Journal
PROCESS BIOCHEMISTRY
Volume 84, Issue -, Pages 172-179Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.procbio.2019.06.013
Keywords
Doxorubicin; Sildenafil citrate; Cancer; Nanostructured lipid carriers; RGD
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Resistance to anticancer agents is considered as the main cause of chemotherapy failure. This study is aimed to prepare and optimize [Doxorubicin (Dox) + Sildenafil citrate (SC)]-coloaded Arginyl-glycyl-aspartic acid (RGD)-containing nanostructured lipid carriers (NLC-RGD) to overcome multidrug resistance limitation and improve cancer treatments. Consequently, [DOX + SC]-coloaded NLC-RGD were fabricated by homogenization method and characterized by several techniques. Then, cytotoxicity, cellular uptake, apoptosis, and expression level of some multi-drug resistance related genes were evaluated in [DOX + SC]-coloaded NLC-RGD treated cells. As results, particles with nano-size, narrow size distribution and suitable encapsulation efficiency (similar to 56% for DOX and similar to 81% for SC) were prepared. Our Results also demonstrated that co-delivery of DOX and SC by NLC-RGD promotes uptake and accumulation of drugs by integrin mediated endocytosis and possible ABC transporter inhibition. Cytotoxicity and apoptosis experiments revealed that co-delivery of DOX and SC by NLC-RGD is more effective approach for induction of apoptosis in comparison to individual treatment and delivery. Gene expression experiments revealed that SC reduces expression of ABCC1 and Nrf2. These findings indicated that NLC-RGD can be considered as an appropriate delivery system for co-delivery of DOX and SC to overcome DOX resistance to improve treatment efficacy in cancer.
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