کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2153342 | 1090170 | 2016 | 7 صفحه PDF | دانلود رایگان |
IntroductionAlthough liposomes hold promise for cancer therapy, the effectiveness of treating myocardial ischemia by promoting angiogenesis has yet to be proved. Nanoliposomes loaded with therapeutic agents can effectively target ischemic myocardium via enhanced permeability and retention. Surface polyethylene glycol (PEG) modification can further facilitate effective targeting by prolonging liposomal circulation. This study aimed to determine whether PEGylated nanoliposomes are effective in facilitating targeted drug delivery and treating myocardial ischemia.MethodsRats subjected to 30 min of myocardial ischemia were given 99mTc-hexamethylpropyleneamine oxime- or 99mTc-diethylenetriamine pentaacetate-labeled liposomes with mean diameters of ~ 100 nm or ~ 600 nm with or without PEG modifications to determine the extent of myocardial uptake in the different conditions. Therapeutic effectiveness was assessed by studying changes in myocardial perfusion defects with 99mTc-tetrofosmin autoradiography and vascular density with immunohistochemistry at 7 days post-treatment.ResultsThe liver and spleen showed the largest capacity for liposome uptake. Uptake by the liver and spleen was more pronounced when the liposomes were larger. Conversely, myocardial liposome uptake was significantly greater when the liposomes were ~ 100 nm rather than ~ 600 nm in diameter. Surface modification with PEG significantly augmented myocardial uptake of ~ 100 nm liposomes. PEG modification did not affect the size dependence. To investigate therapeutic efficacy, hearts subjected to ischemia received PEGylated nanoliposomes encapsulated with angiogenic peptides. Our data demonstrated that PEGylated nanoliposomes loaded with angiogenic peptides improved myocardial perfusion defects and increased vascular density. A 10-fold increase in liposomal concentration did not further benefit myocardial ischemia.ConclusionsLiposomal angiogenic formulation with size control and PEG modification may be effective treatment strategy for myocardial ischemia. Increasing the concentration of liposomes does not necessarily benefit myocardial ischemia.
Journal: Nuclear Medicine and Biology - Volume 43, Issue 9, September 2016, Pages 552–558