Development of a new HotBalloonTM ablation catheter equipped with a balloon surface temperature monitoring sensor for pulmonary vein isolation.

The balloon surface temperature (BST) should be monitored to ensure the success of the ablation procedure using the HotBalloonTM ablation catheter (HBC) in clinical settings. Therefore, we sought to develop a new HBC equipped with a surface temperature monitoring sensor. The BST was evaluated using a pseudo-tissue model and a thermocouple to imitate catheter insertion into the pulmonary vein. Thermo-fluid analysis with computer-aided engineering (CAE) was performed to analyse the temperature distribution in the catheter and the balloon. The CAE analysis reproduced the results from a pseudo-tissue model experiment and demonstrated that some fluid zones inside the catheter shaft had a nearly identical temperature as the BST during the liquid suction period. The pseudo-tissue model experiment confirmed that the temperature was almost the same between the balloon surface and the position of 5 mm inside the catheter shaft from the proximal end of the balloon. A thermocouple placed at 5 mm or 25 mm from the proximal end of the balloon within the catheter shaft showed an equivalent temperature result. This 5-25-mm distance is acceptable to set the BST monitoring sensor inside the catheter shaft, since the sensor can help accurately estimate the BST.

Effect of unsaturated alkyl chains on transfection activity of poly(amidoamine) dendron-bearing lipids.

In an earlier study, we developed a new type of gene vector using poly(amidoamine) (PAMAM) dendron-bearing lipids and reported that their transfection activity was affected by their structures, such as dendron generation and alkyl chain length. In this study, for improvement of their performance as gene vectors, we examined the effect of unsaturated chains of the dendron-bearing lipids using DL-G1-2C(18), which consists of PAMAM G1 dendron moiety and two octadecyl chains, and achieved the most efficient transfection activity among the dendron-bearing lipids having saturated alkyl chains, and DL-G1-2C(18)-U2, which consists of the same dendron-moiety and two octadecenyl chains. DL-G1-2C(18)-U2 showed a higher ability to form lipoplexes with plasmid DNA than DL-G1-2C(18). The DL-G1-2C(18)-U2 lipoplexes exhibited much smaller particle sizes than the DL-G1-2C(18). In addition, the DL-G1-2C(18)-U2 lipoplexes exhibited more efficient transfection of HeLa cells than DL-G1-2C(18) did. Results demonstrate the importance of unsaturated chains for the production of the dendron-bearing lipids having excellent gene transfection performance. Without the help of additional fusogenic lipids such as dioleoylphosphatidylethanolamine, DL-G1-2C(18)-U2 lipoplexes achieved the highly efficient transfection of the cells without marked cellular toxicity, in the presence of serum. Therefore, DL-G1-2C(18)-U2 might be promising as a potent gene vector.

Polyamidoamine dendron-bearing lipids as a nonviral vector: influence of dendron generation.

Recently, we demonstrated that octadecyl chains are important as alkyl chain moieties of polyamidoamine (PAMAM) dendron-bearing lipids for their serum-resistant transfection activity [Bioconjugate Chem.2007, 18, 1349-1354]. Toward production of highly potent vectors, we examined the influence of the generation of dendron moiety on transfection activity of PAMAM dendron-bearing lipids having two octadecyl chains. We synthesized dendron-bearing lipids with PAMAM G1, G2, and G3 dendrons, designated respectively as DL-G1-2C(18), DL-G2-2C(18), and DL-G3-2C(18). The DL-G2-2C(18) and DL-G3-2C(18) interacted with plasmid DNA effectively and formed stable lipoplexes with small sizes and spherical shape. However, DL-G1-2C(18) interacted with plasmid DNA less effectively and formed tubular-shaped lipoplexes with lower stability and larger size. Cells took up DL-G2-2C(18) and DL-G3-2C(18) lipoplexes efficiently, but cellular uptake of the DL-G1-2C(18) lipoplexes was less efficient. Nevertheless, DL-G1-2C(18) lipoplexes achieved 100-10 000 times higher levels of transgene expression, which was evaluated using luciferase gene as a reporter gene. Confocal scanning laser microscopic analysis of intracellular behaviors of the lipoplexes revealed that DL-G1-2C(18) lipoplexes generated free plasmid DNA molecules in the cytosol more effectively than other lipoplexes did. Moderate binding ability of DL-G1-2C(18) might be responsible for generation of lipoplexes which deliver plasmid DNA into cells, liberate it in the cytoplasm, and induce efficient transgene expression.