Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels.

Control over of biological processes can potentially be therapeutically regulated through localized biomolecular deliveries. While implantable hydrogels can provide localized therapeutic deliveries, they do not traditionally provide the temporally complex therapeutic delivery profiles required to regulate complex biological processes. Ionically crosslinked alginate hydrogels have been shown to release encapsulated payloads in response to a remotely applied ultrasonic stimulus, thus potentially enabling more temporally complex therapeutic delivery profiles. However, thorough characterizations of how different types of therapeutic payloads are retained and ultrasonically released need to be performed. Additionally, the impact of potentially disruptive ultrasonic stimulations on hydrogel structure and temperature need to be characterized to better understand what range of ultrasonic signals can be used to trigger release. To perform these characterizations, calcium-crosslinked alginate hydrogels were loaded with various model macromolecules (dextrans), chemotherapeutics, and protein signaling factors and exposed to a variety of single-pulse and multi-pulse ultrasonic signals at various amplitudes and durations. In response to single-pulsed ultrasonic exposures, quantifications of molecular release, degree of gel erosion, and increase in hydrogel temperature revealed that the ultrasonic stimulations required for statistically significant therapeutic deliveries often eroded and heated the gels to unacceptable levels. However, multi-pulse ultrasonic exposures were shown to achieve significant amounts of therapeutic release while keeping gel erosion and temperature increase at modest levels. Finally, experiments were performed demonstrating that ultrasonic stimulation could be used to generate drug release profiles shown to have potential therapeutic benefits (e.g., pulsatile and sequential anticancer delivery profiles). This work underscores the potential of using ultrasonically responsive polymeric hydrogels for providing on-demand control over more complex therapeutic deliver profiles and enhancing drug delivery strategies in cancer therapies and beyond.

Physicochemical implications of cyanobacteria oxidation with Fe(VI).

Increases in harmful algal blooms has negatively impacted many surface-sourced drinking water utilities. To control these blooms, many water utilities implement pre-oxidation with ozone, chlorine, or permanganate; however, pre-oxidation of algae has both positive and negative water quality outcomes. This study investigated ferrate (Fe(VI)) as an alternative oxidant by measuring its effect on cell lysing, surface characteristics, and coagulation in waters containing the cyanobacteria Microcystis aeruginosa. Bench scale studies were conducted to examine the complex combination of processes in a Fe(VI)-algae system. These processes were characterized by fluorescence index, surface charge, collision frequency modeling, particle counts and sphericity, total nitrogen, and ferrate decomposition measurements. Results showed that Fe(VI) lysed algal cells, but further oxidation of released organic matter is possible. The presence of algae did not significantly impact the rate of Fe(VI) decomposition. Fe(VI) pre-oxidation may also be capable of decreasing the formation of nitrogenated disinfection byproducts through subsequent oxidation of released nitrogen rich organic matter. Streaming current and zeta potential results indicate destabilization of the resulting algae and iron suspension was incomplete under most conditions. Particle collision frequency modeling indicates fluid shear to be an important aggregation mechanism of the resulting suspension. Overall, Fe(VI) is a viable alternative to other strong oxidants for water utilities struggling with harmful algal blooms, but the final fate of the resulting organic matter must be further studied.