A platelet-cloaking tetramethylprazine-loaded microemulsion for improved therapy of myocardial ischaemia/reperfusion injury

Abstract

Myocardial ischaemia-reperfusion injury (MI/RI) induces injury against cardiomyocytes and triggers myocardial infarction. Previously, we demonstrated that tetramethylprazine (TMP) was a promising therapeutic agent for attenuating MI/RI. However, poor absorption and low homing efficiency are two main obstacles to the further application of TMP. In this study, a platelet membrane-cloaking TMP-loaded microemulsion (P/TMP-MEs) capable of promoting in vivo absorption and decreasing non-targeted accumulation was fabricated for the improved MI/RI therapy. The average particle size and zeta potential of P/TMP-MEs were 35.9 ± 2.5 nm and −29.4 ± 3.1 mV, respectively. 35.4 ± 2.4 wt% TMP was released from P/TMP-MEs after 48 h of incubation with rat plasma. The coating of the platelet membrane significantly decreased the internalisation of P/TMP-MEs by THP-1 macrophage-like cells compared with the non-platelet modified TMP-loaded microemulsion (TMP-MEs). Besides, P/TMP-MEs did not activate the complement system. After treatment with P/TMP-MEs, the dehydrogenase (LDH) level of the cardiomyocytes was significantly lower than other controls. Rats single-administrated with P/TMP-MEs exhibited the area under the plasma concentration-time curve (AUC) at 463796.7 ± 53614.3 ng/mL/h, and ∼400 ng/mL TMP could still be detected from the plasma after 24 h of administration, exhibiting a prolonged blood circulation time as the platelet membrane coating. More importantly, in the MI/RI therapy in vivo, the creatine kinase (CK) and LDH of the rats treated with P/TMP-MEs were remarkably decreased compared with the free TMP and TMP-MEs groups. The combinational strategy of platelet membrane coating and microemulsion assembly endows TMP with a better prospect for MI/RI therapy.

Keywords:

• Tetramethylprazine
• myocardial ischaemia/reperfusion injury
• platelet-cloaking
• microemulsion
• drug delivery

Author contributions

Zhi Zuo and Menghuan Li designed the research. Zhi Zuo, Menghuan Li, Tao Han, Xuhui Zheng, Wenming Yao, and Hui Wang carried out the experiments and data analysis. Zhi Zuo wrote the manuscript. Zhi Zuo, Xinli Li, and Ding Qu revised the manuscript. All of the authors have read and approved the final manuscript.

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This work was financially supported by Nanjing Science and Technology Innovation Projects for Overseas Graduates.