Catalpol improves impaired neurovascular unit in ischemic stroke rats via enhancing VEGF-PI3K/AKT and VEGF-MEK1/2/ERK1/2 signaling.

Neurovascular unit (NVU) is organized multi-cellular and multi-component networks that are essential for brain health and brain homeostasis maintaining. Neurovascular unit dysfunction is the central pathogenesis process of ischemic stroke. Thus integrated protection of NVU holds great therapeutic potential for ischemic stroke. Catalpol, classified into the iridoid monosaccharide glycoside, is the main active ingredient of the radix from traditional Chinese medicine, Rehmannia glutinosa Libosch, that exhibits protective effects in several brain-related diseases. In the present study, we investigated whether catalpol exerted protective effects for NVU in ischemic stroke and the underlying mechanisms. MCAO rats were administered catalpol (2.5, 5.0, 10.0 mg·kg-1·d-1, i.v.) for 14 days. We showed that catalpol treatment dose-dependently reduced the infarction volume and significantly attenuated neurological deficits score in MCAO rats. Furthermore, catalpol treatment significantly ameliorated impaired NVU in ischemic region by protecting vessel-neuron-astrocyte structures and morphology, and promoting angiogenesis and neurogenesis to replenish lost vessels and neurons. Moreover, catalpol treatment significantly increased the expression of vascular endothelial growth factor (VEGF) through up-regulating PI3K/AKT signaling, followed by increasing FAK and Paxillin and activating PI3K/AKT and MEK1/2/ERK1/2 pathways. The protective mechanisms of catalpol were confirmed in an in vitro three-dimensional NVU model subjected to oxygen-glucose deprivation. In conclusion, catalpol protects NVU in ischemic region via activation of PI3K/AKT signaling and increased VEGF production; VEGF further enhances PI3K/AKT and MEK1/2/ERK1/2 signaling, which may trigger a partly feed-forward loop to protect NVU from ischemic stroke.

[Analysis of blood components of Yougui Yin in normal rats and rats with kidney deficiency caused by adenine based on UPLC-MS technology].

Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.

[Study on oral absorption mechanisms of puerarin in nanocrystals self-stabilized pickering emulsion].

Nanocrystals self-stabilized Pickering emulsion(NSSPE) is a new kind of emulsion where only nanocrystals of poorly soluble drugs are used as stabilizers. Our previous study showed that NSSPE with Ligusticum chuanxiong oil as the main oil phase can significantly promote oral absorption of puerarin. The present study aimed to explore its absorption mechanism in oral administration. The in vitro dissolution test was carried out to study the effect of NSSPE on release of puerarin. The effects and mechanism of NSSPE on uptake and transport of puerarin across Caco-2 cell were investigated. The results showed that the drug release rate of NSSPE was similar to that of nanocrystals, with their cumulative dissolution of puerarin not affected by pH of releasing mediums, both significantly higher than that of crude material. The uptake of puerarin in NSSPE was concentration-dependent and significantly higher than that of solution or surfactant stabilized emulsion. Genistein and indomethacin, inhibitors of lipid rafts/caveolin, could significantly reduce the uptake of puerarin in NSSPE. Compared with solution, NSSPE and surfactants stabilized emulsion obviously increased transport rate K_a and apparent permeability coefficient P_(app) of puerarin in AP → BL direction, but there was no significant difference in BL → AP direction. It could be inferred that there were both passive and active transport mechanisms, as well as lipid raft/caveolin mediated endocytosis for absorption of NSSPE. The promoted oral absorption of puerarin in NSSPE was mainly related to the existing nanocrystal form which could promote dissolution, puerarin as well as Ligusticum chuanxiong oil which could promote drug transmembrane transport and inhibit drug efflux. It is the unique structure and composition of the compound NSSPE that promoted the oral absorption of puerarin.

[Intestinal absorption of puerarin nanocrystalline self-stabilizing pickering emulsion in rats].

