In the present study, liquiritigenin-phospholipid complex (LPC) was developed and evaluated to increase the oral bioavailability of liquiritigenin. A single-factor test methodology was applied to optimize the formulation and process for preparing LPC. The effects of solvent, drug concentration, reaction time, temperature and drug-to-phospholipid ratio on encapsulation efficiency were investigated. LPCs were characterized by UV-visible spectroscopy, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (PXRD). The apparent solubility and n-octanol/water partition coefficient were tested. The pharmacokinetic characteristics and bioavailability of the LPC were investigated after oral administration in rats in comparison with liquiritigenin alone. An LPC was successfully prepared. The optimum level of various parameters for liquiritigenin-phospholipid complex was obtained at the drug concentration of 8 mg·mL
Administration, Oral ; Animals ; Biological Availability ; Flavanones/pharmacokinetics* ; Phospholipids/pharmacokinetics* ; Rats ; Solvents

To investigate the absorption kinetics of Cu B-SDC/PLC-MMs in rat different intestinal segments and compared with the absorption of Cu B suspension. The in vitro everted gut sacs model was established to study the absorption characteristics of Cu B-SDC/ PLC-MMs in rat duodenum, jejunum, ileum and colon, and the content of cucurbitacin B was detected by HPLC method, and the effects of concentrations on intestinal absorption were evaluated as well. The results showed that the absorption of Cu B-SDC/PLC-MMs was linearity at different intestine segment and different concentrations (R2 > 0.9), which was consistent with zero order rate process. The Ka of different intestine segments showed a concentration-dependent increasing along with the raised concentration of Cu B-SDC/ PLC-MMs, indicating that it was likely to be a mechanism of passive absorption. The best absorption site of Cu B-SDC/PLC-MMs was ileum, and its absorptions in different intestinal segments were superior to cucurbitacin B suspension. SDC/PLC-MMs could significantly enhance the intestinal absorption of cucurbitacin B, and the study of intestinal absorption kinetics of Cu B-SDC/PLC-MMs had gave a support to its further reasonable solidfication.
Animals ; Deoxycholic Acid ; administration & dosage ; Female ; Intestinal Absorption ; Kinetics ; Male ; Micelles ; Nanoparticles ; Phospholipids ; administration & dosage ; Rats ; Rats, Wistar ; Triterpenes ; administration & dosage ; pharmacokinetics

AIMTo prepare silybin-phospholipid complex and study its physicochemical properties. To compare the pharmacokinetic characteristics and bioavailability after oral administration of silybinphospholipid complex and silybin material in rats.

METHODSUsing acetone as a reaction medium, silybin and phospholipid were resolved into the medium, when the organic solvent was clear, then removed under vacuum evaporation, silybin-phospholipid complex was obtained. The new complex' s physicochemical properties including DSC, UV, IR were determined. The concentrations of non-conjugated and total silybin after oral administration of silybin-phospholipid complex and silybin material at different time in rats were determined by RP-HPLC. The pharmacokinetic parameters were computed by software program 3P97.

RESULTSExperiment results showed that silybin and phospholipid in the silybin-phospholipid complex were combined by non-covalent-bond, not forming a new compound and the solubility of silybin-phospholipid complex in water and n-octanol was effectively enhanced. It was found that mean plasma concentration-time curve of silybin after oral administration of silybin-phospholipid complex in rats was in accordance with one-compartment model with first-order absorption. Pharmacokinetic parameters of non-conjugated and total silybin in rats were respectively T(max) 10 min and 2 h; C(max) 0.11 and 1.08 microg x mL(-1); T1/2 2.18 and 3.84 h; AUC(0-infinity) 1.71 and 12.94 microg x mL(-1) x h. However, after oral administration of silybin material, plasma levels of both non-conjugated and total silybin were within the analytical detection limit.

CONCLUSIONIt was concluded that after oral administration of silybin-phospholipid complex in rats the bioavailability of silybin increased greatly. This was mainly due to an obvious improvement of the lipophilic property of silybin-phospholipid complex compared with silybin material and an increase in gastrointestinal absorption.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Drug Compounding ; Male ; Phospholipids ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Silymarin ; administration & dosage ; blood ; pharmacokinetics ; Solubility

OBJECTIVETo evaluate the effect of a phospholipid-coated microbubble contrast agent for myocardium opacification in comparison with a albumin-coated microbubble contrast agent (Quanfuxian).

