Delivery by shock waves of active principle embedded in gelatin-based capsules

PURPOSE: Delivering a drug close to the targeted cells improves its benefit versus risk ratio. A possible method for local drug delivery is to encapsulate the drug into solid microscopic carriers and to release it by ultrasound. The objective of this work was to use shock waves for delivering a molecule loaded in polymeric microcapsules. MATERIAL AND METHODS: Ethyl benzoate (EBZ) was encapsulated in spherical gelatin shells by complex coacervation. A piezocomposite shock wave generator (120 mm in diameter, focused at 97 mm, pulse length 1.4 micros) was used for sonicating the capsules and delivering the molecule. Shock parameters (acoustic pressure, number of shocks and shock repetition frequency) were varied in order to measure their influence on EBZ release. A cavitation-inhibitor liquid (Ablasonic) was then used to evaluate the role of cavitation in the capsule disruption. RESULTS: The measurements showed that the mean quantity of released EBZ was proportional to the acoustic pressure of the shock wave (r2 > 0.99), and increased with the number of applied shocks. Up to 88% of encapsulated EBZ could be released within 4 min only (240 shocks, 1 Hz). However, the quantity of released EBZ dropped at high shock rates (above 2Hz). Ultrasound imaging sequences showed that cavitation clouds might form, at high shock rates, along the acoustic axis making the exposure inefficient. Measurements done in Ablasonic showed that cavitation plays a major role in microcapsules disruption. CONCLUSIONS: In this study, we designed polymeric capsules that can be disrupted by shock waves. This type of microcapsule is theoretically a suitable vehicle for carrying hydrophobic drugs. Following these positive results, encapsulation of drugs is considered for further medical applications.     

Emission control in broad periodic waveguides and critical coupling

Broad periodic channel waveguides, with a corrugation on their edge, exhibit a remarkable structure in their dispersion diagram, in the form of stripes of minigaps, whose hyperbolic shape is demonstrated. Around the Brillouin zone edge, the contra-directional feedback borrows the geometry of Littrow diffraction. Spontaneous emission from a large subset of modes then acquires a strong modulation. Lasing on these modes, the so-called “Littrow lasing”, offers also the lowest lasing threshold of the open resonator system. Reviewing our recent studies of this system, we discuss slow light and critical coupling phenomena: for a properly adjusted contra-directional coupling, the bands become substantially flat in a sizable area of the dispersion diagram, opening various perspectives. The band engineering tools to master these phenomena and the physical implications in other domains are briefly reviewed.     

Synthesis and Structure–Activity Relationship Studies of Pyrido [1,2-e]Purine-2,4(1H,3H)-Dione Derivatives Targeting Flavin-Dependent Thymidylate Synthase in Mycobacterium tuberculosis

In 2002, a new class of thymidylate synthase (TS) involved in the de novo synthesis of dTMP named Flavin-Dependent Thymidylate Synthase (FDTS) encoded by the thyX gene was discovered; FDTS is present only in 30% of prokaryote pathogens and not in human pathogens, which makes it an attractive target for the development of new antibacterial agents, especially against multi-resistant pathogens. We report herein the synthesis and structure-activity relationship of a novel series of hitherto unknown pyrido[1,2-e]purine-2,4(1H,3H)-dione analogues. Several synthetics efforts were done to optimize regioselective N¹-alkylation through organopalladium cross-coupling. Modelling of potential hits were performed to generate a model of interaction into the active pocket of FDTS to understand and guide further synthetic modification. All those compounds were evaluated on an in-house in vitro NADPH oxidase assays screening as well as against Mycobacterium tuberculosis ThyX. The highest inhibition was obtained for compound 23a with 84.3% at 200 µM without significant cytotoxicity (CC₅₀ > 100 μM) on PBM cells.     

Synthesis and Properties of the Perfluoroethyl Martin Silicate: Reactivity in Solution and Solid-State Mechanochemistry

We herein report the first synthesis of a Martin silicate bearing a pentafluoroethyl chain. The full characterisation of this new pentacoordinated silicon species is detailed. Insights on its electronic properties based on structural, physicochemical and computational data are provided. A comparative study of reactivity in solution and in solid state by mechanochemistry has been performed in order to assess the ability of this bench-stable salt to act as a safe C₂F₅-alkylation reagent in a nucleophilic or radical manner.