Puerarin-Loaded Liposomes Co-Modified by Ischemic Myocardium-Targeting Peptide and Triphenylphosphonium Cations Ameliorate Myocardial Ischemia-Reperfusion Injury.

Autor:	Wang Y; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China., Li F; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China., Wei S; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China., Li W; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China., Wu J; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China., Li S; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China., Hu X; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China., Tang T; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China., Liu X; Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.; Institution of Clinical Pharmacy, Central South University, Changsha, People's Republic of China.
Jazyk:	angličtina
Zdroj:	International journal of nanomedicine [Int J Nanomedicine] 2024 Aug 07; Vol. 19, pp. 7997-8014. Date of Electronic Publication: 2024 Aug 07 (Print Publication: 2024).
DOI:	10.2147/IJN.S468394
Abstrakt:	Purpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury. Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury. Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size. Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury. Competing Interests: The authors declared no conflicts of interest in this work. (© 2024 Wang et al.)
Databáze:	MEDLINE
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