Title: Thermosensitive heparin-Pluronic® copolymer as effective dual anticancer drugs delivery system for combination cancer therapy

Authors: Nhat-Anh N. Tong; Ngoc Quyen Tran; Xuan Thi Diem Trinh Nguyen; Van Du Cao; Thi Phuong Nguyen; Cuu Khoa Nguyen

Addresses: Institute of Research and Development, Duy Tan University, No. 182 Nguyen Van Linh st., Da Nang, Vietnam; Institute of Applied Materials Science, Vietnam Academy Science and Technology, No. 01 Mac Dinh Chi St., Ho Chi Minh, Vietnam ' Institute of Research and Development, Duy Tan University, No. 182 Nguyen Van Linh st., Da Nang, Vietnam; Institute of Applied Materials Science, Vietnam Academy Science and Technology, No. 01 Mac Dinh Chi St., Ho Chi Minh, Vietnam ' School of Applied Chemistry, Tra Vinh University, No. 126 Nguyen Thien Thanh, Ward 5, Tra Vinh Province, Vietnam ' Faculty of Pharmacy, Lac Hong University, No. 10 Huynh Van Nghest., Dong nai Province, Vietnam ' Institute of Applied Materials Science, Vietnam Academy Science and Technology, No. 01 Mac Dinh Chi St., Ho Chi Minh, Vietnam ' Institute of Applied Materials Science, Vietnam Academy Science and Technology, No. 01 Mac Dinh Chi St., Ho Chi Minh, Vietnam

Abstract: In recent years, cancer therapy regimens combining dual drugs have proved their effectiveness in comparison with single drug. To increase efficacy of these anticancer drugs, an emerging approach involving the development of nanocarriers for dual anticancer drugs delivery has recently received much attention. In the study, thermosensitive Pluronic®-conjugated heparin was prepared to encapsulate and control the delivery of aquated cisplatin (CDDP) and 5-fluorouracil (5-FU) chemotherapeutic agents. The drug delivery system was determined to be in the size range of 80-100 nm by TEM and 260 nm by DLS. Formation of the complex was confirmed by 1H-NMR and FT-IR. The nanocomplexes exhibited high drug loading capacity (approximately 9.01% wt/wt of CDDP and 88.24% wt/wt of 5-FU). In vitro, drug-loaded nanogels showed slow and sustained release of the drugs over a long period of time at physiological pH and body temperature. Moreover, the cytotoxicity assay results also indicated that Hep-F127 was cytocompatible. Meanwhile, CDDP-5FU-Hep-F127 nanocomplexes show a significantly inhibited NCI-H460 lung cancer cell growth with the IC50 1.23 ± 0.07 µg/mL. The in vitro preliminary results indicate that the Hep-F127 nanocomplex is a candidate for suitable CDDP and 5-FU delivery which can be studied further in cancer therapy.

Keywords: thermosensitive nanogels; combination cancer therapy; delivery of dual anticancer drugs; cisplatin (CDDP); 5-fluorouracil (5-FU).

DOI: 10.1504/IJNT.2018.089566

International Journal of Nanotechnology, 2018 Vol.15 No.1/2/3, pp.174 - 187

Available online: 23 Jan 2018 *

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