Abstract
OBJECTIVE: This study aims to design and fabricate a leadless pacemaker (LPM) electrode loaded with rapamycin (RAPA)-poly(lactic-co-glycolic acid) (PLGA) drug sustained-release system to reduce the local fibrous tissue proliferation after LPM implantation, reduce local bioelectrical impedance, and facilitate the safe extraction of LPM after use. METHODS: We fabricated an LPM electrode loaded with the RAPA-PLGA drug-sustained-release system and carried out in vitro and in vivo experiments to verify its effect. RESULTS: A scanning electron microscope showed that the LPM electrode cavity was loaded with the RAPA-PLGA drug's sustained-release system. The energy-dispersive spectrometer showed that the LPM electrode had RAPA and PLGA-related elements. The average drug loading rate of the drug sustained-release system was (51.02% ± 2.66) %, and the encapsulation rate was (85.04% ± 4.43%). The RAPA loaded in the electrode chamber was about (337.83 ± 53.66)μg. In vitro release results show that the LPM electrode loaded with RAPA-PLGA can continue to release for 44 days. In vitro cell inhibition experiments showed that the drug-loaded electrode group had an obvious inhibitory effect on fibroblasts, and the difference between the groups was significant (p < 0.05). In vivo experiments showed that the local bioelectrical impedance of the drug-loaded electrode group is lower than that of the control group, with a difference between groups with statistical significance (p < 0.05). The histopathological analysis of tissue sections from the site of (LPM electrode implantation revealed reduced fibrous tissue hyperplasia in the drug-loaded electrode group compared to the control group. Additionally, H&E staining indicated that the implantation of drug-loaded electrodes did not induce abnormal alterations in the liver, heart, spleen, lung, or kidney tissues. CONCLUSION: The LPM electrode loaded with RAPA-PLGA demonstrates significant, sustained drug release and anti-proliferative effects in vitro. This drug-loaded electrode has been deemed safe for implantation in animal models. It can effectively inhibit local fibrous tissue proliferation and reduce local bioelectrical impedance, offering a technical strategy to prolong the in vivo functionality of LPMs and enhance clinical procedures.