To study the intestinal absorption characteristics of drug's nanocrystalline self-stabilizing Pickering emulsion (NSSPE) in situ in rats. Rat single-pass intestinal perfusion model was established, and high performance liquid chromatography (HPLC) was used to detect the concentration of puerarin in rat intestinal perfusion solution, assay the absorption rate constant (Ka) and the intestinal apparent permeability coefficient (Papp) of NSSPE in duodenum, jejunum, ileum, and colon, which were compared with those of raw material, nanocrystal and normal emulsion, respectively. For NSSPE, the Ka and Papp values were in the following order: duodenum>jejunum>ileum (P<0.05)>colon (P<0.01). However, there was no obvious difference between jejunum and ileum. As compared with raw material, nanocrystal and normal emulsion, the Ka and Papp values of NSSPE in duodenum were significantly higher than those of other three preparations (P<0.05); and the Ka and Papp values of NSSPE in jejunum and colon were significantly higher than those of raw material, nanocrystal and normal emulsion (P<0.01); and the Ka and Papp of NSSPE in ileum were also higher than those of raw material and normal emulsion (P<0.05), but had no obvious difference with nanocrystal. The results showed that NSSPE could significantly improve the absorption of puerarin in the intestine of rats.

[Effects of drug-oil properties on fabrication of drug nanocrystalline self-stabilizied Pickering emulsions].

To investigate the effects of drug and oil properties on the formation and stability of drug nanocrystalline self-stabilizied Pickering emulsions (NSSPE). Three insoluble Chinese medicine components (puerarin, tanshinone ⅡA and ferulic acid) were selected as model drugs, and Capmul C8, Fabrafil M 1944 CS, isopropyl myristate, Pzechwan Lovage Rhizome oil, and olive oil were used as oil phase. NSSPEs were developed by high pressure homogenization method and were evaluated for their appearance, centrifugal stability, droplet size and drug content changes in emulsion layer after storing at room temperature for 14 d. Then the properties of the oil (surface tension and viscosity) and properties of the drugs (surface energy, oil-water partition coefficient, size and Zeta potential of nanocrystalline and drug-water-oil contact angle) on the formation and stability of NSSPE were analyzed. The emulsification property and stability of five samples prepared with ferulic acid nanocrystals and different oils were significantly lower than those of puerarin and tanshinone ⅡA; the particle size of ferulic acid nanocrystals was 3.90 µm, extremely higher than 305 nm of puerarin and 406 nm of tanshinone ⅡA (P<0.05); the zeta potential of ferulic acid nanocrystals was -0.018 0 mV, significantly lower than －29.1 mV of puerarin and -42.6 mV of tanshinone ⅡA (P<0.05). Three samples prepared with isopropyl myristate and different drugs were not emulsions and the viscosity of isopropyl myristate was 4.67 mPa•s, significantly lower than that of the other oils (P<0.01). Puerarin-NSSPEs prepared with Pzechwan Lovage Rhizome oil showed best emulsification property and stability; the contact angle of puerarin in Pzechwan Lovage Rhizome oil-water was 69.7°, close to 90°, significantly higher than other contact angles. NSSPEs made by tanshinone ⅡA-Capmul C8-water, tanshinone ⅡA-Labrafil M 1944 CS-water showed highest stability, with a contact angle of 99.2° and 112° respectively, more close to 90° than other oils. The results indicated that viscosity, size and Zeta potential of nanocrystalline and three-phase contact angle had great influence on the formation and stability of NSSPE; surface tension of oil, surface energy of drug and oil-water partition coefficient may not be related to the construction of NSSPE.

[Stability optimization of puerarin nanocrystalline self-stabilizied Pickering emulsion by response surface methodology].

A new Pickering emulsion, puerarin nanocrystalline self-stabilized Pickering emulsion (Pu-NSSPE) was developed. Box-Behnken design was used for optimizing the preparation formulation of Pu-NSSPE to improve its stability, and the effects of concentration of puerarin, volume ratio of water to oil, and pH value of water phase on the stratification index of emulsion, droplet size and drug concentration in emulsion were investigated. Results showed that the optimized Pu-NSSPE could be prepared with the concentration of puerarin of 0.5%, the volume ratio of water to oil of 9∶1 and the pH of water of 9. The size of emulsion droplet of optimized Pu-NSSPE was (12.70±1.17) µm and the drug content was (4.49±0.21) g•L⁻¹. The above indexes had no significant changes within the storage of 6 months at room temperature, indicating good stability. Microstructure characterizations by scanning electron micrograph, confocal laser scanning microscope and fluorescence microscope showed that the optimized Pu-NSSPE had a stable core-shell structure of emulsion droplet formed by the adsorption of puerarin nanocrystallines at the surface of oil droplets, which may be the microstructure reason for the long stability of Pu-NSSPE.

