ABSTRACT
Objective: To prepare a drug delivery system based on L-carnitine modified and quercetin (QUE)-coloading chitosan-stearic acid (LC-SA/CS-SA) nanomicelles, investigate the properties of micelles, and evaluate the enhanced absorption effect of the micelles by in vivo intestinal absorption in rats. Methods: The CS-SA copolymer was synthesized by the amidation of free amino groups on CS. The chemical structure of CS-SA was characterized by Fourier transform-infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Taking PTX was the main drug and quercetin as the auxiliary drug, the particle size distribution, Zeta potential, drug loading and entrapment efficiency of the micelles were investigated. The micromorphology of the micelles was observed by transmission electron microscope (TEM). The critical micelle concentration (CMC) of LC-SA/CS-SA micelles was measured by fluorescent probe method. The in vitro release of paclitaxel from polymeric micelles was evaluated by dialysis method. The absorption rate coefficient (Ka) of paclitaxel (PTX)-loaded micelles was assessed by in vivo intestine absorption in rats. Results: The results of FT-IR and 1HNMR indicated that the copolymer (CS-SA) was synthesized. The LC-SA/CS-SA@ QUE+PTX micelles showed regular spherical shapes with particle size of (148.3 ± 1.7) nm, PDI of 0.16 ± 0.07, Zeta potential of (24.600 ± 0.167) mV and CMC of 14.31 µg/mL. Compared to the commercial formulation of PTX, LC-SA/CS-SA@QUE+PTX micelles and LC-SA/CS-SA@PTX micelles showed significantly sustained release behaviors. The enhanced absorption effect of PTX in the micelle system was confirmed by intestine absorption test in rats. Conclusion: The LC-SA/CS-SA@QUE+PTX micelles, as a potential oral absorption promoter, enhanced the intestinal absorption of PTX in rats.
ABSTRACT
To study the in vivo intestinal absorption kinetics of phloridzin in rats. The absorption of phloridzin in the small intestines and colon of rats was investigated using an in vivo single-pass perfusion method and the drug concentration was measured by HPLC. The effects on intestinal absorption of different drug concentration and P-glycoprotein (P-gp) inhibitor were conducted. The results showed that the phloridzin could be absorbed in whole intestine, but more fully in the jejunum and colon segment,poorly absorbed in the duodenum and ileum. The absorption rate constant (Ka) and the apparent absorption coefficient（Papp）of phloridzin decreased following the sequence of jejunum> colon > duodenum > ileum. Absorption parameters of phloridzin had no significant difference at different concentration (5.14, 10.28, 20.56 mg•L⁻¹) . The saturate phenomena was not observed under the test range of drug concentration, and the absorption mechanism may be the passive diffusion transport.There had a significant difference in Ka and Papp values between P-gp inhibitor and no P-gp inhibitor groups. Phloridzin may be the substrate of P-gp.
ABSTRACT
Objective: To investigate the intestinal absorption characteristics of α-hederin and to explore the causes of poor bioavailability. Methods: In vivo single-pass perfusion model was used and the concentration of α-hederin was determined by HPLC. The effects of intestinal segment, drug concentration, pH value, gut microflora, and P-gp inhibitor on the intestinal absorption of the drug were investigated. Results: The absorption rate constant (Ka) of α-hederin decreased following the sequence of ileum > colon > jejunum > duodenum. Absorption parameters of α-hederin had no significant difference at different concentration of 75, 150, and 300 μg/mL and those increased with the increase of pH value. The intestinal flora which were disrupted may affect the absorption of α-hederin. There was no significant difference in Ka and Peff values between P-gp inhibitor and no P-gp inhibitor groups. Conclusion: α-Hederin can be absorbed in whole intestine, but better in lower intestine. The saturate phenomena was not observed under the test range of drug concentration, and the absorption mechanism may be the passive diffusion transport. The absorption can be better under basic condition. The absorption is significantly affected by the intestinal flora and α-hederin is not the substrate of P-gp.