[Research progress on liposome and nanomicelle targeted drug delivery system across blood-brain barrier].

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.

Preparation, in vitro and in vivo Evaluation of Thermosensitive in situ Gel Loaded with Ibuprofen-Solid Lipid Nanoparticles for Rectal Delivery.

Background: Ibuprofen (IBU), a nonsteroidal anti-inflammatory drug, shows poor gastrointestinal absorption due to its low solubility, which limits its clinical application. Objective: In the present study, we aimed to develop thermosensitive gel-mediated ibuprofen-solid lipid nanoparticles (IBU-SLN-ISG) to improve the dissolution and bioavailability of IBU after rectal delivery. Methods: IBU-loaded SLNs (IBU-SLNs) were developed and optimized applying Box-Behnken design. The optimized IBU-SLNs were characterized by physicochemical parameters and morphology. Then, the optimized IBU-SLNs was incorporated into the gel and characterized for gel properties and rheology and investigated its release in vitro, pharmacokinetics in vivo, rectal irritation and rectal retention time. Results: The optimized SLNs had an EE of 90.74 ± 1.40%, DL of 11.36 ± 1.20%, MPS of 166.77 ± 2.26 nm, PDI of 0.27 ± 0.08, and ZP of -21.00 ± 0.59 mV. The FTIR spectra confirmed successful encapsulation of the drug inside the nanoparticle as only peaks responsible for the lipid could be identified. This corroborated well with XRD spectra, which showed a completely amorphous state of the IBU-SLNs as compared to the crystalline nature of the pure drug. The gelation temperature of the prepared IBU-SLN-ISG was 33.30 ± 0.78°C, the gelation time was 14.67 ± 2.52 s, the gel strength was 54.00 ± 1.41 s, and the mucoadhesion was (11.54±0.37) × 102dyne/cm2. The in vitro results of IBU-SLNs and IBU-SLN-ISG showed a biphasic release pattern with initial burst release followed by sustained release. More importantly, IBU-SLN-ISG produced much better absorption of IBU and improved bioavailability in rats. In addition, IBU-SLN-ISG caused no irritation or damage to rectal tissues, and could be retained in the rectum for a long time. Conclusion: Thermosensitive in situ gel loaded with IBU-solid lipid nanoparticles might be further developed as a more convenient and effective rectal dosage form.

Pharmacokinetics of five phthalides in volatile oil of Ligusticum sinense Oliv.cv. Chaxiong, and comparison study on physicochemistry and pharmacokinetics after being formulated into solid dispersion and inclusion compound.

BACKGROUNDS: The dried rhizome of Ligusticum sinense Oliv.cv. Chaxiong has been used to treat cardiovascular and cerebrovascular diseases, atherosclerosis, anemia and stroke. A high purity extract from chaxiong (VOC, brownish yellow oil) was extracted and separated. Its main components were senkyunolide A (SA, 33.81%), N-butylphthalide (NBP, 1.38%), Neocnidilide (NOL, 16.53%), Z-ligustilide (ZL, 38.36%), and butenyl phthalide (BP, 2.48%), respectively. Little is known about the pharmacokinetics of these phthalides in Chaxiong, and different preparations to improve the physicochemistry and pharmacokinetics of VOC have not been investigated. METHODS: At different predetermined time points after oral administration or intravenous administration, the concentrations of SA, NBP, NOL, ZL and BP in the rat plasma were determined using LC-MS/MS, and the main PK parameters were investigated. VOC-P188 solid dispersion and VOC-ß-CD inclusion compound were prepared by melting solvent method and grinding method, respectively. Moreover, the physicochemical properties, dissolution and pharmacokinetics of VOC-P188 solid dispersion and VOC-ß-CD inclusion compound in rats were assessed in comparison to VOC. RESULTS: The absorptions of SA, NBP, NOL, ZL and BP in VOC were rapid after oral administration, and the absolute bioavailability was less than 25%. After the two preparations were prepared, dissolution rate was improved at pH 5.8 phosphate buffer solution. Comparing VOC and physical mixture with the solid dispersion and inclusion compound, it was observed differences occurred in the chemical composition, thermal stability, and morphology. Both VOC-P188 solid dispersion and VOC-ß-CD inclusion compound had a significantly higher AUC and longer MRT in comparison with VOC. CONCLUSION: SA, NBP, NOL, ZL and BP in VOC from chaxiong possessed poor absolute oral bioavailability. Both VOC-P188 solid dispersion and VOC-ß-CD inclusion compound could be prospective means for improving oral bioavailability of SA, NBP, NOL, ZL and BP in VOC.