[Effect factors and mechanisms of borneol's bidirectional regulation on blood-brain barrier permeability].

In recent twenty years, there are a lot of studies about the effect of borneol on permeability of blood-brain barrier(BBB); however, it isDODOrt of regular conclusions of effect factors and in-depth analysis of functional mechanisms. The current researching data were collected and analyzed in this paper for illuminating the effect factors and mechanisms of borneol on permeability of BBB.The following conclusions were obtained: five factors about borneol influencing the permeability of BBB. First, opticity activity of borneol had no significant effect on action effects. Second, dose of borneol in the range of 50.00-200.00 mg•kg⁻¹, did not affect the effect direction, but only affect its action intensity either with use alone or combination use. Third, the borneol can increase the permeability of physiological BBB, and decrease the permeability of pathological BBB. Fourth, regardless of using singly or using compatibility with musk, borneol can decrease the permeability of BBB in different brain disease models. Fifth, when used with astragalus, catalpol or puerarin, borneol can increase the permeability of BBB and promote the drugs through BBB in pathological conditions. The target spots and mechanisms of borneol's bidirectional regulation on the permeability of BBB are related to the structure and function of cerebral endothelial cells, the exocytosis effects of P-gp and low pinocytosis internal transport effects. On one hand，borneol can down-regulate P-gp by inhibiting NF-κB to reduce the exocytosis effects of P-gp and promote the blood brain barrier pinocytosis to increase the permeability of BBB; On the other hand，borneol can reduce the degradation of basement membrane of blood vessel and tight junctions by inhibiting the expression of IL-1ß, MMP-9 to decrease the permeability of BBB；moreover，borneol has bidirectional regulation effects on blood-brain barrier permeability by influencing the signaling pathways of Ca2+-eNOS-NO, VEGF-eNOS-NO. However, the detailed mechanisms that borneol regulates and controls the permeability of BBB are so complicated, so they shall be further proved and clarified.

[Preparation and evaluation of silybin nanocrystallines self-stabilizing Pickering emulsion].

A new silybin nanocrystallines self-stabilizing Pickering emulsion(SN-SSPE) was developed using the high pressure homogenization method to improve the oral bioavailability of silybin. The influences of homogenization pressure from 50 to 120 MPa and drug content from 100 mg to 1000 mg on the formation of SN-SSPE were studied. The morphology, structure and size of emulsion droplet in SN-SSPE were characterized using scanning electron micrograph and confocal laser scanning microscope.SN-SSPE was evaluated, including stability, in vitro release and in vivo oral bioavailability. The particle size of silybin nanocrystallines (SN-NC) was decreased as the pressure increased until 100 MPa. When the drug content reached 300 mg or above, stable SN-SSPE was formed from sufficient SN-NC covering surfaces of oil droplets completely. The emulsion droplet of SN-SSPE with the size of 27.3 ± 3.1 µm showed a core-shell structure consisting of oil droplet as core and SN-NC as shell.SN-SSPE showed a high stability over 40 days. In vitro release rate of SN-SSPE was faster than silybin coarse powder and similar to silybin nanocrystallines suspension(SN-NCS).After intragastric administration in rats, the peak concentration of SN-SSPE was increased by 2.5-fold and 2.3-fold compared with SN-NCS and silybin coarse powder, respectively. The AUC of SN-SSPE was increased by 1.4-fold and 3.8-fold compared with SN-NCS and silybin coarse powder, respectively. All these results showed that nanocrystallines of the poorly soluble drug could stabilize Pickering emulsions, which provides a promising application to the improvement of the oral bioavailability of poorly soluble drugs.

[In vitro inhibitory effects of Jiawei Foshou San capsule on activity of cytochrome P450 enzymes in rat and human liver microsomes].

