Zeolite-loaded alginate-chitosan hydrogel beads as a topical hemostat.

Hemorrhage is the leading cause of preventable death after a traumatic injury, and the largest contributor to loss of productive years of life. Hemostatic agents accelerate hemostasis and help control hemorrhage by concentrating coagulation factors, acting as procoagulants and/or interacting with erythrocytes and platelets. Hydrogel composites offer a platform for targeting both mechanical and biological hemostatic mechanisms. The goal of this work was to develop hydrogel particles composed of chitosan, alginate, and zeolite, and to assess their potential to promote blood coagulation via multiple mechanisms: erythrocyte adhesion, factor concentration, and the ability to serve as a mechanical barrier to blood loss. Several particle compositions were synthesized and characterized. Hydrogel bead composition was optimized to achieve the highest swelling capacity, greatest erythrocyte adhesion, and minimal in vitro cytotoxicity. These results suggest a polymer hydrogel-aluminosilicate composite material may serve as a platform for an effective hemostatic agent that incorporates multiple mechanisms of action. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1662-1671, 2018.

Hydroxylated Dimeric Naphthoquinones Increase the Generation of Reactive Oxygen Species, Induce Apoptosis of Acute Myeloid Leukemia Cells and Are Not Substrates of the Multidrug Resistance Proteins ABCB1 and ABCG2.

Selective targeting of the oxidative state, which is a tightly balanced fundamental cellular property, is an attractive strategy for developing novel anti-leukemic chemotherapeutics with potential applications in the treatment of acute myeloid leukemia (AML), a molecularly heterogeneous disease. Dimeric naphthoquinones (BiQs) with the ability to undergo redox cycling and to generate reactive oxygen species (ROS) in cancer cells are a novel class of compounds with unique characteristics that make them excellent candidates to be tested against AML cells. We evaluated the effect of two BiQ analogues and one monomeric naphthoquinone in AML cell lines and primary cells from patients. All compounds possess one halogen and one hydroxyl group on the quinone cores. Dimeric, but not monomeric, naphthoquinones demonstrated significant anti-AML activity in the cell lines and primary cells from patients with favorable therapeutic index compared to normal hematopoietic cells. BiQ-1 effectively inhibited clonogenicity and induced apoptosis as measured by Western blotting and Annexin V staining and mitochondrial membrane depolarization by flow cytometry. BiQ-1 significantly enhances intracellular ROS levels in AML cells and upregulates expression of key anti-oxidant protein, Nrf2. Notably, systemic exposure to BiQ-1 was well tolerated in mice. In conclusion, we propose that BiQ-induced therapeutic augmentation of ROS in AML cells with dysregulation of antioxidants kill leukemic cells while normal cells remain relatively intact. Further studies are warranted to better understand this class of potential chemotherapeutics.