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OBJECTIVE: To investigate the absorption mechanism of paeoniflorin in Radix Paeoniae Alba, both of Radix Paeoniae Alba and Radix Angelica Sinensis and Siwu Decoction. METHODS: The circulatory perfusion technique was used in this study, the concentrations of paeoniflorin and phenol red in intestinal absorption circulation were respectively determined by HPLC and UV. The effects of pH value, drug concentration, absorption site and P-gp on the absorption of paeoniflorin were investigated separately. RESULTS: By comparing the absorption of paeoniflorin in Radix Paeoniae Alba, both of Radix Paeoniae Alba and Radix Angelica Sinensis, and Siwu Decoction, it was found that in the sample solution at the same absorption site, pH value and concentration (based on the concentration of paeoniflorin), the absorption, Ka and cumulative absorption of paeoniflorin in compound Siwu decoction group were significantly increased compared with the other groups (P<0.05), while t1/2 was significantly decreased (P<0.05). When combined with the inhibitor and inducer of P-gp, the absorption of paeoniflorin showed significant increase or decrease in the amount of absorption, Ka and cumulative absorption% compared with the control group (P<0.05), and t1/2 also showed significant decrease or increase (P<0.05). CONCLUSION: The absorption of paeoniflorin could be affected by P-gp, and under the same conditions, the absorption of paeoniflorin in complicated Chinese herbal formula is better than that in the single herb and herb-pair.
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Objective: To investigate the effects of particles in coptis (Coptidis Rhizoma)-decoction on the berberine absorption in intestine. Methods: The particles in copitis-decotion were separated by the high-speed centrifugation and weak-base anion-exchange resin. The characteristics of berberine absorption in intestine were evaluated by the in situ intestinal perfusion in rats. Results: Although each segment of small intestine exhibited obvious berberine absorption, the jejunum exhibited the highest absorption rate constant (Ka) of (3.587 9 ± 0.005 2) × 10-4/s and effective permeability coefficient (Peff) of (4.529 4 ± 0.009 7) × 10-5 cm/s. Particles P1 and P2, with similar size of (272.7 ± 25.2) and (264.8 ± 21.4) nm and different surface potential of (-6.85 ± 0.16) and (-18.20 ± 0.71) mV, were obtained from the copitis-decotion. Particle P1 could significantly improve the berberine absorption in intestine, with Ka of (5.853 6 ± 0.970 1) × 10-4/s and Peff of (8.082 4 ± 1.004 2) × 10-5 cm/s. Conclusion: Particles in coptis-decotion can improve the berberine absorption in intestine. The surface potential of the particles may be responsible for the improvement of berberine absorption.
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Objective To study the intestinal absorption characteristics of evodiamine (EVO) hydroxypropyl-β-cyclodextrin inclusion complex (EHD) in rats. Methods EHD was prepared and its physicochemical properties were determined. Healthy male SD rats were randomly divided into two groups. One-way intestinal perfusion rat model was employed to investigate the intestinal absorption of EVO in each segment. The concentrations of the EVO were determined by HPLC (Lichrospher C18 column[250 mm×4. 6 mm, 5 μm]), with the mobile phase being methanol-water (75:25), flow rate being 1. 0 mL/min, the detection wavelength being set at 225 nm, and the column temperature being 35℃. The absorption rate constants (Ka) and effective permeability coefficients (Peff) were calculated. Results The characteristic endothermal peak of EVO was decreased in the fourier transform infrared spectroscopy of EHD, and differential scanning calorimetry (DSC) of EHD showed that the endothermic peak of EVO was greatly reduced. The morphological character of EHD under electron microscope was obviously different from that of the physical mixture of EVO and hydroxypropyl-β-cyclodextrin. The coefficient of recovery and precision of EVO in the intestinal perfusion liquid met the requirement. The Ka values of EHD in the duodenum, jejunum, ileum, and colon were 9. 07, 16. 22, 11. 04, and 28. 86 folds that of the free EVO, respectively, showing significant differences between the two groups (P<0. 05). The Peff values of EHD in the duodenum, jejunum, ileum, and colon were 2. 41, 1. 52, 1. 82, and 1. 09 folds that of the free EVO, respectively, showing significant difference between the two groups only at the duodenum (P<0. 05), not at the jejunum, ileum or colon. Conclusion EHD can significantly improve the intestinal absorption of the EVO in rats.
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Objective To study the in situ intestinal absorption behaviors of 3, 29- dibenzoyl- karounitriol (DK) in Gualou- Xiebai (GX) extract in rats. Methods A rat in situ single-pass perfusion model was used and the concentrations of the perfusate were determined by HPLC-PDAD to investigate the intestinal absorption site and mechanism. Results The main absorption site of DK in GX extract was jejunum, ileum and colon, and the absorption had no significant difference in the three different segments of rat intestine (P>0.05), but was significantly higher than that in duodenum (P0.05). Conclusion DK in GX extract could be absorbed in whole intestinal segment, with the best intestinal absorption site of jejunum, ileum and colon. Its absorbing mechanism may be related to passive diffusion.
