title: Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: preparation and comparison with other paclitaxel systems in vitro and in vivo.
abstract: Previously, PEGylated paclitaxel (PEG-PTX) was found not favorable as a polymer prodrug because of its poor antitumor efficiency. But surprisingly, it was found in our study that PEG-PTX could form a novel nanoparticle system with free PTX. To address how this system works, we compared PTX loaded PEG-PTX nanoparticles (PEG-PTX/PTX) with PTX loaded PEG-PLA micelles (PEG-PLA/PTX) or PTX injection available (Taxol(®)) in vitro and in vivo. Firstly, it was found that PEG-PTX/PTX was more stable in aqueous solution than PEG-PLA/PTX in terms of PTX crystal formation and drug release. Then it was demonstrated that coumarin loaded PEG-PTX nanoparticles had a much higher uptake in MCF-7 cells compared to coumarin loaded PEG-PLA micelles. The in vivo imaging study revealed that DIR or DID (near infrared fluorescent substances) loaded PEG-PTX nanoparticles distributed more in tumors in MCF-7 tumor bearing mice than DIR or DID loaded PEG-PLA micelles and solvent system of Taxol(®). In the efficacy study with MCF-7 tumor bearing mice, PEG-PTX/PTX showed significantly higher antitumor activity than PEG-PLA/PTX at the same PTX dosage. At the dose of 10mg free PTX per kg, PEG-PTX/PTX displayed similar efficacy as Taxol(®) but less toxicity evaluated by the loss of body weight. With the increase of free PTX to 15 mg/kg, PEG-PTX/PTX showed significantly better efficacy than Taxol(®). In conclusion, with favorable characteristics in stability, cellular uptake, cytotoxicity, biodistribution, safety and efficacy, PEG-PTX/PTX seems highly potential as a nanocarrier for PTX delivery.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Chuan
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
authors.forename: Xinglin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: wangxq@bjmu.edu.cn.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: zqdodo@bjmu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: Antitumor effect; Nanoparticles; PEG-PLA; PEGylated paclitaxel; Paclitaxel; Taxol