Polyamidomine dendrimers: an excellent drug carrier for improving the solubility and bioavailability of puerarin.
The potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers and oral drug delivery system was well known. Herein, we investigated the possibility of PAMAM dendrimers for promoting the solubility and oral bioavailability of puerarin. In the present study, the effect of PAMAM dendrimers with different generations (G1.5, G2, G2.5, and G3) on the solubility of puerarin was evaluated at different concentrations and pH conditions. Further more, the puerarin-G2 dendrimer complex was conducted for the in vitro hemolytic toxicity studies and pharmacokinetics studies in rats. The solubility of puerarin was significantly higher in the presence of the full generation dendrimers (e.g. G2 and G3). No significant hemolysis was observed on erythrocytes (G2, 0-2.5 mg/mL) in the hemolytic toxicity studies. The pharmacokinetics parameters Tmax, Cmax, and AUC0-8 h of puerarin suspension solution and puerarin-G2 dendrimer complex solution were 0.76 h, 1.50 µg/mL, 7.33 µg·h/mL and 0.33 h, 6.49 µg/mL, 14.02 µg·h/mL, respectively. These studies demonstrate that PAMAM dendrimers may be a promising strategy for peroral delivery of puerarin.
China Pharmaceutical University, State Key Laboratory of Natural Medicines, School of Pharmacy, Nanjing, China.
Lin
L
Gu
Zheng hong
Zh
Wu
Xiaole
X
Qi
Huan
H
He
Xiaoli
X
Ma
Xiaohua
X
Chou
Xiaoguang
X
Wen
Miao
M
Zhang
Fang
F
Jiao
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007529:Isoflavones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D050091:Dendrimers; D004337:Drug Carriers; D007529:Isoflavones; C104700:PAMAM Starburst; D019999:Pharmaceutical Solutions; D013535:Suspensions; C033607:puerarin