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.     

Investigation on external stimuli engendered magnetic ordering in polycrystalline CaCu3Ti4O12 quadruple perovskite

The consequences of high energy mechanical milling, microwave-assisted heating and rapid thermal cooling on magnetic ordering in polycrystalline CaCu₃Ti₄O₁₂ cubic perovskite have been investigated by means of X-ray powder diffractometry (300?K), dc magnetization in field – cooled and zero – field cooled modes (H = 100?Oe and 1000?Oe, T?=?5–300?K) (M – T curves) and M – H loop characteristics (T?=?5?K and 300?K, H_max = 70?kOe). The M – T curves of unmilled and 16?h milled samples show pure antiferromagnetic and weak ferromagnetic ordering, respectively, 1?h and 6?h milled samples demonstrate the coexistence of both the phases while microwave-assisted and quenched samples exhibit classic antiferromagnetic transition and a low temperature paramagnetic–like contribution with different weights, well supported by the M – H loop characteristics. The observed transformations in the magnetic ordering are attributed to the ball-milling induced stress which curtails hybridization of empty Ti-3d orbitals with Cu-3d and O-2p orbitals and secondary phase formation. Oxygen vacancies associated with bound magnetic polarons originate ferromagnetism in the milled samples while unpaired electrons inhabited at the empty sites are the cause of paramagnetic centers. The low-temperature Curie – tail in M – T curve for quenched and microwave assisted samples is attributed to Ti³⁺ cations.     

Method for Predicting the Strength of Pellets Produced from Dry Fine-Grained Materials

Powder Metallurgy and Metal Ceramics - The mechanisms of phase interactions in granular media were studied to elaborate the results obtained previously at the Nekrasov Iron and Steel Institute of...     

Identifying crop water stress using deep learning models

Neural Computing and Applications - The identification of water stress is a major challenge for timely and effective irrigation to ensure global food security and sustainable agriculture. Several...     

The use of natural (Pinus pinaster) resin in the production of printing ink and the printability effect

Alkyd resins are generally used in the production of printing inks. All industries look for alternative raw materials in the production of ink with the growing inclination toward using natural products. Resins forming the vehicle of the ink to be obtained from natural resources will provide benefits for the environment, nature, and living creatures. The aim of the study was to promote the use of natural resin in the ink system. Natural Pinus pinaster resin was added into vegetable and mineral oil-based solvents in pure form with alkyd resin in different amounts and ink varnishes of different combinations were prepared. Then, printing inks were produced from these varnishes in pure and hybrid form. Following the assessment of the rheological properties of the inks prepared, printing tests were conducted to assess the printing quality parameters. Ideal mixing ratios of the natural resins in the ink were determined for printability. The environmental importance and advantages of the use of natural resins were discussed. Recommendations were given in line with the results to encourage widespread use of natural resins in near future.     

Methyltransferase Contingencies in the Pathway of Everninomicin D Antibiotics and Analogues

Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A₁, C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A₁- and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A₁-ring phenol and H-ring C-4’ hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates.