A series of amphiphilic nitric oxide (NO)-releasing poly(amidoamine) (PAMAM) dendrimers with different exterior functionalities were synthesized by a ring-opening reaction between primary amines on the dendrimer and propylene oxide (PO), 1,2-epoxy-9-decene (ED), or a ratio of the two, followed by reaction with NO at 10 atm to produce N-diazeniumdiolate-modified scaffolds with a total storage of ~1 μmol/mg. The hydrophobicity of the exterior functionality was tuned by varying the ratio of PO and ED grafted onto the dendrimers. The bactericidal efficacy of these NO-releasing vehicles against established Gram-negative Pseudomonas aeruginosa biofilms was then evaluated as a function of dendrimer exterior hydrophobicity (i.e., ratio of PO/ED), size (i.e., generation), and NO release. Both the size and exterior functionalization of dendrimer proved important to a number of parameters including dendrimer-bacteria association, NO delivery efficiency, bacteria membrane disruption, migration within the biofilm, and toxicity to mammalian cells. Although enhanced bactericidal efficacy was observed for the hydrophobic chains (e.g., ED), toxicity to L929 mouse fibroblast cells was also noted at concentrations necessary to reduce bacterial viability by 5-logs (99.999% killing). The optimal PO to ED ratios for biofilm eradication with minimal toxicity against L929 mouse fibroblast cells were 7:3 and 5:5. The study presented herein demonstrated the importance of both dendrimer size and exterior properties in determining efficacy against established biofilms without compromising biocompatibility to mammalian cells.

S-nitrosothiol-modified chitosan oligosaccharides were synthesized by reaction with 2-iminothiolane hydrochloride and 3-acetamido-4,4-dimethylthietan-2-one, followed by the thiol nitrosation. The resulting nitric oxide (NO)-releasing chitosan oligosaccharides stored ~0.3 μmol NO/mg chitosan. Both the chemical structure of the nitrosothiol (i.e., primary and tertiary) and the use of ascorbic acid as a trigger for NO donor decomposition were used to control the NO-release kinetics. With ascorbic acid, the S-nitrosothiol-modified chitosan oligosaccharides elicited a 4-log reduction in Pseudomonas aeruginosa (P. aeruginosa) viability. Confocal microscopy indicated that the primary S-nitrosothiol-modified chitosan oligosaccharides associated more with the bacteria relative to the tertiary S-nitrosothiol system. The primary S-nitrosothiol-modified chitosan oligosaccharides elicited minimal toxicity towards L929 mouse fibroblast cells at the concentration necessary for a 4-log reduction in bacterial viability, further demonstrating the potential of S-nitrosothiol-modified chitosan oligosaccharides as NO-release therapeutics.

The stability of low-pressure chemical vapor-deposited TiB2 films has been investigated for their potenital use as diffusion barriers between A1 or Cu metallurgy and the Si substrate during post-metal annealing at temperatures ranging from 450-640~ for A1, and 500-800~ for Cu. Although no evidence of intermixing was observed via Rutherford backscattering spectroscopy (RBS) for TiB2/Si samples rapid thermal-annealing (RTA) up to 1080~ pyramid-shape pits in the Si, bounded by (111) planes, were observed using transmission electron microscopy for the samples annealed above 950~ Secondary ion mass spectroscopy depth profiles of B in Si originating from the TiB2 solid source suggested enhanced diffusion after RTA. According to RBS spectra coupled with scanning electron microscopy (SEM) examination, A1/TiB2/Si (pre-annealed) stacks appeared to be stable up to 500~ for 30 min in forming gas. For the stacks with as-deposited (amorphous) TiB2 films, plan-view SEM of A1/TiB2/Si showed very limited reaction with A1 up to 600~ in good agreement with sheet resistance measurements. The as-deposited, amorphous TiB2 films were superior diffusion barriers compared to the annealed, polycrystalline TiB2. No interaction took place between sputtered Cu and an underlying, amorphous TiB2 film up to 750~ 30 min in vacuum. Plan-view SEM, RBS, and sheet resistance measurements showed that the structure started to break down at 775~