[Pharmacokinetic study on five components in phthalide target areas of Chaxiong and its ß-CD inclusion compounds based on UPLC-MS/MS].

This study aims to establish a method for the determination of the concentration of five main components of phthalide target areas of Chaxiong(CPTA) and its inclusion of ß-CD in the plasma of rats, and determine the pharmacokinetic parameters, absolute bioavailability and relative bioavailability of CPTA/ß-CD inclusion compound in vivo. The plasma concentrations of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide were determined with UPLC-MS/MS. The content determination was conducted at the chromatographic conditions as follows: Shim-pack GIST C_(18)-AQ HP column(2.1 mm×100 mm, 3 µm), mobile phase of 0.1% formic acid solution(A)-acetonitrile(B), gradient elution, flow rate of 0.3 mL·min~(-1), column temperature of 35 ℃ and injection volume of 2 µL. The mass spectra were obtained with electrospray ion source(ESI), positive ion mode and multi reaction monitoring. CPTA/ß-CD inclusion compound was prepared by grinding method, DAS 2.0 software was used to model the data, and the absolute bioavailability of CPTA and relative bioavailability of inclusion compound were calculated. Finally, the methods for the determination of five components of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide in CPTA, were successfully established. The linear relationship among the five components was good within their respective ranges, r>0.99. The absolute bioavailability of the five components in rats was 22.30%, 16.32%, 21.90%, 10.16% and 12.43%, respectively. After CPTA/ß-CD inclusion was prepared, the relative bioavailability of the five components was 138.69%, 198.39%, 218.01%, 224.54% and 363.55%, respectively, significantly improved. This method is rapid, accurate and sensitive, so it is suitable for the pharmacokinetic study of extracts in traditional Chinese medicine and their preparations.

[Effect and mechanism of total flavonoids of Lichi Semen on CCl_4-induced liver fibrosis in rats, and prediction of Q-marker].