This study was designed to investigate the inhibitory effects of Jiawei Foshou San (JWFSS) capsule in vitro on five major human liver microsomes CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, as well as on rat liver microsomes CYP1A2, CYP2C9, CYP2D2, CYP2E1, CYP3A1/2. The test groups included a negative control group, an inhibitor positive control group, an ferulic acid (FA) group, a ligustrazine (LZ) group, a tetrahydropalmatine (THP) group, and an JWFSS capsule group. After incubating the liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS, and IC(50) values were calculated to assess the inhibitory effect of JWFSS capsule and its components on five rat/human CYP450 enzymes. All of the IC(50) values for the FA and the LZ for the five CYPs could not be determined. The IC(50) of the THP for rat CYP3A1/2 and for human CYP2D6 was 7.46 and 9.24 µmol·L(-1), respectively. The IC(50) of the JWFSS capsule for rat CYP2D2, CYP2E1 and CYP3A1/2 was 241.3, 369.8 and 293.0 mg·L(-1), for human CYP2D6, CYP2E1 and CYP3A4 was 123.9, 189.9 and 171.3 mg·L(-1) respectively. The results indicated there were little probability that FA and LZ inhibited the activity of rat and human liver five CYPs; THP was identified as moderate-intensity inhibitor of rat liver CYP3A1/2 and human liver CYP2D6; JWFSS capsule might have a inhibitory effect on the activity of rat and human liver CYP2D, CYP2E1 and CYP3A in vitro, showing that there was a strengthened efficacy and a prolonged effective time for drugs metabolized by CYP2D, CYP2E1, CYP3A and combined with JWFSS capsule.

[Effects of different preparation technologies on concentrations of puerarin and catalpol in plasma and brain of rats after oral administration].

To compare the effects of different preparation technologies on the concentrations of puerarin and catalpol in plasma and brain of rats after oral administration, in order to lay an experimental basis for developing new oral Zige preparations. The nanocrystal, self-microemulsions (tween-80 and Cremophor RH-40 as emulsifiers) and inclusion complex of HP-ß-CD containing puerarin and catalpol were prepared. The concentrations of puerarin and catalpol in plasma and brain of rats after oral administration were determined by HPLC-MS/MS method. The pharmacokinetic parameters and brain target index were compared. The results showed that preparation technologies had different influences on the concentrations of puerarin and catalpol in plasma and brain. The self-microemulsion (tween-80) could significantly increase the oral absorption of puerarin than other technologies(P<0.05), and inclusion complex could remarkably increase the oral absorption of catalpol than nanocrystal(P<0.01). For puerarin, the brain targeting index of inclusion complex was the highest (P<0.05); but for catalpol, the brain targeting index of inclusion complex and self-microemulsions were both higher than nanocrystal (P<0.05). The self-microemulsion(tween-80) had the highest AUCbrain of puerarin than other groups (P<0.01); the inclusion complex had the highest AUCbrain for catalpol, but there was no significant difference compared with self-microemulsions. In conclusion, the self-microemulsion (tween-80) technology could increase the amount of puerarin and catalpol in brain, and was expected to be used in new oral Zige preparations.

[Borneol promotes oral absorption and penetration into brain of puerarin and catalpol].

To investigate the effect of borneol on the oral absorption and penetration into brain of puerarin and catalpol from cell level and animal level, and screen the concentration of borneol that is suitable for Zige compound oral preparation. Blood-brain barrier(BBB) model was established by co-culture of primary brain microvessel endothelial cells(BMEC) and astrocytes(As) in rats, and it was used to investigate the effect of borneol(concentration from 6.25 to 100 mg•L⁻¹) on the transport of puerarin and catalpol. The pharmacokinetics of puerarin and catalpol in plasma and brain of rats were compared after intragastric administration of borneol solution (0, 25, 50 and 100 mg•kg⁻¹) immediately followed by puerarin(200 mg•kg⁻¹) and catalpol(45 mg•kg⁻¹) nanocrystal suspension. Barrier function was basically formed after co-culturing of brain microvascular endothelial cells and astrocytes for 7 d. The permeability of puerarin and catalpol across blood-brain barrier was increased significantly(P<0.05) and transendothelial electrical resistance(TEER) values at 2 h were decreased significantly(P<0.01) when the concentration of borneol was between 12.5 to 100 mg•L⁻¹ as compared with the control group. Borneol at the dose of 50 mg•kg⁻¹ and 100 mg•kg⁻¹ could significantly increase the oral absorption of puerarin(P<0.05), but there was no obvious effect for catalpol. AUCbrain/AUCblood for puerarin was highest with borneol at dose of 100 mg•kg⁻¹ (P<0.05), while AUCbrain/AUCblood for catalpol was highest with borneol at dose of 50 mg•kg⁻¹ (P<0.05). AUCbrain was highest at 100 mg•kg⁻¹ for puerarin(P<0.05); while for catapol, it was highest at 50 mg•kg⁻¹, but it was not significantly different from 100 mg•kg⁻¹. In conclusion, borneol could increase the amount of puerarin and catalpol in brain after oral administration and the optimized dose shall be 100 mg•kg⁻¹.

