Baicalin-loaded Polydopamine modified ZIF-8 NPs inhibits myocardial ischemia/reperfusion injury in rats

Abstract

Baicalin (BAN) has shown promise in alleviating myocardial ischemia/reperfusion (I/R) injury, yet its limited solubility and biocompatibility have hindered its application. Developing drug delivery systems is a promising strategy to enhance the therapeutic potential of BAN in the context of I/R injury. This study aims to prepare a BAN-loaded nanodrug system using polydopamine (PDA)-modified Zeolitic imidazolate framework-8 (ZIF-8) as a carrier, with the goal of improving BAN's mitigating effects on I/R injury. We prepared the BAN nanoparticles (NPs) system, PZB NPs, using ZIF-8 as the carrier. The system was characterized in terms of morphology, particle size, zeta potential, and X-ray diffraction (XRD). We assessed the cytotoxicity of PZB NPs in H9c2 cells, investigated its effects and mechanisms in H/R-induced H9c2 cells, and evaluated its ability to alleviate myocardial I/R injury in rats. PZB NPs exhibited good dispersion, with a BAN loading efficiency of 26.43 ± 1.55%, a hydrated particle size of 102.21 ± 1.19 nm, and a zeta potential of −24.84 ± 0.07 mV. It displayed slow and sustained drug release in an acidic environment (pH 5.5). In vitro studies revealed that PZB NPs was non-cytotoxic and significantly enhanced the recovery of H/R injury H9c2 cell viability. PZB NPs suppressed cell apoptosis, activated the Nrf2/HO-1 pathway, and cleared ROS. In vivo study demonstrated that PZB NPs significantly reduced infarct size, ameliorated fibrosis and improved heart function. The PZB NPs markedly enhances BAN's ability to alleviate I/R injury, both in vitro and in vivo, offering a promising drug delivery system for clinical applications.

Keywords:

• Myocardial ischemia/reperfusion injury
• polydopamine
• ZIF-8
• baicalin
• Nrf2
• HO-1

CRediT authorship contribution statement

Changgong Chen: Conceptualization, Methodology, Writing- Original draft preparation.Wenhua Liu: Methodology, Data curation, Writing- Original draft preparation. Xingjian Gu: Investigation, Visualization. Li Zhang: Investigation, Visualization. Xiang Mao: Software, Validation. Zili Chen: Investigation, Writing- Original draft preparation. Luyuan Tao: Resources, Supervision and Writing- Reviewing and Editing.

Disclosure statement

The authors declared that they have no competing interests.

Ethic statement

Ethical approval for this study was obtained from the Wenzhou Medical University’s Animal Research Committee (wydw 2023-0092).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by Scientific Research Foundation of the Science and Technology Department of Taizhou City (No. 20ywa41).