This paper was to investigate the effect of total flavonoids of Lichi Semen(TFL) on carbon tetrachloride(CCl_4)-induced liver fibrosis in rats, analyze and predict its mechanism of action and potential quality markers(Q-marker). Firstly, male SD rats were taken and injected subcutaneously with a 40% CCl_4-vegetable oil solution twice a week for 8 consecutive weeks to establish a rat model of liver fibrosis. The rats with liver fibrosis were randomly divided into model group, silybin group(43.19 mg·kg~(-1)), Fuzheng Huayu Capsules group(462.75 mg·kg~(-1)), and TFL groups(100 mg·kg~(-1) and 25 mg·kg~(-1)), with normal rats as a blank group, 10 rats in each group. Except for the blank group, the rats in the other groups were subcutaneously injected with 40% CCl_4-vegetable oil solution of a maintenance dose, once a week. The rats in various treatment groups received corresponding doses of drugs, while the rats in the blank group and model group received the same volume of normal saline once a day for 4 weeks. At the end of the experiment, blood was collected from the abdominal aorta and the liver tissues were collected. The levels of total bilirubin(TBiL), direct bilirubin(DBiL), indirect bilirubin(IBiL), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum were detected by using an automatic biochemical detector. Masson staining was used to observe the histopathological changes of rat liver. Then, the chemical compositions of TFL were collected, and the action targets of these chemical compositions were predicted through SWISS database and reverse molecular docking server(DRAR-CPI). After screening of disease targets of liver fibrosis by Gene Cards database, the protein-protein interaction was analyzed with use of STRING database, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) enrich analysis were also carried out. Moreover, an iTRAQ proteomics technology was used to determine protein expression in liver tissues of rats in TFL, model and blank groups to verify the targets. Furthermore, Cytoscape software was used to establish and visualize the network of chemical components, targets and pathways, and predict the potential Q-marker of TFL. The results showed that the levels of TBiL, DBiL, IBiL, ALT, and AST in the model group were significantly higher than those in the blank normal group(P<0.05), and the above levels in the treatment groups were lower than those in the model group, but with no significant differences. Masson staining showed that the liver damage and the degree of fibrosis were severe in the model group, and were relieved to different degrees in the treatment groups. Then, 74 chemical components were screened, which could act on 865 targets such as EGFR and SRC, participating in the regulation of cancer pathways, PI3 K-Akt signaling pathway, HIF-1 signaling pathway and other signaling pathways closely related to liver fibrosis. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin showed the highest correlation with liver fibrosis-related targets and pathways. Proteomics results showed that a total of 18 proteins among the 45 proteins predicted by internet pharmacology were identified, among which 6 proteins were significantly expressed, including 5 up-regulated proteins and 1 down-regulated protein. The protein expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1 was significantly returned to a normal state in the TFL treatment groups. In conclusion, TFL may demonstrate the anti-hepatic fibrosis and potential hepatoprotective effects by regulating the expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1, which may be associated with the regulation of multiple signaling pathways related to liver fibrosis such as PI3 K-Akt pathway. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin could be regarded as potential Q-markers of TFL for quality control.

Dihydrotanshinone exhibits an anti-inflammatory effect in vitro and in vivo through blocking TLR4 dimerization.

Dihydrotanshinone (DHT), one of the major ingredients of Salvia miltiorrhiza Bunge (Danshen), displays many bioactivities. However, the activity and underlying mechanism of DHT in anti-inflammation have not yet been elucidated. In this study, we investigated the anti-inflammatory activity and molecular mechanism of action of DHT both in vitro and in vivo. Our data showed that DHT significantly decreased the release of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, THP-1 cells, and bone marrow-derived macrophages (BMDMs), and altered the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, flow cytometry results indicated that DHT reduced the calcium influx, and generation of reactive oxygen species (ROS), and nitric oxide (NO) generation in LPS-stimulated RAW264.7 cells. Moreover, DHT suppressed the transcription of nuclear factor-κB (NF-κB), the expressions of NF-κB proteins, and nuclear translocation of NF-κB/p65, thereby suggesting that the NF-κB pathway played a role in the anti-inflammatory action of DHT. In addition, DHT attenuated LPS-challenged activator protein-1 (AP-1) activity, resulting from interference of the mitogen-activated protein kinase (MAPK) pathway. The molecular docking simulation of DHT to toll-like receptor 4 (TLR4) suggested that DHT binds to the active sites of TLR4 to block TLR4 dimerization, which was further corroborated by cellular thermal shift assay and co-immunoprecipitation (Co-IP) experiments. Furthermore, the recruitment of myeloid differentiation primary response gene 88 (MyD88) and the expression of transforming growth factor-b (TGF-b)-activated kinase 1 (p-TAK1) were disturbed by the inhibition of TLR4 dimerization. Thus, investigating the molecular mechanism of DHT indicated that TLR4-MyD88-NF-κB/MAPK signaling cascades were involved in the anti-inflammatory activity of DHT in vitro. In in vivo mouse models, DHT significantly ameliorated LPS-challenged acute kidney injury, inhibited dimethylbenzene-induced mouse ear oedema, and rescued LPS-induced sepsis in mice. Taken together, our results indicated that DHT exhibited significant anti-inflammatory activity both in vitro and in vivo, suggesting that DHT may be a potential therapeutic agent for inflammatory diseases.

[Development and characterization of TPGS modified proniosomes of docetaxel].