[Effect of Jiawei Foshou San and its compatibility on hepatic P450 enzyme activity and hepatocyte morphology in rats].

To investigate the effect of Jiawei Foshou San and its various combined administration on hepatic P450 enzyme activity and hepatocyte morphology in rats. Rats were orally administered with drugs for four weeks and then sacrificed to prepare liver microsomes. The liver microsomes were incubated with the cocktail method; The metabolites were determined with the rapid liquid chromatography with tandem mass spectrometry (LC-MS/MS) to investigate the hepatocyte P450 enzyme activity. In addition, the hepatic pathological changes were observed by using the hematoxylin and eosin (HE) staining. Compared with the control group, the enzyme activity of CYP1A2 and CYP3A4 in the Jiawei Foshou san group showed a significant rise (P < 0.05); the enzyme activity of CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in the ferulic acid + ligustrazine group and the ligustrazine + tetrahydropalmatine group showed a significant rise (P < 0.05) ; the enzyme activity of CYP1A2, CYP2D6 and CYP2E1 in the ligustrazine group showed a significant rise (P < 0.05); the enzyme activity of CYP3A4 in the ferulic acid group showed a significant reduction (P < 0.05). After the administration with various drugs, the hepatocyte morphologies in the ferulic acid group and the ligustrazine group were normal. The pathological changes were observed in the tetrahydropalmatine group, such as unclear boundary of hepatic lobules, disordered hepatic cell arrangement, blurred edge, anisokaryosis and infiltration of inflammatory cells. The ferulic acid + tetrahydropalmatine group, the ligustrazine + tetrahydropalmatine group and the Jiawei Foshou San group also showed inflammatory infiltration, but with less pathological changes, particularly the Jiawei Foshou San group. The study result shows that Jiawei Foshou San can induce the enzyme activity of CYP1A2 and CYP3A4, and ligustrazine may be the effective substance for inducing CYP1A2. Its combination with ferulic acid and ligustrazine can significantly reduce the liver toxicity of tetrahydropalmatine.

[Impact of drug molecules on HP-ß-CD compound inclusion].

To study the interaction of drugs of different properties, namely puerarin, borneol and catalpol in the process of in- clusion, in order to explore the inclusion regularity of multi-component and multi-property traditional Chinese medicine compound in- clusions. With HP-ß-CD as the inclusion material, the freeze-drying method was used to prepare the inclusion. The inclusion between puerarin, borneol and catalpol was tested by measuring the inclusion concentration, DSC and X-ray diffraction. According to the find- ings, when insoluble drugs puerarin and borneol were included simultaneously, and puerarin was overdosed, puerarin included was almost equal to puerarin included, and borneol was not included. When puerarin was under-dosed, and HP-ß-CD was overdosed, borne- ol was included, and the simultaneous inclusion was lower than the separate inclusion of borneol. When water-soluble drug catalpol was jointly included with puerarin or borneol, the simultaneous inclusion was almost the same with their separate inclusion, without charac- teristic peak of catalpol in DSC and X-ray diffraction patterns. There is a competition in the simultaneous inclusion between water-solu- ble drugs puerarin and borneol and a stronger competition in puerarin. The water-soluble drug catalpol could be included with HP-ß-CD with no impact on the inclusion of puerarin or borneol.

Effect of Morinda officinalis capsule on osteoporosis in ovariectomized rats.

