Self-micelle formation and the incorporation of lipid in the formulation affect the intestinal absorption of Panax notoginseng.
The purpose of this research is to evaluate the effect of self-micelle formation and incorporation of lipid in the formulation on absorption of ginsenosides Rg1 and Rb1 from intestinal tract in rats. Ginsenosides Rg1 and Rb1 were extracted from Panax notoginseng saponins (PNS). The critical micellar concentration (CMC) of PNS in deionzied water was determined to be 0.339 mg/ml. At normal physiological ionic strengths, PNS was salted out from the solution above the CMC. The particle size of the micelle grows as PNS concentration increases. By in situ injection to a closed loop of the rat jejunum, AUC0-6h obtained after administration of low concentration solution (12 mg/ml) was 3.61 times for ginsenoside Rg1 and 3.84-folds for ginsenoside Rb1 compared with high concentration solution (120 mg/ml). The release rate of ginsenosides in aqueous medium was too slow to complete in 24h, especially for Rb1. The data suggested that the self-micelle formation tendency in ginsenosides might prevent them from permeation or absorption through the cell membrane of gastrointestinal (GI) tract. To inhibit the formation of micelles, lipid was incorporated in the PNS formulation. The intraduodenal bioavailability in rats showed that the bioavailability was enhanced remarkably relative to the aqueous solution. AUC 0-infinity of ginsenoside Rg1 and Rb1 in the lipid-based formulation were 207.52+/-53.95 and 1961.72+/-686.60 microg ml(-1) h, compared with 7.87+/-2.85 and 148.58+/-36.73 microg ml(-1) h, respectively from its aqueous solution. These findings suggested a new strategy to increase the absorption of amphiphilic saponins.
Xiong
Jing
J
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
Guo
Jianxin
J
Huang
Luosheng
L
Meng
Boyu
B
Ping
Qineng
Q
D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004386:Duodenum / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry; D036145:Ginsenosides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005989:Glycerides / Q000737:chemistry; D007408:Intestinal Absorption / Q000502:physiology*; D007441:Intubation, Gastrointestinal; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008823:Micelles; D053723:Panax notoginseng / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013500:Surface Tension
D005227:Fatty Acids; D036145:Ginsenosides; D005989:Glycerides; D008055:Lipids; D008823:Micelles; D010743:Phospholipids; D010936:Plant Extracts