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.     

Influence of Mg concentration on structural,morphological and optical properties of nanoceria

Nano crystalline pure and Mg doped ceriaparticles were synthesized by simple chemical co-precipitation method using cerium nitrate hexahydrate as a source material and magnesium nitrate as doping precursor at room temperature. The effect of doping were investigated by X-ray diffraction pattern(XRD), FT-Raman,fourier transform infrared spectroscopy(FTIR), Ultraviolet spectroscopy(UV), photoluminescence spectroscopy(PL), field emission scanning electron microscope(FESEM) and high resolution transmission electron microscopy with energy dispersive spectroscopy (HRTEM &EDS). The X-ray diffraction pattern and FT-Raman studies showed that the prepared samples were nano particulates with cubic fluorite structure. The XRD pattern analysis showed that the size of the particles ranged from 13 to 20?nm, however 4?wt% Mg doping results in reduction of particle size compared with other doping concentrations. The effects of Mg concentration on various structural parameters of the prepared samples were also determined. The slight blue shift observed upon doping in UV–Vis absorption region around 330–360nmrecorded for reduction in particle size. The FTIR unveils the presence of Metal oxygen bonds below 700?cm^?1in the prepared samples. All samples showed a broad emission band at 430?nm with linearly increasing intensity with respect to dopant concentrations. The Spherical morphology with weak agglomeration was identified through FESEM and HRTEM analysis. The elemental analysis of Ce, O and Mg were confirmed through EDS analysis.     

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.     

BUBBLE TEMPERATURES OF THE BINARY MIXTURES OF 1,2-DIMETHYLBENZENE WITH 2-PROPANOL, 1-BUTANOL, 2-BUTANOL, 2-METHYLPROPAN-1-OL AND 2-METHYLPROPAN-2-OL AT 95 kPa

Bubble temperatures at 95 kPa over the entire composition range are measured for the five binary systems formed by 1,2-dimethylbenzene with 2-propanol, 1-butanol, 2-butanol, 2- methylpropan-1-ol, and 2-methylpropan- 2-ol. A Swietoslawski - type ebulliometer was used for the measurements. The composition versus temperature measurements are well represented by the Wilson model.     

Effect of organic modifiers on dynamic and static nanomechanical properties and crystallinity of intercalated clay–polycaprolactam nanocomposites

Polymer clay nanocomposites (PCN) of Polyamide6 and sodium montmorillonite are prepared using different organic modifiers (12‐aminolauric acid, n‐dodecylamine, and 1,12‐diaminododecane) to study effect of organic modifiers on structure and nanomechanical properties of PCN. Using X‐ray diffraction and differential scanning calorimetry, crystalline nature of PCNs are evaluated. Nanoscale viscoelastic properties of PCNs are evaluated using nanodynamic mechanical analyzer (NanoDMA). Nanoscale elastic modulus and hardness of PCNs are evaluated using nanoindenter. PCNs show enhancement in elastic modulus, storage modulus, loss modulus, and loss factor by maximum amount of 62.88%, 56.38%, 145.74%, and 71.43%, respectively, and decrease in percentage crystallinity by 16.52% compared to pure polymer. This result indicates that organic modifiers have effect on crystallinity and nanomechanical properties of PCN. To evaluate effect of clay loading on nanomechanical properties of PCN, PCN containing 12‐aminolauric acid is synthesized with different weight percent (3, 6, and 9% of weight of polymer) of organically modified montmorillonite (OMMT), which shows that nanomechanical properties of PCN improves with increase in clay loading. Our study reveals that change in crystallinity of polymer in PCN may have role in the enhancement of nanomechanical properties of PCNs in comparison to pristine polymer. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

How In-Home Technologies Mediate Caregiving Relationships in Later Life

In-home technologies can support older adults' activities of daily living, provide physical safety and security, and connect elders to family and friends. They facilitate aging in place while reducing caregiver burden. One of older adults' primary concerns about in-home technologies is their potential to reduce human contact, particularly from cherished caregivers. In this exploratory in situ study, we provided an ecosystem of networked monitoring technologies to six older adults and their caregivers. We analyzed the amount and content of communication between them. The amount of noncomputer-mediated communication did not decrease through the 6-week study. The content of communication coalesced into four themes: communication about the technologies, communication facilitated by technologies, intrusiveness of technologies, and fun and playfulness with the technologies. Results suggest that in-home technologies, designed with sensitivity to older adults' primary motivations, have the potential to shape and tailor important relationships in later life.     

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.     

Implementation of VLSI on Signal Processing-Based Digital Architecture Using AES Algorithm

Continuous improvements in very-large-scale integration (VLSI) technology and design software have significantly broadened the scope of digital signal processing (DSP) applications. The use of application-specific integrated circuits (ASICs) and programmable digital signal processors for many DSP applications have changed, even though new system implementations based on reconfigurable computing are becoming more complex. Adaptable platforms that combine hardware and software programmability efficiency are rapidly maturing with discrete wavelet transformation (DWT) and sophisticated computerized design techniques, which are much needed in today’s modern world. New research and commercial efforts to sustain power optimization, cost savings, and improved runtime effectiveness have been initiated as initial reconfigurable technologies have emerged. Hence, in this paper, it is proposed that the DWT method can be implemented on a field-programmable gate array in a digital architecture (FPGA-DA). We examined the effects of quantization on DWT performance in classification problems to demonstrate its reliability concerning fixed-point math implementations. The Advanced Encryption Standard (AES) algorithm for DWT learning used in this architecture is less responsive to resampling errors than the previously proposed solution in the literature using the artificial neural networks (ANN) method. By reducing hardware area by 57%, the proposed system has a higher throughput rate of 88.72%, reliability analysis of 95.5% compared to the other standard methods.