Assessing the antifungal activity of a new oral lipid-based amphotericin B formulation following administration to rats infected with Aspergillus fumigatus

The purpose of this study was to assess the antifungal activity of a new oral amphotericin B (AmpB) lipid-based formulation following administration to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (2.1-2.5 × 10⁷ colony forming units [CFU]) were injected via the jugular vein; 48h later male albino Sprague-Dawley rats (350-400 g) were administered either a single oral dose of AmpB incorporated into Peceol (50 mg AmpB/kg), physiologic saline (nontreated controls) or Peceol alone (vehicle control) once daily for 4 days. To assess antifungal activity Brain, Lung, Heart, Liver, Spleen and Kidney sections were homogenized with normal saline (1 mL/g of tissue) and a 0.1-mL aliquot was spread plated onto a Sabourand dextrose agar plate. The plates were incubated for 48 hr at 37°C, at which time the number of fungal CFU were determined and corrected for tissue weight. In addition, plasma galactomannan antigen concentrations were determined. Data was reported as mean ± standard error of the mean. The AmpB-Peceol oral formulation significantly decreased total fungal CFU concentrations recovered in all the organs added together, brain CFU concentrations, spleen CFU concentrations and plasma galactomannan antigen concentrations compared to baseline. No significant differences in lung, heart, liver and kidney CFU concentrations between treatment and control groups were observed. Peceol vehicle control did not exhibit any antifungal activity. These findings suggest that a new oral lipid-based formulation of AmpB incorporated into Peceol can significantly decrease brain and spleen CFU concentrations and plasma galactomannan antigen concentrations compared to non-treated controls.     

The Use of Lipid-Based Formulations to Increase the Oral Bioavailability of Panax Notoginseng Saponins Following a Single Oral Gavage to Rats

Purpose: This article was intended to improve the absorption of ginsenoside Rg1 and Rb1 of Panax notoginseng saponins (PNS). Methods: PNS-Phospholipid complex and a lipid-based formulation by dissolving the complex in the medium chain fattyglycerides were prepared, and their oral relative bioavailability was determined in rats and compared with an aqueous solution of PNS for each component. Results: The study gave evidence that the phospholipids could combine with the two active constitutes of PNS and form a PNS-phospholipid complex. The complex efficiently increased the solubility of hydrophilic ginsenoside Rg1 and Rb1 in some selected hydrophobic esters, such as fatty glycerides, and constructed the lipid-based formulations of PNS. The experimental result in rats in vivo showed that the oral relative bioavailability was enhanced remarkably by these lipid-based formulations composed of the PNS-Phospholipid complex and various esters. The absorption enhancement of the medium-chain glyceride (Labrafac cc and Capmul MCM (3:1)) was somewhat greater than that of other fatty glyceride. The area under the plasma concentration-time curve (AUC) of ginsenoside Rg1 and Rb1 of the PNS-complex in the medium-chain glyceride were 27.38 μg.mL-1.h and 600.08 μg.mL-1.h, compared with 2.52 μg.mL-1.h and 92.29 μg.mL-1.h of the PNS aqueous solution, respectively. Conclusions: The oral relative bioavailability of ginsenoside Rg1 and Rb1 of PNS was enhanced remarkably by the lipid-based formulations. These findings reveal a new strategy to increase oral bioavailability by lipophilicity enhancement for some highly water-soluble but poorly absorbed drugs.