title: Preparation, physical characterization and pharmacokinetic study of paclitaxel nanocrystals.
abstract: Paclitaxel (PTX) is a natural broad-spectrum anticancer drug with poor aqueous solubility. PTX nanocrystals were formulated to improve the water solubility, and PTX nanosuspensions were prepared using anti-solvent precipitation, and then organic solvent and surfactants were removed by filtering through a vacuum system. The physical characterization of PTX nanocrystals were measured by transmission electron microscope, X-ray diffraction and differential scanning calorimetry. In addition, saturation solubility, in vitro release, stability and pharmacokinetic characteristics were examined. The average particle size of PTX nanocrystals was ∼200 nm, and they had a stable potential and a uniform distribution. Paclitaxel nanocrystals can effectively improve drug solubility and in vitro release. PTX pharmacokinetic and tissue distribution studies were compared after intravenous administration of nanocrystals versus a commercial injection formulation. PTX nanocrystals were rapidly distributed with a longer elimination phase. Moreover, tissue distribution indicated that PTX nanocrystals are mainly absorbed by the liver and spleen and may offer reduced renal and cardiovascular toxicity which may reduce side effects.
authors.affiliation: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology , Beijing , P.R. China .
authors.forename: Lisha
authors.initials: L
authors.lastname: Wei
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Zhenqiao
authors.initials: Z
authors.lastname: Kang
authors.forename: Meng
authors.initials: M
authors.lastname: Meng
authors.forename: Aiping
authors.initials: A
authors.lastname: Zheng
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianxu
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005260:Female; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism*; D017239:Paclitaxel / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D010316:Particle Size; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D014961:X-Ray Diffraction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
keywords: Nanocrystals; X-ray diffraction; paclitaxel; pharmacokinetics; tissue distribution