Catheter ablation has emerged as an effective alternative for the treatment of atrial fibrillation (AF). Radiofrequency energy is used to make local myocardium necrotic and achieve electrical isolation of pulmonary veins. Local ablation damage to the myocardium will lead to obvious hematoma and inflammation of the tissues that surrounds the ablation sites, triggering inflammatory cell infiltration and inflammatory cytokine release. This may lead to early recurrence of atrial fibrillation.

“Early recurrence after the ablation procedure may relate to localized edema and inflammation due to ablation damage to local myocardium. It can be highly symptomatic and will be frustrating to both patient and electrophysiologist who perform the procedure,” said Xiaoqing Liu associate chief physician from Beijing Chaoyang Hospital, “Local edema and inflammation caused by ablation energy are inevitable, but there is no effective method to treat it.”

Theoretically, the most direct way to reduce perioperative inflammation is to use glucocorticoids. However, the systemic application of glucocorticoids must reach a certain threshold in order to reach the ablation site and reduce local inflammation, which may lead to the side effects related to glucocorticoid overuse. Budesonide (BUD) is classic anti-inflammatory drug, a potent glucocorticoid, widely used in the treatment of respiratory diseases and inflammatory bowel disease with little whole-body side effects. But due to its low water-solubility, budesonide can not be used intravenously.

“Nanotechnology is particularly useful in solving this conundrum,” said Zhou Li, “FDA-approved PLGA has been applied to injectable drug subsidiaries due to its biodegradable and biocompatible characteristics, a classic nanoparticle which can not only improve the stability of drugs in the solution but also improve the pharmacokinetics.”

We designed a PLGA nanoparticle internally loaded with BUD (P/B NPs) and crosslinked with chitosan oligosaccharide (P/B-COS NPs). This compound converted BUD into nanoparticles of 200 nm which were able to form stable solution in natural saline.

The study was published (May. 31) in Research, the first Science Partner Journal recently launched by the American Association for the Advancement of Science (AAAS) in collaboration with the China Association for Science and Technology (CAST). Xiaoqing Liu is an associate chief physician in cardiology from Beijing Chaoyang Hospital and Zhou Li is a full Professor in Beijing Institute of Nanoenergy and Nanosystems and School of Nanoscience and Technology, University of Chinese Academy of Sciences.

During the ablation process, these P/B-COS NPs will be delivered directly to the local myocardium with irrigation from the catheter tip. The heat generated during ablation rendered those particles rupture and released budesonide ingredient, which produce immediate anti-inflammatory effects. Another number of intact particles would also enter local tissues and continued to have anti-inflammatory effects in the following days. All these would ameliorate myocardial inflammation and edema.

“Budesonide has a high first-pass effect, remaining particles that entered the blood stream will be cleared in short time,” said Xiaoqing Liu.

“Catheter ablation with irrigation of P/B-COS NPs solution in saline has not only proved the feasibility of transforming a glucocorticoid from liposolubility to water-solubility, and also presented a new way of local delivery of medication with irrigation catheter,” said Zhou Li. This may not only be a brand-new method of enhancing ablation effect, but also become a new way of medication administration to treat other diseases.

Source: https://spj.sciencemag.org/journals/research/2022/9816234/

Tag: Health Science