METHODSIn 10 dogs with single coronary artery stenosis involving the anterior descending branch or circumflex branch randomly received infusion of the two contrast agents through the femoral vein. The myocardial blood flow, heart rate and blood pressure were analyzed qualitatively and quantitatively. The concentration and the particle diameter of the two contrast agents were determined.

RESULTSThe concentration of the phospholipid-coated microbubbles was (1.06-/+0.22) x10(9)/ml, with a diameter of 3.04-/+0.34 microm, similar to the concentration and diameter of Quanfuxian ((1.31-/+0.33)x10(9)/ml and 2.88-/+0.58 microm, respectively, P>0.05). Both of the agents achieved grade three myocardium opacification, and produced no obvious effect on the heart rate and blood pressure. Quantitative analysis of myocardial opacification in terms of myocardial blood volume (A), blood velocity (beta), and blood flow (A x beta) revealed no significant difference between the two agents (P>0.05), and the parameters derived from the two agents showed good correlations (P<0.05, rA=0.809, r beta=0.932, rA.beta=0.925).

CONCLUSIONThe phospholipid-coated microbubble contrast agent shows good effect for myocardial opacification without significant difference from Quanfuxian. Both of the agents are good ultrasound contrast agents for quantitative analysis of myocardium blood flow.

Albumins ; chemistry ; Animals ; Contrast Media ; administration & dosage ; chemistry ; Coronary Stenosis ; diagnostic imaging ; Dogs ; Echocardiography ; methods ; Female ; Male ; Microbubbles ; Phospholipids ; chemistry

OBJECTIVETo study the preparation of liposomes surface-modified with glycyrrhetinic acid targeting to hepatocytes.

METHOD3-succinic-30-stearyl glycyrrhetinic acid(Suc-GAOSt), one of the amphiphilic glycyrrhetinic acid derivatives, was synthesized as targeting molecules, liposomes surface-modified with glycyrrhetinic acid has been produced with ethanol injection method.

RESULTTargeting molecules can be mixed into the liposomal membrane. It was confirmed that the targeting molecules is 9% of the total lipids at the most in the liposomes.

CONCLUSIONLiposomes surface-modified with glycyrrhetinic acid was successfully prepared, which is considered to be a potential approach targeting to hepatocytes.

Drug Carriers ; Drug Delivery Systems ; methods ; Glycyrrhetinic Acid ; administration & dosage ; Hepatocytes ; Liposomes ; Particle Size ; Phospholipids ; Succinic Anhydrides

OBJECTIVETo prepare silybin lipid nanospheres (SLN) and to evaluate the properties of morphology, particle size and the silybin distribution in mice.

METHODSilybin lipid nanospheres were prepared by thin film emulsion-high pressure homogenization technique. Concentrations of silybin in mice blood, liver, spleen, lung, kidney, brain, heart, stomach after oral administration were determined by high performance liquid chromatography.

RESULTScanning electron micrograph showed that most of the SLN were spherical. The average diameter from photon correlation spectrometer was 148.9 nm with the polydispersity 0.17. Body distribution data indicated that SLN could increase the distribution of silybin in blood and liver, decrease the amount of silybin in stomach as compared with the preparation on market, and the drug targeting index (DTI) in liver was 1.81.

CONCLUSIONSLN can increase the uptake of silybin in liver after oral administration, which must benefit the hepatitis treatment.

Administration, Oral ; Animals ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Liver ; metabolism ; Mice ; Nanoparticles ; Particle Size ; Phospholipids ; Random Allocation ; Silymarin ; administration & dosage ; pharmacokinetics ; Tissue Distribution

Apolipoprotein, an important component of the lipoproteins, modulates the activity of enzyme, introduces the binding of cell receptor and lipoproteins, and keeps the structural stability of lipoproteins. The amphipathic helices structure in apolipoproteins is the structural basis that it binds and transports lipids. A certain envelope glycoprotein (gp) in the outer membrane of HIV also has been found to be with such amphipathic helices structure. Recent studies have shown that the liposome consisted of apolipoproteins and phospholipids may defend against HCV, HIV, and herpes simplex virus, and even neutralize the endotoxin released by bacteria. The liposome made up of apolipoproteins and phospholipid has became a potential carrier for anti-tumor and anti-virus drugs.
Animals ; Antineoplastic Agents ; administration & dosage ; Antiviral Agents ; administration & dosage ; Apolipoproteins ; chemistry ; physiology ; Genetic Therapy ; methods ; Humans ; Liposomes ; chemistry ; Phospholipids ; chemistry ; Protein Conformation ; Virus Diseases ; drug therapy ; prevention & control

