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

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

  • J Colloid Interface Sci. 2017 Mar 15:490:542-552. doi: 10.1016/j.jcis.2016.11.089.
Xiufen Chen 1,  Jianzhong Chen 2,  Bowen Li 3,  Xiang Yang 1,  Rongjie Zeng 1,  Yajun Liu 1,  Tao Li 1,  Rodney J Y Ho 3,  Jingwei Shao 4
Affiliations

Affiliations

  • 1 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.
  • 2 School of Renewable Natural Resources, LSU Agricultural Center, Louisiana State University, Baton Rouge 70803, USA.
  • 3 Department of Bioengineering and Pharmaceutics, University of Washington, Seattle, WA 98195, USA.
  • 4 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: [email protected].
PMID: 27923139 DOI: 10.1016/j.jcis.2016.11.089
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.

Keywords

Anti-cancer; Oral drug delivery; PLGA–PEG–PLGA copolymers; Pharmacokinetic analysis; US597@micelles.

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