AIM: To explore the therapeutic effects of Morinda officinalis capsules (MOP) on osteoporosis in ovariectomized rats. METHODS: Six-month-old female Sprague-Dawley rats were induced for postmenopausal osteoporosis (PMOP) by bilateral ovariectomy and divided into seven groups as follows: sham-operated group, ovariectomized (OVX) control group, OVX treated with xianlinggubao (XLGB) (270 mg·kg⁻¹·d⁻¹), OVX treated with alendronate sodium (ALN) (3 mg·kg⁻¹·d⁻¹), and OVX treated with Morinda officinalis capsule (MOP) of graded doses (90, 270 and 810 mg·kg⁻¹·d⁻¹) groups. Oral treatments were administered daily on the 4(th) week after ovariectomy and lasted for 12 weeks. The bone mineral density was evaluated by dual-energy X-ray absorptiometry. The tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (AKP), and osteocalcin (OC) levels in the serum and plasma were determined by standard colorimetric and enzyme immunoassays methods. Bone biomechanical properties and morphological parameters were analyzed by three-point bending test and histomorphometry respectively. RESULTS: Morinda officinalis capsules at all doses were able to significantly prevent the OVX-induced loss of bone mass due to diminishing serum AKP and TRAP levels while elevating OC level in the plasma. Morinda officinalis capsules also enhanced the bone strength and prevented the deterioration of trabecular microarchitecture. CONCLUSION: Morinda officinalis capsules possess potent anti-osteoporotic activity in OVX rats which could be an effective treatment for postmenopausal osteoporosis.

[Comparison of preparing two polylactide nanoparticles loaded lipophilic anti-cancer herb drug by nanoprecipitation method].

This paper introduced an experimental study of polylacticacid (PLA) nanoparticles of lipophilic anti-cancer herb drug using a precipitation method. Cucurbitacins (Cu) and Curcuminoids (Cur) were selected to be model drugs. They had similar solubility but their incorporation effects were significantly different: the average drug entrapment ratio, the average drug loading and the average drug recovery were 38.53%, 2.21% and 27.02% respectively; while those of Cur-PLA-NP were 94.36%, 14.35% and 91.23% respectively. To analyse the reason, drug incorporation process was investigated. By measuring solvent evaporation rate, ratio of drug PLA precipitates, drug distribution in system and entrapping ratio at different time of preparation, we found the difference of precipitation velocity of drug was the main reason. We also concluded that not all lipophilic drug can be well entrapped into PLA nanoparticle by nanoprecipitation method. The drug incorporation depended on the interations among drug, PLA and organic solvents, in addition to the solubility of the drug.

[Studies on the optimized extraction technology of Paeonia suffruticosa].

OBJECTIVE: To obtain the optimized extraction technology of Paeonia suffruticosa by comparing several extraction method. METHOD: Extract P. suffruticosa by ethanol circumfluence, distillation-decoction, CO2-SFE and traditional decoction, and analyse the results according to the total extraction rate, extraction rate of paeono, extraction of other ingredients and production feasibility. RESULT: Total extraction rates of which are 12.66%, 13.51%, 7.28%, 7.56% respectively; extraction rates of paeonol are 2.45%, 2.26%, 0.31%, 1.15% in turn; Phenolic glycosides can be extracted by ethanol circumfluence, distillation-decoction, traditional decoction, but not by CO2-SFE. CONCLUSION: Distillation-decoction is the most proper extraction technology of P. suffuticosa at present.

[The preparation of the polylacticacid nanoparticles of cucurbitacin and their drug loading].

This paper introduced an experimental study of the preparation of polylacticacid (PLA) nanoparticles of cucurbitacin (CuC) using a precipitation method. The residual acetone, ratio of CuC PLA precipitates, and the relationships between the ratios of two precipitates and drug incorporation rates were measured. It appeared that the nanoparticles with 60% of PLA incorporated with 5.5% of CuC were formed when acetone was injected into the aqueous phase. As the acetone gradually evaporated, drug incorporation/encapsulation continued, with most of CuC (about 70%) formed new crystalline cores and suspended in the form of microcrystals in the medium, resulting a suspension containing both nanoparticles and microcrystals. We also concluded that this system may not necessarily be suitable for all lipophilic drugs to be prepared to PLA nanoparticles with good incorporation rate. The drug incorporation depended on the interactions among drug, PLA, and organic solvents, in addition to the solubility of the drug.