A novel drug delivery system combining oral fast dissolving film with sodium deoxycholate/phospholipid mixed micelles was prepared to increase the absorption of cucurbitacin B that is a poor aqueous solubility substance. Encapsulation efficiency, particle size, zeta potential, polydispersity coefficient, investigated the morphology, disintegration time of oral fast dissolving film and the pharmacodynamic properties of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles before and after solidified in mice were evaluated and compared. The oral fast dissolving film prepared in this study showed a homogeneous pale yellow and could completely disintegrated in the 30 s. It could meet the requirements of rapidly disintegrating fully. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles loaded in oral fast dissolving film were (43.36 +/- 2.12)%, (108.82 +/- 5.2) nm, (-34.18 +/- 1.07) mV, 0.088 +/- 0.012, respectively. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles in solution were (41.26 +/- 2.22)%, (181.82 +/- 4.48) nm, (-30.67 +/- 0.81) mV, 0.092 +/- 0.012, respectively. The difference of pharmacodynamics among film of cucurbitacin B-loaded micelles, cucurbitacin B-loaded micelles and free cucurbitacin B in vivo was compared. Solubility of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles has also been greatly improved. The tumor inhibition rate of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles was significantly improved and did not change significantly before and after solidified. These showed that the sodium deoxycholate/phospholipid-mixed micelles could enhance the antitumor activities of cucurbitacin B and the stability of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles was improved significantly after solidified by oral fast dissolving film technology without pharmacodynamic properties changed significantly.
Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; Cell Line, Tumor ; Deoxycholic Acid ; chemistry ; Drug Carriers ; chemistry ; Humans ; Male ; Mice ; Neoplasms ; drug therapy ; Phospholipids ; chemistry ; Solubility ; Triterpenes ; administration & dosage ; chemistry

OBJECTIVETo study the plasma concentration-time curve, pharmacokinetic parameters and bioavilability of oxymatrine-phospholipid complex and to compare with oxymatrine in rats.

METHODRats were given oxymatrine-phospholipid 100 mg x kg(-1). Blood samples were collected at different times after oral administration. The internal standard was cimetidine. Protein in plasma was precipitated with merhanol and centrifuged at high speed. The supernatant was directly injected and assayed by CE method. The running buffer was 0.04 mol x L(-1) Tris-10 mmol x L(-1) sodium phosphate monobasic-40% isopropanol pH to 7.6 with phosphoric acid. The wavelength of detection was 205 nm.

RESULTThe AUC of oxymatrine and oxymatrine-phospholipid complex were 4.52 mg x mL(-1) x h(-1) and 6.21 mg x mL(-1) x h(-1), respectively. The oxymatrine-phospholipid bioavailability enhanced 1.4 times.

CONCLUSIONIt is concluded that after oral administration of oxymatrine-phospholipid complex in rats the bioavailability of oxymatrine is increased greatly. This is mainly due to an obvious improvement of the lipophilic property of oxymatrine-phospholipid complex compared with oxymatrine material and an increase in gastrointestinal absorption.

Administration, Oral ; Alkaloids ; administration & dosage ; chemistry ; pharmacokinetics ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; chemistry ; pharmacokinetics ; Area Under Curve ; Biological Availability ; Male ; Phospholipids ; chemistry ; Plants, Medicinal ; chemistry ; Quinolizines ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Sophora ; chemistry

OBJECTIVETo investigate whether the absorption of breviscapine can be enhanced by using breviscapine photosomes.

METHODTesting the uptake and intestinal permeability of breviscapine powder and breviscapine photosomes by using intestine perfusion technique and reverted gut sac method.

RESULTThe uptake and permeability coefficient of breviscapine were increased in photosomes. The absorption process obeyed the Fick's law in the range of 0-100 microg x mL(-1).

CONCLUSIONThe absorption breviscapine photosomes is enhanced by increasing the permeability through a passive mechanism.

Animals ; Asteraceae ; chemistry ; Drug Carriers ; Flavonoids ; administration & dosage ; isolation & purification ; pharmacokinetics ; Intestinal Absorption ; Intestine, Small ; metabolism ; Male ; Phospholipids ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley