title: A novel cabazitaxel-loaded polymeric micelle system with superior in vitro stability and long blood circulation time.
abstract: Cabazitaxel (CTX) is a second-generation semisynthetic taxane that demonstrates antitumor activity superior to docetaxel. However, the low aqueous solubility of CTX has hampered its use as a therapeutic agent. In this work, CTX-loaded N-t-butoxycarbonyl-L-phenylalanine end-capped monomethyl poly (ethylene glycol)-block-poly (D,L-lactide) (mPEG-PLA-Phe(Boc)/CTX) micelles were prepared to improve the solubility of CTX while retaining its superior stability before accessing the tumor site. The mPEG-PLA-Phe(Boc)/CTX micelles showed excellent stability in vitro compared with mPEG-PLA/CTX micelles. When stored at 25 °C, the mPEG-PLA/CTX micelles tended to aggregate within 1 h, whereas the mPEG-PLA-Phe(Boc)/CTX micelles were uniformly transparent even after three weeks. Dilution of mPEG-PLA/CTX micelles widened their size distribution and decreased the encapsulation efficiency, while significant change was not found in mPEG-PLA-Phe(Boc)/CTX micelles, even when diluted 1000-fold. Pharmacokinetic results in Sprague-Dawley rats indicated that, compared with Jevtana(®), intravenous administration of mPEG-PLA-Phe(Boc)/CTX micelles stably retained the CTX in plasma with 26.03-fold larger of the area under the time-concentration curve, 2.13-fold longer of the half-life, and 9.99-fold higher of the maximum concentration. In conclusion, mPEG-PLA-Phe(Boc) micelle may be a potential nanocarrier not only to improve the solubility of CTX but also to prolong the blood circulation time, which results in improved biological activity.
authors.affiliation: a State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology , East China University of Science and Technology , Shanghai , China.|b School of Biotechnology , East China University of Science and Technology , Shanghai , China.
authors.forename: Xiaoxiong
authors.initials: X
authors.lastname: Han
authors.affiliation: a State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology , East China University of Science and Technology , Shanghai , China.|b School of Biotechnology , East China University of Science and Technology , Shanghai , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology , East China University of Science and Technology , Shanghai , China.|b School of Biotechnology , East China University of Science and Technology , Shanghai , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: d Shanghai Yizhong Biotechnical Co., Ltd. , Shanghai , China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: d Shanghai Yizhong Biotechnical Co., Ltd. , Shanghai , China.
authors.forename: Duan
authors.initials: D
authors.lastname: Li
authors.affiliation: c Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering , East China University of Science and Technology , Shanghai , China.
authors.forename: Feirong
authors.initials: F
authors.lastname: Gong
authors.affiliation: a State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing Technology , East China University of Science and Technology , Shanghai , China.|b School of Biotechnology , East China University of Science and Technology , Shanghai , China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000818:Animals; D001776:Blood Circulation Time; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D008297:Male; D008823:Micelles; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D043823:Taxoids; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; C552428:cabazitaxel
keywords: Cabazitaxel; blood circulation time; polymeric micelle; stability