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Aim To study the absorption kinetics of se-ries molecular weight 5-ASA-mPEG in rats intestine. Methods The in situ intestinal absorption property of 5-ASA-mPEG in rats was investigated by means of sin-gle-pass perfusion, and HPLC method was established to determine the drug concentration in the perfusate. Results The drug concentration and the site of intes-tine segments had little effect on the drug absorption constant ( Ka ) and apparent absorption coefficient (Papp). The perfusion flow rate and the variable mo-lecular weight of 5-ASA-mPEG could significantly af-fect the Ka and Papp. Conclusion 5-ASA-mPEG can be absorbed at all segments of the intestine of rats and has no specific absorption site. It is preliminarily in-ferred that the absorption mechanism of 5-ASA-mPEG is passive transportation. The intestinal absorption of 5-ASA-mPEG shows a downward trend with the increase in molecular weight. The results shows that the modifi-cation of 5-ASA by PEG can effectively inhibit the in-testinal absorption of mesalazine.
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Objective To study the in situ intestinal absorption behaviors of 3,29-dibenzoyl-karounitriol(DK)in Gualou-Xiebai(GX)extract in rats. Methods A rat in situ single-pass perfusion model was used and the concentrations of the perfusate were determined by HPLC-PDAD to investigate the intestinal absorption site and mechanism. Results The main absorption site of DK in GX extract was jejunum,ileum and colon,and the absorption had no significant difference in the three different segments of rat intes?tine(P>0.05),but was significantly higher than that in duodenum(P0.05). Conclusion DK in GX extract could be absorbed in whole intestinal segment,with the best intestinal absorption site of jejunum,ileum and colon. Its absorbing mechanism may be related to passive diffusion.
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AIM@#To improve the absorption of thymopeptides (TH) by preparing sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs).@*METHODS@#TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as their physical stability after storage for several days. Furthermore, in situ intestinal single-pass perfusion experiments and pharmacodynamics in immunodeficient mice were performed to make a comparison with TH powders and the control drug in absorption properties.@*RESULTS@#A narrow size distribution of nanomicelles, with a mean particle size of (149 ± 8.32) nm and a zeta potential of (-31.05 ± 2.52) mV, was obtained. The in situ intestine perfusion experiments demonstrated a significant advantage in absorption characteristics for TH compared to the other formulations, and oral administration of TH-SDC/PL-MMs potentiated an equivalent effect with i.h. TH in pharmacodynamic studies in immunodeficient mice.@*CONCLUSIONS@#TH-SDC/PL-MMs prepared by a film dispersion method are able to improve the absorption of TH. SDC/PL-MMs might be a good approach for the more effective delivery of drugs like TH.
Subject(s)
Animals , Mice , Rats , Chemistry, Pharmaceutical , Deoxycholic Acid , Chemistry , Drug Carriers , Chemistry , Drug Stability , Micelles , Particle Size , Peptides , Chemistry , Pharmacokinetics , Phospholipids , Chemistry , Rats, Wistar , Thymus Gland , ChemistryABSTRACT
OBJECTIVE: To improve the oral bioavailability of glycyrrhizin by preparing glyeyrrhizin-sodium deoxycholate/phos-pholipid-mixed micelles (GL-SDC/PL-MMs). METHODS: GL-SDC/PL-MMs was prepared by a film dispersion method. In order toevaluate the property GL-SDC/PL-MMs comprehensively, physical and chemical properties determination, in situ intestinal absorption, and pharmacokinetics test were carried out. RESULTS: The average particle size of drug-loaded micelles prepared by film dispersion method was (82.99±7.5) nm and Zeta potential was (-32.23±1.05) mV. Compared with the control drug, glycyrrhizin loaded in SDC/PL-MMs significantly improved its in situ intestinal absorption. The oral bioavailability was markedly enhanced, indicated by the increase of ρmax to 77.26 μg · mL-1, which was 2.82 times of that of the control drug. CONCLUSION: SDC/PL-MMs is expected to be developed into a new drug delivery systems of GL.
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Aim: To explore the in situ intestinal absorption in rats of ZLR-8, an insoluble NO-donor drug, and to compare the intestinal absorption enhancement by spray-dried emulsion. Methods: Intestine of rats was cannulat-ed for in situ perfusion. UV and HPLC methods were used to monitor phenolsulfonphthalein and ZLR-8, respec-tively. The effects on ZLR-8 absorption of the intestinal segments, the concentration of ZLR-8 and the pH of the circulating perfusate were studied. The absorption of ZLR-8 suspension was compared to that of the spray-dried emulsion. Results: 1-h in situ intestinal perfusion of the spray-dried emulsion allowed the estimation of the absor-tion percentage to be (23. 54 ± 1. 40) %, (15. 95 ± 0. 09) %, (12. 30 ± 0. 74) %, (3. 98 ± 0. 12) %, respec-tively; the absorption rate constants in duodenum, colon, jejunum and ileum to be (0.248 6 ±0.046 0) h~(-1), (0. 143 7 ±0. 036 0) h~(-1), (0. 069 2 ±0. 001 3) h~(-1), (0. 020 8 ±0. 000 4) h~(-1), respectively. Significant differ-ences in absorption characteristics were found among intestinal segments. In the range of 3. 4-9. 4, pH of the per-fuate had significant influence on the absorption of ZLR-8, and better absorption appeared at pH of 5. 4 to 7. 4. It was found that the absorption rate constant was unaffected by ZLR-8 concentration. However, the absorption amount was proportional to ZLR-8 concentration. Compared to the ZLR-8 suspension, the in situ intestinal absorption of ZLR-8 in rats given the spray-dried emulsion increased significantly. Conclusion: It was only found that ZLR-8 administered in suspension has minor absorption in rat duodenum while no apparent absorption occurred in other segemnts. ZLR-8 in spray-dried emulsion was fairly absorbed in the rat intestinal segments. Passive diffusion was invloved in the absorption of ZLR-8. Spray-dried emulsion significantly enhanced the intestinal absorption of ZLR-8 in rats.