Objective. To determine the efficacy of local therapy with human angiostatin gene in murine collageninduced arthritis (CIA).Methods. DBA/1 mice were immunized with bovine type II collagen. Before the onset of arthritis, NIH3T3 fibroblasts, transduced with angiostatinexpressing retroviral vectors or control vectors, were transplanted into the knee cavity. The incidence of arthritis in the knee joints was evaluated histologically based on pannus formation and cartilage destruction. Paws were evaluated macroscopically for redness, swelling, and deformities and immunologically for levels of interleukin-1␤. Angiogenesis in paws and knee joints was studied by immunohistochemistry using anti-CD31 antibody and measurement of von Willebrand factor levels.Results. Pannus formation and cartilage erosion were dramatically reduced in knees transplanted with angiostatin-expressing cells. In addition, the onset of CIA in the ipsilateral paws below the knees injected with the angiostatin gene was significantly prevented. Furthermore, angiostatin gene transfer inhibited arthritisassociated angiogenesis.Conclusion. Local production of angiostatin in the knee was able to prevent the onset of CIA not only in the knee injected with genetically engineered cells, but also in the uninjected ipsilateral paw. This suggests that transfer of the angiostatin gene, and potentially also its protein, may provide a new, effective approach to the treatment of rheumatoid arthritis.

A simultaneous volumetric thickness-profile measurement method based on an acousto-optic tunable filter for transparent film deposited upon pattern structures is described. The nondestructive thickness profilometer prevents the destruction of samples such as one encounters in using a scanning-electron microscope and provides good accuracy. The information on the volumetric thickness profile is obtained through least-squares fitting with a phase model, ø(model)(k)=2kh+? (k, d)+(offset) , which has three unknowns: surface profile h, thickness d, and an indeterminate initial phase offset. Accurate phase information in the spectral domain can be obtained by introduction of the concept of spectral carrier frequency. Experimental results for a metal patterned sample show that the volumetric thickness profile can be determined within an error range of ~10 nm .

These results demonstrate that most HDI studies so far have examined PK interactions and have been limited to very few conventional drugs and herbal drugs. This suggests that more studies focusing on PD are necessary to understand interactions between commonly used herbal and conventional drugs.

In this study, a combined system of microneedles and a triboelectric nanogenerator (TENG) has been developed for drug delivery. A triboelectric device, which converts mechanical energy into alternating current (AC), was chosen to replace the electrophoresis (EP) effect. To directly generate triboelectricity from salmon deoxyribonucleic acid (SDNA)-based microneedles, a triboelectric series of SDNA film and chargeable polymers (polyimide and Teflon) was studied. The electrical output of the two charged polymers was compared to find a material that could be highly charged with SDNA. The electrical output was also compared as a function of the concentration of a drug embedded in the SDNA film, and the results confirmed that drug intercalation affected the carrier diffusion. The mechanical strength of the microneedles was assessed by histological analysis of their penetration into porcine cadaver skin. Furthermore, the output voltage of a system incorporating microneedles and TENG in cadaver skin, and in vitro drug release into gelatin were evaluated to examine potential application as an electrically active drug delivery system. The electrical output voltage of this system was ∼95 V. The mechanism of triboelectric perturbation to the skin has also been discussed. The system developed in this work is a new, facile approach toward effective drug delivery that replaces the existing EP method and expands the application of TENGs.