We studied the dependence of a perpendicular pressure to the luminal surface on the heating drug delivery performance using a laser-mediated thermal balloon with porcine carotid artery walls ex vivo. We proposed the combination use of our laser-mediated thermal balloon and drug coated balloon (DCB) to enhance a drug delivery performance. We prospected that the perpendicular pressure, which was applied directly to the luminal surface by balloon dilatation, would enhance the quantity of DCB drug delivered into artery wall. To simulate our laser thermal balloon heating, 63°C preheated artery samples were prepared by heated saline dropping for 15 s, and then these samples were dipped in 37°C saline for 15 s. Non-heated artery samples were prepared by dipping in 37°C saline for 30 s. The perpendicular pressure up to 10 atm corresponding to DCB dilatation pressure was added directly to these artery samples by fluorescence Rhodamine B solution for 30 s. The quantity of drug delivered was microscopically measured with fluorescence brightness in the cross-section of the drug delivered artery samples. We found drastic drug delivery increase at 8 atm using the pre-heated artery sample. Delamination of intima layer was observed by EVG stained cross-sectional specimens with 8 atm in the pre-heated artery sample. We think this drastic pressure dependence on the heating drug delivery performance might be corresponding to increase in permeability of drug into the artery wall originated to morphology change in intima.
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/mm2 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/mm2 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/mm2. 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/mm2 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/mm2 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.
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