A novel cabazitaxel-loaded polymeric micelle system with superior in vitro stability and long blood circulation time. Issue 7 (2nd May 2016)

• Record Type: Journal Article
• Authors: Han, Xiaoxiong; Chen, Dan; Sun, Jing; Zhou, Jinsong; Li, Duan; Gong, Feirong; Shen, Yaling
• Is Part Of: Journal of biomaterials science. Volume 27:Issue 7(2016)
• Page Start: 626
• Page End: 642
• Publication Date: 2016-05-02
• Subjects: Cabazitaxel -- polymeric micelle -- stability -- blood circulation time; Polymers -- Biocompatibility -- Periodicals; Biomedical materials -- Periodicals; 572.33
• DOI: 10.1080/09205063.2016.1146980
• Languages: English
• ISSNs: 0920-5063

Abstract

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.