Local Use of Hydrogel with Amiodarone in Cardiac Surgery: Experiment and Translation to the Clinic

Abstract

The objective of this study was to study the use of the hydrogel biopolymer based on sodium alginate (“Colegel”) with a drug substance—amiodarone—for the prevention of postoperative atrial fibrillation (POAF) in cardiac surgery. The experimental part of the study was performed on 46 rabbits. Five groups were formed: in the first group, the dose of amiodarone in hydrogel was 1 mg; in the second group—3 mg; in the third group—6 mg; in the fourth group, hydrogel was used without amiodarone; in the fifth group, 60 mg amiodarone was administered intravenously. The animals from each group were removed from the experiment for the pathomorphological study of the heart after 3, 7 and 14 days. The studied endpoints were: the heart rate control; the development of the blockades of the conduction system of the heart; and the development of inflammation according to laboratory pathomorphological studies. The translational clinical part involved a randomized clinical trial which included 60 patients, with an average age of 62 ± 8.5 years. All patients were randomized into two groups: the study group (n = 30, with the application of amiodarone hydrogel) and the control group (n = 30, without the application of amiodarone hydrogel). The dose of amiodarone in the hydrogel material was 60 mg for all patients. The heart rhythm was monitored during 5 days. The primary endpoint was the development of POAF. Secondary endpoints were: the dynamics of heart rate; the duration of the QT and PQ intervals; the development of blockades of the cardiac conduction system; as well as the dynamics of AST and ALT. According to the results of the experimental part, it was found that the method of the local epicardial delivery of amiodarone by the hydrogel material was safe. Hydrogel with amiodarone is effective for reducing the heart rate in the animal experiment in comparison to the control group and the group with the intravenous administration of the drug. The optimal dose of amiodarone in hydrogel was 1 mg per 1 kg. According to the results of the clinical part, it was found that the method of the local epicardial delivery of amiodarone as a hydrogel material proved its safety. Hydrogel with amiodarone at a dose of 60 mg was effective in preventing POAF in patients after coronary artery bypass grafting (CABG) operations in comparison to the control group (p < 0.001). The age and procedure of application of the amiodarone gel were significantly associated with POAF (p = 0.009 and p = 0.011, respectively). The use of hydrogel with amiodarone reduced the probability of developing POAF 18.9-fold. The method of the local epicardial delivery of amiodarone in the form of a hydrogel material is safe. The use of hydrogel with amiodarone after CABG reduced the probability of developing POAF.

Application of 3D Bioprinting in Urology

“…Its 3D structure and biophysical properties (shape, mechanical strength and permeability) are similar to naturally sourced ECM [ 47 ]. It is currently extensively used in the medical field with 3D bioprinting, including the repair of skin wounds [ 48 , 49 , 50 ], bone damage [ 51 , 52 , 53 ], cartilage injury [ 54 , 55 , 56 ] and cardiac rehabilitation [ 57 , 58 , 59 , 60 ].…”

Cardiac-Targeting Peptide: From Discovery to Applications

“…It is increasingly being recognized that designing new drugs is not enough; they have to be delivered to a specific organ, and preferably to the cells of interest. In the context of targeting the heart, the strategies have ranged from physical approaches ranging from direct microneedle injections into the myocardium [12,13], intra-coronary instillation [13], retrograde perfusion of the coronary sinus [14,15], and placement of hydrogels into the pericardial space [16][17][18][19]. On the vector side, viral vectors have ranged from adenovirus [20,21], lentivirus [22], adeno-associated viruses [23,24], or non-viral vectors comprising exosomes [25], nanoparticles [26,27] or microbubbles targeted to the heart by destruction of these bubbles with ultrasound during their passage through the heart under direct visualization [28][29][30].…”

Designing Microneedle Patch for Prophylaxis of Postoperative Atrial Fibrillation

“…To address this, some localized drug delivery strategies have been explored for targeted delivery of amiodarone directly to the atria. , For example, epicardial applications of amiodarone-releasing hydrogels have been proved safe and effective for prophylaxis of POAF in patients after coronary artery bypass grafting surgery, by enhancing drug accumulation in the atrial tissue while minimizing that in off-target tissues. − However, some limitations still remain, such as a short release duration (less than 30 days), unsatisfactory tissue penetration efficiency, and requirement of a sewing procedure for tissue fixation. Polymeric microneedles (MNs) have emerged as minimally invasive and effective tools for transdermal or localized drug delivery to specific tissues. − However, due to the small sizes of MNs, a major drawback of MN delivery systems is their limited drug loading capacity, generally giving a release duration of several days or hours.…”