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Novel Thermosensitive Polymer-Modified Liposomes as Nano-Carrier of Hydrophobic Antitumor Drugs

Abstract : Thermo-sensitive polymer-modified liposomes are able to achieve site-specific delivery of drugs. In this work, thermo-sensitive polymers were synthesized by atomic transfer radical polymerization of N-isopropyl acrylamide (NIPAAm) and N,N-dimethyl acrylamide (DMAAm) using bromoisobutyryl distearoyl phosphoethanolamine (DSPE-Br) as initiator. The resulting PNIPAAm-DSPE and P(NIPAAm-DMAAm)-DSPE polymers were characterized using proton nuclear magnetic resonance, Fourier transform infrared, and ultravioletevisible spectroscopy. PNIPAAm-DSPE and P(NIPAAm-DMAAm)-DSPE exhibit a lower critical solution temperature of 34.0 and 46.9 C in water, and 29.8 and 38.8 C in phosphate buffered saline, respectively. Paclitaxel-loaded thermo-sensitive liposomes were prepared using film hydration method, followed by post-insertion of P(NIPAAm-DMAAm)-DSPE into the liposome bilayer. Drug release of traditional and thermosensitive liposomes was comparatively studied at 37 and 40 C. The total release and release rate of thermosensitive liposomes at 40 C were much higher than those at 37 C. And drug release is higher for thermosensitive liposomes than for traditional liposomes because insertion of thermo-sensitive polymer chains affects the system's stability. MTT assay showed that thermosensitive liposomes present no cytotoxicity to L929 cells at the tested concentrations, and paclitaxelloaded liposomes have significant cytotoxicity against A549 cancer cells. Therefore, it is concluded that P(NIPAAm-DMAAm)-DSPE modified thermo-sensitive liposomes could be promising as nano-carrier of antitumor drugs.
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https://hal.archives-ouvertes.fr/hal-03093011
Contributor : Suming Li <>
Submitted on : Tuesday, January 5, 2021 - 6:12:15 PM
Last modification on : Friday, January 8, 2021 - 3:27:36 AM

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Laishun Xi, Chenglong Li, Yuandou Wang, Yanling Gong, Feng Su, et al.. Novel Thermosensitive Polymer-Modified Liposomes as Nano-Carrier of Hydrophobic Antitumor Drugs. Journal of Pharmaceutical Sciences, Wiley, 2020, 109 (8), pp.2544-2552. ⟨10.1016/j.xphs.2020.05.006⟩. ⟨hal-03093011⟩

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