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.     

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.     

Zein-based anti-browning cling wraps for fresh-cut apple slices

The usage of cling wraps is emerging as an easy and cost-effective approach to protect fresh-cut fruits and vegetables from dust, whilst improving visual appeal on retail counters. This study focused on developing an alternate, protein-based packaging material as a food grade cling wrap for food packaging applications. Zein-based cling wraps were produced, and their physical and mechanical characteristics were evaluated and compared with conventionally used chitosan biopolymer films and commercial synthetic polymer films. Antioxidant potential of the prepared films was studied, and the effectiveness of the developed films as anti-browning cling wraps was evaluated using studies conducted on fresh-cut apple slices at ambient conditions. Anti-browning effects were in par with polymeric counterparts; however, zein cling wraps could better prevent weight loss in apple slices. Zein-based films can be adopted as biodegradable food grade cling wraps as an alternative to chitosan and synthetic polymeric materials.