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. 2020 Aug;109(8):2544-2552.
doi: 10.1016/j.xphs.2020.05.006. Epub 2020 May 21.

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

Laishun Xi  1 , Chenglong Li  1 , Yuandou Wang  2 , Yanling Gong  3 , Feng Su  4 , Suming Li  5
Affiliations

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

Laishun Xi et al. J Pharm Sci. 2020 Aug.

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 ultraviolet-visible 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 thermo-sensitive liposomes present no cytotoxicity to L929 cells at the tested concentrations, and paclitaxel-loaded 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.

Keywords: Biocompatibility; Cancer chemotherapy; Controlled release; Liposome; Polymeric drug carrier; Poorly water-soluble drug.

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