title: Nanoparticulated docetaxel exerts enhanced anticancer efficacy and overcomes existing limitations of traditional drugs.
abstract: Nanoparticulation of insoluble drugs improves dissolution rate, resulting in increased bioavailability that leads to increased stability, better efficacy, and reduced toxicity of drugs. Docetaxel (DTX), under the trade name Taxotere™, is one of the representative anticancer chemotherapeutic agents of this era. However, this highly lipophilic and insoluble drug has many adverse effects. Our novel and widely applicable nanoparticulation using fat and supercritical fluid (NUFS™) technology enabled successful nanoscale particulation of DTX (Nufs-DTX). Nufs-DTX showed enhanced dissolution rate and increased aqueous stability in water. After confirming the preserved mechanism of action of DTX, which targets microtubules, we showed that Nufs-DTX exhibited similar effects in proliferation and clonogenic assays using A549 cells. Interestingly, we observed that Nufs-DTX had a greater in vivo tumor growth delay effect on an A549 xenograft model than Taxotere™, which was in agreement with the improved drug accumulation in tumors according to the biodistribution result, and was caused by the enhanced permeability and retention (EPR) effect. Although both Nufs-DTX and Taxotere™ showed negative results for our administration dose in the hematologic toxicity test, Nufs-DTX showed much less toxicity than Taxotere™ in edema, paralysis, and paw-withdrawal latency on a hot plate analysis that are regarded as indicators of fluid retention, peripheral neuropathy, and thermal threshold, respectively, for toxicological tests. In summary, compared with Taxotere™, Nufs-DTX, which was generated by our new platform technology using lipid, supercritical fluid, and carbon dioxide (CO2), maintained its biochemical properties as a cytotoxic agent and had better tumor targeting ability, better in vivo therapeutic effect, and less toxicity, thereby overcoming the current hurdles of traditional drugs.
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea ; Asan Institute for Life Sciences, Duksung Women's University, Seoul, South Korea.
authors.forename: Jinhyang
authors.initials: J
authors.lastname: Choi
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Ko
authors.affiliation: Center for Development and Commercialization of Anti-cancer Therapeutics, Duksung Women's University, Seoul, South Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Chung
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Ju
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul, South Korea.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Lim
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea.
authors.forename: Intae
authors.initials: I
authors.lastname: Park
authors.affiliation: Bio-Synectics, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Kab-Sig
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Bio-Synectics, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Joo-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea ; Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea ; College of Pharmacy, Duksung Women's University, Seoul, South Korea.
authors.forename: Joohee
authors.initials: J
authors.lastname: Jung
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea ; Asan Institute for Life Sciences, Duksung Women's University, Seoul, South Korea.
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea ; Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Si Yeol
authors.initials: SY
authors.lastname: Song
authors.affiliation: Institute for Innovative Cancer Research, Duksung Women's University, Seoul, South Korea ; Center for Development and Commercialization of Anti-cancer Therapeutics, Duksung Women's University, Seoul, South Korea ; Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008870:Microtubules; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel
keywords: Nufs-DTX; anticancer efficacy; docetaxel; toxicity