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Abstract

In the study, a thermosensitive pluronic-conjugated heparin (Hep-F127) was prepared in order to encapsulate and control delivery of the hydrolyzed Cisplatin (CDDP) and 5-Fluorouracil (5-FU) chemotherapeutic agents in order to increase pharmacokinetic tolerance and antitumor activity of the anticancer drugs due to synergistic effects of the drugs combined with the characteristic of the delivery nanosystems. Heparin (Sulfated polysaccharides) takes advantage forming complex with the activated species of CDDP via conjugation with the carboxyl and sulfate groups of heparin. Among the various amphiphilic block copolymers, Pluronic F127 consist of poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO) that self-assemble in aqueous solution to form micelle structure which could encapsulate 5-FU, hydrophobic anticancer drugs, via hydrophobic interaction in the range of body temperature. Formation of the complex in the system was confirmed by 1H-NMR and FT-IR. The drugs delivery system was formulated in the range of 80-100 nm by TEM, 260 nm by DLS and exhibited high drug loading capacity (approximately 45% wt/wt of CDDP and 88.24% wt/wt of 5-FU). In vitro, drug-loaded nanogels showed a slow and sustained release of the drugs over a long period time in physiological pH at body temperature. Moreover, the cytotoxicity assay results also indicated that Hep-F127 was cytocompatible; meanwhile, drug-loaded nanogels show a significantly inhibited NCI-H460 lung cancer cell growth with IC50 at 1.23�±0.07 �¼g/mL. The in vitro preliminarily obtained results indicate that the Hep-F127 nanocomplex could be a candidate for suitable CDDP and 5-FU delivery which can be studied further in cancer therapy. The antitumor activity of the drug delivery system is conducting on xenograft model.

Biography

Email: tnquyen@iams.vast.vn tongnguyennhatanh@gmail.com