title: Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D-α-tocopheryl polyethylene glycol 1000 succinate nanoemulsions.
abstract: BACKGROUND
  Acetylpuerarin (AP), because of its lower water solubility, shows poor absorption that hinders its therapeutic application. Thus, the aim of this study was to prepare nanoemulsions for AP, enhance its oral bioavailability, and thus improve the therapeutic effect.
  
  
  METHODS
  The nanoemulsions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by high-pressure homogenization and characterized in terms of particle size, drug loading, morphology, and in vitro drug release. A lipid digestion model was used to predict in vivo drug solubilization in the gastrointestinal environment. The pharmacokinetics of AP formulations were performed in rats; meanwhile, a chylomicron flow-blocking rat model was used to evaluate the lymphatic drug transport. Moreover, the therapeutic effects of AP nanoemulsions on the model of focal cerebral ischemia-reperfusion for brain injury were also assessed.
  
  
  RESULTS
  The nanoemulsions with a droplet size of 150 nm were well stabilized by TPGS and showed a high loading capacity for AP. In the digestion model, the distribution of AP in aqueous phase/pellet phase was about 90%/10% for nanoemulsions and 5%/95% for oil solution, indicating that the drug encapsulated in nanoemulsions would present in solubilized form after transportation into the gastrointestinal tract, whereas drug precipitation would occur as the oil solution was orally administered. The area under the curve value of AP nanoemulsions was 5.76±0.56 μg·hour·mL(-1), or was about 2.6 and 1.7 times as great as that of suspension and oil solution, respectively, indicating enhanced drug absorption and thus achieving a better neuroprotection effect on cerebral ischemic reperfusion injury. The values of peak plasma concentration and area under the curve from the blocking model were significantly less than those of the control model, suggesting that the lymphatic transport performed a very important role in absorption enhancement.
  
  
  CONCLUSIONS
  Enhanced oral bioavailability in nanoemulsions was achieved via the mechanism of the maintenance of drug solubilization in the gastrointestinal tract and the enhancement of lymphatic transport, which resulted in therapeutic improvement of cerebral ischemic reperfusion injury.
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan, People's Republic of China ; Department of Pharmacy, Second Hospital of Shandong University, Jinan, People's Republic of China.
authors: Deqing
authors: D
authors: Sun
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan, People's Republic of China.
authors: Xinbing
authors: X
authors: Wei
authors: Department of Pharmacy, Second Hospital of Shandong University, Jinan, People's Republic of China.
authors: Xia
authors: X
authors: Xue
authors: Department of Clinical Pharmacology, Second Hospital of Shandong University, Jinan, People's Republic of China.
authors: Zengjun
authors: Z
authors: Fang
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan, People's Republic of China.
authors: Manru
authors: M
authors: Ren
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan, People's Republic of China.
authors: Haiyan
authors: H
authors: Lou
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan, People's Republic of China.
authors: Xiumei
authors: X
authors: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007529:Isoflavones / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D065568:Oral Mucosal Absorption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D004655:Emulsions; D007529:Isoflavones; C521069:acetylpuerarin; D014810:Vitamin E; C014225:tocophersolan
keywords: TPGS; absorption; chylomicron flow-blocking rat model; lipid digestion; lymphatic transport; nanoemulsions; transient middle cerebral artery occlusion rat model