No abstract

A series of mesoporous nanosphere materials that are functionalized with various terminal and bridging organic groups were synthesized. They have improved adsorption capacity and different release properties for drug and small molecules. The materials contained terminal vinyl, 3-mercaptopropyl, 3-aminopropyl, and secondary amine functional groups and bridging ethane, ethene, and benzene groups within their mesopore channel walls. The samples containing mercaptopropyl and vinyl groups showed greater adsorption capacity and better controlled release behavior for rhodamine 6G molecules. On the other hand, mesoporous matrices containing amine functional groups showed higher adsorption capacity and better release properties for ibuprofen molecules. Further studies revealed that the bridging organic groups in the mesopore channel walls also improved the adsorption capacity and release properties of the materials compared to the corresponding samples containing no bridging organic groups. Such improved adsorption and controlled release properties of molecules by simple changes of functional groups on mesoporous materials are important for the development of nanomaterial drug delivery vehicles and for controlled release of drugs over long time periods at specific targeted sites in the body. By judicious choice of organic groups and by systematic design and synthetic approaches, nanoporous materials having different adsorption capacity and release properties for many other drug molecules can also be achieved.

Activated neutrophils, recruited to the airway of diseased lung, release human neutrophil peptides (HNP1–4) that are cytotoxic to airway cells as well as microbes. Airway epithelial cells express arginine-specific ADP-ribosyltransferase (ART)-1, a glycophosphatidylinositol-anchored ART that transfers ADP-ribose from NAD to arginines 14 and 24 of HNP-1.We previously reported that ADP-ribosyl-arginine is converted non-enzymatically to ornithine and that ADP-ribosylated HNP-1 and ADP-ribosyl-HNP-(ornithine) were isolated from bronchoalveolar lavage fluid of a patient with idiopathic pulmonary fibrosis, indicating that these reactions occur in vivo. To determine effects of HNP-ornithine on the airway, three analogs of HNP-1, HNP-(R14orn), HNP-(R24orn) and HNP-(R14,24orn) were tested for their activity against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus, their cytotoxic effects on A549, NCI-H441, SAEC epithelial-like cells and normal human lung fibroblasts (NHLF) and their ability to stimulate IL-8 and TGF-β1 release from A549 cells, and to serve as ART1 substrates. HNP and the three analogs had similar effects on IL-8 and TGF-β1 release from A549 cells and were all cytotoxic for SAEC, NCI-H441 and NHLF. HNP-(R14,24orn) when compared to HNP-1 and HNP-1 with a single ornithine substitution for arginine 14 or 24 exhibited reduced cytotoxicity, but it enhanced proliferation of A549 cells and had antibacterial activity. Thus, arginines 14 and 24, which can be ADP-ribosylated by ART1, are critical to the regulation of the cytotoxic and antibacterial effects of HNP-1. The HNP analog, HNP-(R14,24orn) lacks the epithelial cell cytotoxicity of HNP-1 but partially retains its antibacterial activity and thus may have clinical applications in airway disease.