期刊
DRUG DELIVERY
卷 27, 期 1, 页码 599-606出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2020.1754525
关键词
Myocardium delivery; liposomes; TAT; PCM; red cell membrane
资金
- National Natural Science Foundation of China [81400212]
- Chongqing Basic and Frontier Research Project [CSTC2018jcyjAX0126]
- Chongqing Teenagers Innovative Talent Training Program [CY190401]
Ischemic cardiac disease (ICD) is a cardiovascular disease with high morbidity and mortality. In this study, a novel myocardial targeted drug delivery system was developed represented by co-modified liposomes consisting of red cell membrane (RCM), and the peptides TAT and PCM. Liposomes were prepared using a membrane dispersion-ultrasonic method; the prepared 1% TAT and 3% PCM micelles were mixed with liposomes and under overnight stirring to form polypeptid-modified liposomes. RCM was isolated from mice blood, and the mechanical force facilitated RCM adhesion to the lipid bilayer. The characteristics of liposomes such as the morphology, particle size, zeta-potential, and RCM-conjugation to lipsomes were evaluated. Uptake efficiency and cellular toxicity of liposomes were evaluated in vitro on myocardial cells (MCs). As regard the experiments in vivo, liposomes were intravenously injected into mice, and the blood and organs were collectedat different times to analyze the pharmacokinetics profile of liposomes. The cellular uptake and intracellular distribution of liposomes of different composition into MCs demonstrated that RCM-modified liposomes had the best delivery capability. The pharmacokinetics study further demonstrated that RCM-modified liposomes had prolonged mean residence time (MRT) and more accumulation in the heart. This study indicated that RCM can be used to modify liposomes in combination with polypeptides, because such modification increases the myocardial targeting of liposomes. Therefore, this system constructed in this study might be a potentially effective myocardial drug delivery system.
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