To enhance drug delivery performance of drug eluting balloon (DEB) against re-stenosis, we have proposed a heating drug delivery during balloon dilatation using our laser driven short-term thermal angioplasty which may realize to suppress surrounding thermal injury. We studied an influence of vessel dilatation parameters on the heating drug delivery. These parameters were classified into two different forces, that is, circumferential tension and inter-luminal pressure. We think these parameters were not able to determine only by balloon pressure. The circumferential tension with 0—30 mN/mm<sup>2</sup> was added to a porcine carotid artery using an automatic stage. Various temperature solutions with 37, and 70°C of hydrophobic fluorescent Rhodamine B with 3 μg/ml in concentration were dropped on pig carotid wall. We measured a defined drug delivery amount as well as delivery depth by a microscopic fluorescence measurement on the cross section of the solution delivered vessel. In the case of 37°C, we found the intima surface drug amount with 7 mN/mm<sup>2</sup> was increased as 10-20 times as other tension cases. On the other hand, at 70°C, we found the optimum tension with 30 mN/mm<sup>2</sup>. We found the drug delivery enhancement might be related to the change of super microscopic surface structure of the vessel. We predict that the collagen thermal denaturation of the vessel wall might play important role to the drug delivery.
To enhance drug delivery performance of popular drug eluting balloon against re-stenosis after angioplasty, we have an idea regarding to adjacent use of our unique laser driven thermal balloon of which characteristics could realize short term and uniform temperature elevation to modify drug delivery characteristics. We have already reported a delivery enhancement effect using this idea, however, detailed characteristics have not been studied yet. We studied balloon dilatation in terms of vascular circumferential tension on the heating drug delivery performance using porcine carotid artery wall ex vivo. The extracted carotid artery was used and circumferential tension of 0-30 mN/mm<sup>2</sup> was added. Heating drug delivery was performed on this carotid artery with the heated solution of hydrophobic fluorescent Rhodamine B with 3 μg/ml in concentration at 37 and 70°C. We obtained a defined drug delivery quantity as well as delivery depth by a microscopic fluorescence measurement on a cross section of the drug delivered vessel wall. In the cases of 70°C, we found the drug penetration increase against 3°C case. We predict that the collagen thermal denaturation of the vessel wall may play important role to this penetration. In the case of 3°C, we found the drug concentration on the intimal surface with 7 mN/mm<sup>2</sup> was increased as 10-30 times as other tension values. We found surface grooves in this case using an electron micrography. Therefore, we think that the drug delivery enhancement might be related to the groove formations of the vessel wall.
We studied heating drug delivery to vascular wall with Rhodamine B ranging 50 to 70°C ex vivo study. Porcine carotid artery was dipped in the heated Rhodamine B solution in 15 s and then cooled by 37°C saline. Rhodamine B concentration distribution in the vascular wall cross-section was measured by a fluorescence microscope using 550 nm for excitation and 620 nm emission for fluorescence detection. The total amount of measured fluorescence in the vascular wall was calculated as a indication of delivered Rhodamine B quantity. The delivered Rhodamine B quantity was increased with increasing heating temperature with 50 to 70°C. In the cases of 60 to 70°C heating, the delivered Rhodamine B quantity was 3.1 to 23.3 fold by that of 37°C. Defined penetration depth of the delivered Rhodamine B in the vascular wall was also significantly increased with 65°C and 70°C heating. We also studied heating drug delivery to the vascular wall with fluorescence labeled Paclitaxel with 70°C in 15 s and 60 s heating ex vivo. In both contact duration, the delivered Paclitaxel quantity was increased. To understand these drug delivery enhancement effects, we investigated the vascular cross-sectional structure change by the heating. Some holes over 50 nm in diameter appeared on the internal elastic lamina with 70°C heating. We prospected that vascular surface structure change by the heating might enhance drug delivery to the vascular wall.