Improvement of oral availability of ginseng fruit saponins by a proliposome delivery system containing sodium deoxycholate

Abstract

Ginseng fruit saponins (GFS) extracted from the ginseng fruit are the bioactive triterpenoid saponin components. The aim of the present study was to develop a drug delivery system called proliposome using sodium deoxycholate (NaDC) as a bile salt to improve the oral bioavailability of GFS in rats. The liposomes of GFS were prepared by a conventional ethanol injection and formed the solid proliposomes (P-GFS) using spray drying method on mannitol carriers. The formulation of P-GFS was optimized using the response surface methodology. The physicochemical properties of liposome suspensions including encapsulation efficiency, in vitro drug release studies, particle size of the reconstituted liposome were tested. The solid state characterization studies using the method of Field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) and Differential scanning colorimetric (DSC) were tested to study the molecular state of P-GFS and to indicate the interactions among the formulation ingredients. In vitro studies showed a delayed release of ginsenoside Re (GRe). In vivo studies were carried out in rats. The concentrations of GRe in plasma of rats and its pharmacokinetic behaviors after oral administration of GFS, Zhenyuan tablets (commercial dosage form of GFS) and P-GFS were studied using ultra performance liquid chromatography tandem mass spectrometry. It was founded that the GRe concentration time curves of GFS, Zhenyuan tablets and P-GFS were much more different in rats. Pharmacokinetic behaviors of P-GFS showed a second absorption peak on the concentration time curve. The pharmacokinetic parameters of GFS, Zhenyuan tablets, P-GFS in rats were separately listed as follows: T max 0.25 h, C max 474.96 ± 66.06 ng/ml and AUC0-∞ 733.32 ± 113.82 ng/ml h for GFS; T max 0.31 ± 0.043 h, C max 533.94 ± 106.54 ng/ml and AUC0-∞ 1151.38 ± 198.29 ng/ml h for Zhenyuan tablets; T max 0.5 h, C max 680.62 ± 138.051 ng/ml and AUC0-∞ 2082.49 ± 408.33 ng/ml h for the P-GFS. The bioavailability of P-GFS was nearly 284% and 181% of the GFS and Zhengyuan tablets respectively. In conclusion, the proliposomes significantly enhanced the drug bioavailability, absorption in the gastrointestinal tract and decreased its elimination time of GRe in rats and could be selectively applied for oral delivery of GFS.

Ginseng Nanoparticles Protect Against Methotrexate-Induced Testicular Toxicity in Rats

“…As well known, the potency of the ginseng extract is often measured by the percentage of contained ginsenosides. Total ginsenosides content of the ginseng extract may vary by species of ginseng, cultivation conditions, [22] method of processing and the part of the plant from which the extract is prepared [41].…”

“…The rationale of using nanoformulation of ginseng extract in the current study was to improve its pharmacokinetic properties since ginseng oral bioavailability is known to be very poor [22,41]. Oral bioavailability of ginseng can be enhanced by increasing the dose to saturate its metabolism or by changing its pharmaceutical formulation [22] such as nanoparticles formulation [23,43].…”

Low Cerebral Exposure Cannot Hinder the Neuroprotective Effects of Panax Notoginsenosides

“…We found that pretreatment with PNE (100 mg/kg) for 7 consecutive days before cerebral I/R could significantly decrease levels of proinflammatory cytokines, reduce the volume of brain infarcts, attenuate neurologic deficits, and maintain BDNF levels in the hippocampus even though exposure to each component of PNE was extremely low in the brains of normal and I/R rats. For herbal saponins, oral bioavailability is often limited owing to low membrane permeability, high molecular weight, fast clearance in the GI tract, and efflux transporters (Hao et al, 2016). Clinically, some commercial PNE formulations cure cerebral diseases mainly after intravenous administration, as exemplified by the Xue-Sai-Tong injection.…”

Study of Absorption Characteristics of the Total Saponins from Radix Ilicis Pubescentis in an In Situ Single-Pass Intestinal Perfusion (SPIP) Rat Model by Using Ultra Performance Liquid Chromatography (UPLC)

“…However, the apparent oil-water partition coefficient test ( Figure 7 ) showed that all of the six saponins had suitable liposolubility as far as druggability was concerned, with a K ow value between −2 and 1, and C1, C2, and C3 monomers also exhibiting good membrane permeability. Previously, the absolute oral bioavailability of C1 could be only calculated based on literature data [ 12 , 34 ], which yielded a low value. The permeability of the six saponin monomers decreased with an increase in the number of glycoside groups ( Figure 6 ), and pentacyclic triterpenoid saponins were investigated as a class of ingredients with poor oral bioavailability [ 34 , 35 ].…”