Thermosensitive Nanogels Based Heparin-Pluronic For Enhancing Anticancer Drug Cisplatin Loading And Releasing Efficiency Against Lung Cancer Cell

Abstract

Thermosensitive pluronic copolymer was conjugated to sulfated polysaccharides (Heparin) to form platforms which can complex with the hydrolyzed Cisplatin (CDDP) via conjugation with the carboxyl and sulfate groups. Moreover, poly(ethylene oxide) – poly(propylene oxide) – poly(ethylene oxide) (PEO–PPO–PEO) block copolymers, Pluronic F127 (F127) with thermal response and hydrophobic domand (-PPO-) was able to package a certain amount of CDDP via hydrophobic interaction when the solution was heated over 32oC. Modified polymers, obtained heparin-pluronic copolymer, Heparin-pluronic nanogels carrying CDDP were characterized by Proton nuclear magnetic resonance spectroscopy (1H-NMR), Fourier transform infrared spectra (FT-IR), Transmission electron microscopy (TEM). The content of loaded CDDP was measured by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES: AOAC official method 965.09). Heparin-pluronic nanocomplex are formulated with a controllable size (in the range of 20-60nm) and high drug loading capacity (approximately 42.5% wt/wt at 37oC and 37.5% wt/wt at 25oC). In vitro cytotoxicity study, the heparin-conjugated pluronic nanogel was cytocompatible and CDDP drug was highly cytotoxic. However, CDDP-loaded nanocomplex can reduce the cytotoxic ability of free CDDP, which still maintain a significantly anti-proliferative activity on cancer cells. The in vitro preliminary obtained results indicates that the nanogel is a suitable CDDP delivery candidate for delivering CDDP and other hydrophobic drugs which can be used in cancer treatments and other biomedical applications. Keywords: Thermosensitive nanogel/ nanoparticle Sulfated polysaccharides (Heparin) Cisplatin (CDDP) Hydrolyzed cisplatin Pluronic