title: PLGA-PEG-PLGA triblock copolymeric micelles as oral drug delivery system: In vitro drug release and in vivo pharmacokinetics assessment.
abstract: 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 (<100nm), drug loading (25.9-28.5%), zeta potential (5.76-10.65mV) 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±49ng/mL, t1/2=8.716±7.033h) over free US597 (Cmax=14±11ng/mL, t1/2=16.433±8.821h). 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.
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Renewable Natural Resources, LSU Agricultural Center, Louisiana State University, Baton Rouge 70803, USA.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Bioengineering and Pharmaceutics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Rongjie
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Bioengineering and Pharmaceutics, University of Washington, Seattle, WA 98195, USA.
authors.forename: Rodney J Y
authors.initials: RJY
authors.lastname: Ho
authors.affiliation: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China. Electronic address: shaojingwei@fzu.edu.cn.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D056945:Hep G2 Cells; D006801:Humans; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C000603751:3-acetoxyurs-12-en-28-oic acid hexamethylenediamine; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D014315:Triterpenes; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols
keywords: Anti-cancer; Oral drug delivery; PLGA–PEG–PLGA copolymers; Pharmacokinetic analysis; US597@micelles