the next generation of communication-based safety applications. One aspect of vehicular safety communication is the routine broadcast of messages among all equipped vehicles. Therefore, channel congestion control and broadcast performance improvement are of particular concern and need to be addressed in the overall protocol design. Furthermore, the explicit multichannel nature of DSRC necessitates a concurrent multichannel operational scheme for safety and non-safety applications. This article provides an overview of DSRC based vehicular safety communications and proposes a coherent set of protocols to address these requirements     

A Monte Carlo simulation study of the mechanical and conformational properties of networks of helical polymers. I. General concepts

We study the mechanical and conformational properties of networks of helical polymers with a combination of Monte Carlo simulations based on the Wang-Landau algorithm and the three-chain model. We find that the stress-strain behavior of these networks has novel features not observed in typical networks made of synthetic polymers. In particular, we find that as these networks are stretched they first strengthen, then soften and finally strengthen again. This non-monotonic behavior of the stress correlates with the one of the helical content and is rationalized by the elongation-induced formation and melting of the helical structure of the polymer. We complement these results with a study of other conformational properties of the polymer strands that clarify the molecular mechanisms behind the mechanical behavior of these networks. Finally, we present a qualitative comparison of some of our results with the theoretical ones recently reported by Kutter and Terentjev.     

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.     

Speed Control of DC Motor with MRPID Controller in the Presence of Noise

Speed control of a DC motor has always been a challenge because of its variable torque. But it becomes more challenging when noise enters the system at its input. Therefore, there is a need of more advanced controllers. In this paper, a multi-resolution proportional integral derivative (MRPID) controller has been proposed to be utilized to control the speed of a DC motor. It works well even in the presence of noise as compared to the conventional PID controller. Also, performance of a PID controller deteriorates when nonlinearity or uncertainty arises in the system. This degraded performance can be improved by utilizing the multi-resolution property of wavelets, which decomposes the error signal into various frequency components. Further, wavelet coefficients of these decompositions are used to generate the control signal for controlling speed of a DC motor. In this paper, performances of a MRPID, a fractional order PID (FOPID) and a conventional PID controllers are compared in the presence of noise for speed control of a DC motor. The results obtained using a MRPID controller are observed to be better in terms of improved transient characteristics and disturbance rejection for a DC motor as compared to those obtained with PID and FOPID controllers.

     

Enhanced photoluminescence from CdS nanocrystals encapsulated by PVP and SHMP

The effects of the stabilizing agent on the structural and luminescence properties of cadmium sulfide (CdS) nanocrystals have been investigated. Samples were prepared by chemical precipitation method using sodium hexametaphosphate (SHMP) and polyvinyl pyrrolidone (PVP). The structural and optical properties have been studied by X-ray diffraction (XRD), ultraviolet-visible (UV-Vis) absorption, photoluminescence (PL) and Fourier transform infrared (FTIR) spectroscopy. XRD patterns confirm the presence of cubic zinc blend crystal structure with space group F-43m. The results show the variation in crystallite size with change in surfactant. Blue shift in absorption edge as compared to bulk CdS is found. PL results represent broad and very intense red emission with smaller particle size due to modification of surface emitting states with surfactant.     

Antineoplastic and antioxidant potential of phycofabricated silver nanoparticles using microalgae Chlorella minutissima

This study for the first time reports on fresh water microalgae Chlorella minutissima aqueous extract (CmAe) which was utilized for the biogenic synthesis of silver nanoparticles and tested their antineoplastic potential against Liver Hepatocellular Carcinoma (HepG2) cell line. The characteristic colour change of the reaction mixture from greenish yellow to yellowish brown confirmed the synthesis of Chlorella minutissima silver nanoparticles (CmAgNPs). Microscopic analysis revealed CmAgNPs to be spherical‐shaped with particle size ranging from 10 to 30 nm. The carbohydrates and proteins distinctive peaks were observed in Fourier transform infrared spectroscopy (FTIR) spectra which suggested these biomolecules acted as reducing and capping agents. Further, the crystalline nature of CmAgNPs was confirmed by X‐ray diffraction (XRD) analysis. CmAgNPs showed maximum free radical scavenging proving it to be more potent antioxidant agent as compared to CmAe. The mortality rate of HepG2 cells treated with CmAgNPs was found to be 91.8 % at 120 μg/ml with IC₅₀ value 12.42 ± 1.096 μg/ml after 48 h whereas no effect was observed on normal Human Embryonic Kidney (HEK 293) cells. Fluorescent images of the treated HepG2 cells revealed the formation of apoptotic bodies, condensed nuclei and cell shrinkage indicating their effectiveness against the cancer cells.Inspec keywords: silver, nanoparticles, nanomedicine, microorganisms, cellular biophysics, nanofabrication, scanning electron microscopy, transmission electron microscopy, atomic force microscopy, proteins, Fourier transform infrared spectra, molecular biophysics, X‐ray chemical analysis, X‐ray diffraction, kidney, cancer, biomedical materialsOther keywords: antineoplastic potential, antioxidant potential, phycofabricated silver nanoparticle, Chlorella minutissima, freshwater microalgae, aqueous extract, liver hepatocellular carcinoma cell line, CmAgNP synthesis, field emission scanning electron microscopy, high‐resolution transmission electron microscopy, atomic force microscopy, dynamic light scattering, carbohydrate, protein, Fourier transform infrared spectroscopy, biomolecule, energy‐dispersive X‐ray spectroscopy, elemental silver signal, CmAgNP crystalline, X‐ray diffraction analysis, antioxidant agent, HepG2 cell mortality rate, human embryonic kidney, HEK 293 cell, fluorescent image, apoptotic body formation, condensed nuclei, cell shrinkage, cancer cell, antineoplastic agent, Ag     

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.