title: Andrographolide-loaded PLGA-PEG-PLGA micelles to improve its bioavailability and anticancer efficacy.
abstract: BACKGROUND
  Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application.
  
  
  OBJECTIVE
  In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo.
  
  
  METHODS
  The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat.
  
  
  RESULTS
  ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 - ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension.
  
  
  CONCLUSIONS
  All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy.
authors.affiliation: University of Macau, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine , Av. Padre Tomas Pereira S.J., Taipa, Macau 999078 , China +853 83974696; +853 83974691 ; +853 28841358 ; mwchen@umac.mo ; ytwang@umac.mo.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D008823:Micelles; D011108:Polymers; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; C030419:andrographolide
keywords: andrographolide; breast cancer MAD-MB-231 cells; micelles; pharmacokinetics; poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) triblock copolymer