A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin–Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of Pseudomonas aeruginosa to the Native Quercetin

Quercetin (QUE)—a plant-derived flavonoid, is recently established as an effective quorum sensing (QS) inhibiting agent in Pseudomonas aeruginosa—the main bacterial pathogen in bronchiectasis lungs. Successful clinical application of QUE, however, is hindered by its low solubility in physiological fluids. Herein we developed a solubility enhancement strategy of QUE in the form of a stable amorphous nanoparticle complex (nanoplex) of QUE and chitosan (CHI), which was prepared by electrostatically driven complexation between ionized QUE molecules and oppositely charged CHI. At its optimal preparation condition, the QUE–CHI nanoplex exhibited a size of roughly 150 nm with a 25% QUE payload and 60% complexation efficiency. The complexation with CHI had no adverse effect on the antibacterial and anticancer activities of QUE, signifying the preservation of QUE’s bioactivities in the nanoplex. Compared to the native QUE, the QUE–CHI nanoplex exhibited superior QS inhibition in suppressing the QS-regulated swimming motility and biofilm formation of P. aeruginosa, but not in suppressing the virulence factor production. The superior inhibitions of the biofilm formation and swimming motility afforded by the nanoplex were attributed to (1) its higher kinetic solubility (5-times higher) that led to higher QUE exposures, and (2) the synergistic QS inhibition attributed to its CHI fraction.

X-ray linear dichroic ptychography

Biominerals such as seashells, coral skeletons, bone, and tooth enamel are optically anisotropic crystalline materials with unique nanoscale and microscale organization that translates into exceptional macroscopic mechanical properties, providing inspiration for engineering new and superior biomimetic structures. Using Seriatopora aculeata coral skeleton as a model, here, we experimentally demonstrate X-ray linear dichroic ptychography and map the c-axis orientations of the aragonite (CaCO3) crystals. Linear dichroic phase imaging at the oxygen K-edge energy shows strong polarization-dependent contrast and reveals the presence of both narrow (<35°) and wide (>35°) c-axis angular spread in the coral samples. These X-ray ptychography results are corroborated by four-dimensional (4D) scanning transmission electron microscopy (STEM) on the same samples. Evidence of co-oriented, but disconnected, corallite subdomains indicates jagged crystal boundaries consistent with formation by amorphous nanoparticle attachment. We expect that the combination of X-ray linear dichroic ptychography and 4D STEM could be an important multimodal tool to study nano-crystallites, interfaces, nucleation, and mineral growth of optically anisotropic materials at multiple length scales.

In vivo antiplasmodial potential of Carrageenan and Prosopis africana buccal films of artemether on malariogenic mice

Objective: To deliver bioadhesive buccal films of artemether (ART) with ability to adhere, hydrate and release drug across the buccal membrane. Methods: Buccal films prepared by film casting using carrageenan (CAR) and Prosopis africana (PRO) were characterized by size, zeta potential, texture, water content, morphology, thermal and interaction studies, in vitro and in vivo antiplasmodial activity in mice. Results: Films were stable with sizes (2442 and 835 nm), water content (21 and 15 %), bioadhesivity (24 and 9.4 %) and film thickness (0.18 and 0.28 mm) for CARART and PROART respectively. Enthalpy of CARART, PROART and ART were 76, 22 and 88 J/g where as parasitaemia reduction of 67 and 76 % were observed for CARART and PROART respectively. Conclusion: Though CARART had better water content and bioadhesivity necessary for film hydration at buccal membrane, PROART eventually had superior buccal performance perhaps due to its film thickness and amorphous nanoparticle subdivision. Key words: Artemether; Carrageenan; Prosopis africana; Sublingual buccal films; Malaria