In Vitro Determination of Drug Transfer from Drug-Coated Balloons

Abstract

Drug-coated balloons are medical devices designed to locally deliver drug to diseased segments of the vessel wall. For these dosage forms, drug transfer to the vessel wall needs to be examined in detail, since drug released into the blood is cleared from the site. In order to examine drug transfer, a new in vitro setup was developed combining the estimation of drug loss during advancement to the site of application in a model coronary artery pathway with a hydrogel compartment representing, as a very simplified model, the vessel wall. The transfer of fluorescent model substances as well as the drug paclitaxel from coated balloons to the simulated vessel wall was evaluated using this method. The model was suitable to quantify the fractions transferred to the hydrogel and also to qualitatively assess distribution patterns in the hydrogel film. In the case of fluorescein sodium, rhodamin b and paclitaxel, vast amounts of the coated substance were lost during the simulated passage and only very small fractions of about 1% of the total load were transferred to the gel. This must be attributed to good water solubility of the fluorescent substances and the mechanical instability of the paclitaxel coating. Transfer of the hydrophobic model substance triamterene was however nearly unaffected by the preliminary tracking procedure with transferred fractions ranging from 8% to 14%. Analysis of model substance distribution yielded inhomogeneous distributions indicating that the coating was not evenly distributed on the balloon surface and that a great fraction of the coating liquid did not penetrate the folds of the balloon. This finding is contradictory to the generally accepted assumption of a drug depot inside the folds and emphasizes the necessity to thoroughly characterize in vitro performance of drug-coated balloons to support the very promising clinical data.

Necrotic leg ulcers secondary to hydrophilic polymer gel emboli

“…Advancement in revascularization procedures performed by vascular surgeons during the last 20 years has played a significant role in management of the most severe form of peripheral artery disease, including critical limb ischemia and tissue necrosis 10 . The addition of hydrophilic polymer coatings to the surfaces of catheters, stents, balloons, guidewires, and other revascularization devices decreases the coefficient of friction, which therefore allows for easier passage and less vessel spasm through narrow vascular spaces 11, 12, 13, 14. Similar devices are used by interventional cardiologists and radiologists, neurosurgeons, and nephrologists in addition to other subspecialists in the revascularization and repair of vessels of the lungs, heart, brain, and kidneys 14, 15, 16, 17.…”

Usage of different vessel models in a flow-through cell: in vitro study of a novel coated balloon catheter

“…Seidlitz et al used pure PTX-coated balloons and showed PTX transfer rates to gel below 1% (calcium alginate as vessel model). 12 In their study, they also used a model of a coronary artery pathway to investigate drug loss and drug transfer to the gel. However, in our study with the novel DCB coating more PTX was delivered upon dilation (calcium alginate: 6.4 AE 3.8% compared to below 1%).…”

“…9 To date, there are only a few in vitro studies presented, characterizing and describing the simulated use of drug coated balloon catheters in an in vitro vessel model. [10][11][12] The previously used models are far from physiological properties of the material, e.g. a silicone tube acts like an artery.…”

Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons

“…The excipient enhances the adhesion of the drug to the balloon surface, increases the stability of the drug coating during handling and delivery, and maximizes drug retention to the targeted arterial segment. [18][19][20][21][22][23][24] Current DCBs excipients include polysorbate and sorbitol, urea, polyethylene glycol (PEG) and butyryl-tri-hexyl citrate (BTHC). The rationale for the selection of these various excipients varies.…”