title: Paclitaxel-incorporated nanoparticles of hydrophobized polysaccharide and their antitumor activity.
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.
authors.affiliation: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Gun-Young
authors.initials: GY
authors.lastname: Hong
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Kang
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Oh
authors.forename: Chae-Eun
authors.initials: CE
authors.lastname: Song
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000089:Acetic Anhydrides / Q000737:chemistry; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D045744:Cell Line, Tumor; D011232:Chemical Precipitation; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005936:Glucans / Q000737:chemistry; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D010316:Particle Size; D011134:Polysaccharides / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000089:Acetic Anhydrides; D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D005936:Glucans; D011134:Polysaccharides; C031800:acetic anhydride; C009109:pullulan; D017239:Paclitaxel