PLGA-PEG-PLGA triblock copolymeric micelles as oral drug delivery system: In vitro drug release and in vivo pharmacokinetics assessment

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• 作者：Xiufen Chen^a ; ¹ ; Jianzhong Chen^b ; ¹ ; Bowen Li^c ; Xiang Yang^a ; Rongjie Zeng^a ; Yajun Liu^a ; Tao Li^a ; Rodney J.Y. Ho^c ; Jingwei Shao^a ; ^{shaojingwei@fzu.edu.cn} ; ^{shaojw12@163.com}
• 关键词：UA ; Ursolic acid ; US597 ; a derivatives of UA ; US597@micelles ; the formulation of PLGA-PEG-PLGA tri-block micelles loaded with US597 ; PAMAM ; polyamidoamine ; SD rats ; Sprague&ndash ; Dawley rats ; UPLC/MS/MS ; Ultra-performance liquid chromatography tandem mass-spectrometry ; PEG ; polyethylene glycol ; PLGA ; poly(lactic-co-glycolic acid) ; MTBE ; methyl tertbutyl ether ; HepG2 ; Hepatocellular carcinoma cells ; B16F10 ; Melanoma cells ; SW620 ; Colon cancer cells ; DCC ; N ; N&prime ; -dicyclohexylcarbodiimide ; NHS
• 刊名：Journal of Colloid and Interface Science
• 出版年：2017
• 出版时间：15 March 2017
• 年：2017
• 卷：490
• 期：Complete
• 页码：542-552
• 全文大小：2741 K
• 卷排序：490

文摘

Poly (d,l-lactide-co-glycolide)-poly (ethylene glycol)-poly (d,l-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) has been proven to be desirable for anti-cancer drug delivery by intravenous administration. But till now there is no report of developing this micelle as a sustained oral formulation for cancer therapy. 3β-acetoxy-urs-12-en-28-oic acid hexamethylenediamine (US597), a derivative of natural product ursolic acid has been developed as a novel cancer metastasis chemopreventive agent by us. Herein, we developed a new oral dosage formulation of PLGA-PEG-PLGA tri-block micelles loaded with US597 (US597@micelles). US597@micelles was prepared by a double emulsion solvent evaporation method, and characterized in regards to mean diameter ( < 100 nm), drug loading (25.9–28.5%), zeta potential (5.76–10.65 mV) and encapsulation efficiency (55.7–74.3%), respectively. In vitro, US597@micelles could ameliorate sustained drug release, inhibit cell proliferation by inducing apoptosis (46.6% of late apoptosis), and influence the integrity of nuclei and mitochondrial on HepG2. Moreover, in vivo pharmacokinetic study by UPLC/MS/MS method demonstrated better absorption, metabolism and elimination characters of US597@micelles as an oral dosage form (Cmax = 53 ± 49 ng/mL, t1/2 = 8.716 ± 7.033 h) over free US597 (Cmax = 14 ± 11 ng/mL, t1/2 = 16.433 ± 8.821 h). In conclusion, PLGA-PEG-PLGA micelles as a promising oral drug delivery system are able to improve the bioavailability and efficacy of US597 in cancer therapy.