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Nanostructured Lipid Carriers as Multifunctional Nanomedicine Platform for Pulmonary Co-Delivery of Anticancer Drugs and siRNA

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dc.creator Taratula, Oleh
dc.creator Kuzmov, Andriy
dc.creator Shah, Milin
dc.creator Garbuzenko, Olga B.
dc.creator Minko, Tamara
dc.date.accessioned 2013-05-14T21:49:03Z
dc.date.available 2013-05-14T21:49:03Z
dc.date.issued 2013-04-28
dc.identifier.citation Oleh Taratula, Andriy Kuzmov, Milin Shah, Olga B. Garbuzenko, and Tamara Minko. 2013. Nanostructured Lipid Carriers as Multifunctional Nanomedicine Platform for Pulmonary Co-Delivery of Anticancer Drugs and siRNA, Journal of Controlled Release, 171(3): 349-357. doi:10.1016/j.jconrel.2013.04.018 en_US
dc.identifier.uri http://hdl.handle.net/1957/38581
dc.description.abstract We developed, synthesized, and tested a multifunctional nanostructured lipid nanocarrier- based system (NLCS) for efficient delivery of an anticancer drug and siRNA directly into the lungs by inhalation. The system contains: (1) nanostructured lipid carriers (NLC); (2) anticancer drug (doxorubicin or paclitaxel); (3) siRNA targeted to MRP1 mRNA as a suppressor of pump drug resistance; (4) siRNA targeted to BCL2 mRNA as a suppressor of nonpump cellular resistance and (5) a modified synthetic analog of luteinizing hormone- releasing hormone (LHRH) as a targeting moiety specific to the receptors that are overexpressed in the plasma membrane of lung cancer cells. The NLCS was tested in vitro using human lung cancer cells and in vivo utilizing mouse orthotopic model of human lung cancer. After inhalation, the proposed NLCS effectively delivered its payload into lung cancer cells leaving healthy lung tissues intact and also significantly decreasing the exposure of healthy organs when compared with intravenous injection. The NLCS showed enhanced antitumor activity when compared with intravenous treatment. The data obtained demonstrated high efficiency of proposed NLCS for tumor-targeted local delivery by inhalation of anticancer drugs and mixture of siRNAs specifically to lung cancer cells and, as a result, efficient suppression of tumor growth and prevention of adverse side effects on healthy organs. en_US
dc.description.sponsorship This work was supported in part by grants from National Cancer Institute (R01 CA111766 and CA138533), National Institute of Environmental Health Sciences (R25 ES020721), National Science Foundation (CBET 0933966), and Department of Defense (W81XWH-10- 1-0347). en_US
dc.language.iso en_US en_US
dc.publisher Elsevier en_US
dc.relation.ispartofseries Journal of Controlled Release en_US
dc.relation.ispartofseries Vol. 171 no. 3 en_US
dc.subject Nanostructured lipid carrier en_US
dc.subject orthotopic lung cancer model en_US
dc.subject inhalation en_US
dc.subject luteinizing hormone-releasing hormone (LHRH) en_US
dc.subject imaging en_US
dc.subject drug resistance en_US
dc.title Nanostructured Lipid Carriers as Multifunctional Nanomedicine Platform for Pulmonary Co-Delivery of Anticancer Drugs and siRNA en_US
dc.type Article en_US
dc.description.peerreview yes en_US
dc.identifier.doi 10.1016/j.jconrel.2013.04.018


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