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. 30-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 (1JS597@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 my) 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 (C-max = 53 49 ng/mL, t1/2 = 8.716 +/- 7.033 h) over free US597 (C-max = 14 11 ng/mL, tl/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. (C) 2016 Elsevier Inc. All rights reserved.