| Autor: |
Dorostkar H; Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran., Haghiralsadat BF; Department of Advanced Medical Sciences and Technologies, Faculty of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran.; Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran., Hemati M; Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran.; Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran., Safari F; Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran.; Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran., Hassanpour A; Department of Anatomical Sciences, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran., Naghib SM; Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology and Biomaterials and Tissue Engineering Department, Breast Cancer Research Center, Motamed Cancer Institute, IUST, ACECR, Tehran 1684613114, Iran., Roozbahani MH; School of Advanced Technologies, Iran University of Science & Technology, Tehran 1684613114, Iran., Mozafari MR; Australasian Nanoscience and Nanotechnology Initiative (ANNI), Monash University LPO, Clayton, VIC 3168, Australia., Moradi A; Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 8916877391, Iran. |
| Abstrakt: |
Doxorubicin is one of the most effective chemotherapeutic agents; however, it has various side effects, such as cardiotoxicity. Therefore, novel methods are needed to reduce its adverse effects. Quercetin is a natural flavonoid with many biological activities. Liposomes are lipid-based carriers widely used in medicine for drug delivery. In this study, liposomal doxorubicin with favorable characteristics was designed and synthesized by the thin-film method, and its physicochemical properties were investigated by different laboratory techniques. Then, the impact of the carrier, empty liposomes, free doxorubicin, liposomal doxorubicin, and quercetin were analyzed in animal models. To evaluate the interventions, measurements of cardiac enzymes, oxidative stress and antioxidant markers, and protein expression were performed, as well as histopathological studies. Additionally, cytotoxicity assay and cellular uptake were carried out on H9c2 cells. The mean size of the designed liposomes was 98.8 nm, and the encapsulation efficiency (EE%) was about 85%. The designed liposomes were anionic and pH-sensitive and had a controlled release pattern with excellent stability. Co-administration of liposomal doxorubicin with free quercetin to rats led to decreased weight loss, creatine kinase (CK-MB), lactate dehydrogenase (LDH), and malondialdehyde (MDA), while it increased the activity of glutathione peroxidase, catalase, and superoxide dismutase enzymes in their left ventricles. Additionally, it changed the expression of NOX1, Rac1, Rac1-GTP, SIRT3, and Bcl-2 proteins, and caused tissue injury and cell cytotoxicity. Our data showed that interventions can increase antioxidant capacity, reduce oxidative stress and apoptosis in heart tissue, and lead to fewer complications. Overall, the use of liposomal doxorubicin alone or the co-administration of free doxorubicin with free quercetin showed promising results. |
