International Journal of Pharmaceutics 2012-08-20

Paclitaxel-incorporated nanoparticles of hydrophobized polysaccharide and their antitumor activity

Sang Joon Lee, Gun-Young Hong, Young-Il Jeong, Mi-Sun Kang, Jong-Suk Oh, Chae-Eun Song, Hyun Chul Lee, Sang Joon Lee, Gun-Young Hong, Young-Il Jeong, Mi-Sun Kang, Jong-Suk Oh, Chae-Eun Song, Hyun Chul Lee

Index: Int. J. Pharm. 433(1-2) , 121-8, (2012)

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Abstract

The aim of this study was to characterize paclitaxel-incorporated polysaccharide nanoparticles and evaluate their antitumor activity in vitro and in vivo. Pullulan was hydrophobically modified using acetic anhydride to make the paclitaxel-incorporated nanoparticles. Pullulan acetate (PA) was used to encapsulate paclitaxel using the nanoprecipitation method. The particles had spherical shapes under electron microscopy with sizes <100 nm. The sizes of paclitaxel-incorporated nanoparticles increased to >100 nm, and higher drug feeding induced higher particle size and drug content. Initial drug burst release was observed until 2 days and then the drug was continuously released over 1 week. Intrinsic cytotoxicity of empty PA nanoparticles was tested with RAW264.7 macrophage cells for biocompatibilty. The viability of RAW264.7 cells was >93% at all concentrations of empty PA nanoparticles, indicating that the PA nanoparticles are not acutely cytotoxic to normal human cells. The nanoparticles showed lower antitumor activity in vitro against HCT116 human colon carcinoma cells than that of paclitaxel itself, indicating the sustained release properties of nanoparticles. An in vivo study using HCT116 human colon carcinoma-bearing mice showed that paclitaxel-incorporated PA nanoparticles reduced tumor growth more than that of paclitaxel itself. These results indicate that PA paclitaxel-incorporated nanoparticles are a promising candidate for antitumor drug delivery.Copyright © 2012 Elsevier B.V. All rights reserved.