A novel oral delivery system that TPGS modified docetaxel proniosomes, DTX-TPGS-PN, was developed and the characterization after hydration was observed. Firstly, Doce-TPGS-PN was optimized by investing the factors, including the type of surfactant, methods of adding TPGS, content of TPGS and the molar ratio of span40/cholesterol, which may affecting the particle size, encapsulation efficiency and instantaneous release of drug in the formulation. Then, the morphology, particle size, Zeta potential, encapsulation efficiency and in vitro release of the formulation were evaluated. The result showed that hydrated nanoparticles of DTX-TPGS-PNs were (93 ± 6.5) nm in size,(-83.95 ± 3.69) mV in zeta potential, (97.31 ± 0.60)% in encapsulation efficiency, exhibiting spherical morphology and biphasic release process that a low burst effect within the first 0.5 hour and a relative-sustained release for the next several hours in PBS. These results indicate the oral delivery system of DTX-TPGS-PN was successfully built with good properties.

[Progress in regulation effect of aromatic refreshing traditional Chinese medicine on BBB permeability and its mechanism].

The blood-brain barrier (BBB) protects the brain against unwanted substances, while, at the same time, limits the transport of many drugs into the brain. Aromatic refreshing traditional Chinese medicine (TCM) can induce resuscitation and modify the permeability of BBB, promoting other drugs entering into the brain with brain protection effect. This paper mainly reviews the research progress in regulation effects and mechanism of usual aromatic refreshing TCM, such as borneol, moschus, styrax, benzoinum and Tatarinow Sweetflag Rhizome, on BBB permeability. To broaden the application of these drugs in modern pharmaceutics in the future, the relatively research should emphasis on combining aromatic refreshing TCM with new formulations and technologies in pharmaceutics, providing novel promising strategies for brain diseases therapy.

miR-1303 targets claudin-18 gene to modulate proliferation and invasion of gastric cancer cells.

BACKGROUND: MicroRNAs have emerged as important gene regulators and are recognized as important molecules in carcinogenesis. However, the effects of microRNA-1303 (miR-1303) on gastric cancer (GC) cells and the upstream regulation of GC-associated claudin-18 gene (CLDN18) remain unclear. miR-1303 may be involved in the tumorigenesis of GC by targeting CLDN18. AIMS: The purpose of this study was to explore the effect of miR-1303 targeting of CLDN18 on the proliferation, migration and invasion of human GC cells. METHODS: The expression of miR-1303 and claudin-18 in GC tissues and gastric cancer cell lines were detected by qRT-PCR and western blotting, respectively. CCK8 and colony formation assays were performed to study the influence of miR-1303 on the proliferation of the GC cell lines. Transwell and wound-healing assays were carried out to investigate the effect of miR-1303 on the invasion and migration of GC cell lines. Luciferase reporter assays, restore assays and western blotting were used to demonstrate whether CLDN18 is a direct target of miR-1303. RESULTS: miR-1303 was significantly overexpressed whereas claudin-18 was downregulated in GC tissues and cell lines, which was significantly associated with tumor size, location invasion, histologic type and tumor-node-metastasis stage. Cell proliferation rates were reduced, and cell invasion and migratory ability was significantly restricted in miR-1303 inhibitor-transfected groups. miR-1303 could bind to the putative binding sites in CLDN18 mRNA 3'-UTR and visibly lower the expression of claudin-18. The introduction of claudin-18 without 3'-UTR restored the miR-1303 promoting migration function. CONCLUSIONS: Downregulation of miR-1303 can inhibit proliferation, migration and invasion of GC cells by targeting CLDN18.

[Effect of Cornus officinalis fruit core extract on the cardiac hypertrophy induced by two kidney two clip].

OBJECTIVE: To observe the effect of Cornus officinalis fruit core extract on cardiac hypertrophy induced by two kidney two clip (2K2C) and its mechanism. METHODS: Male Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group, model group and treatment groups (300, 600 mg/kg). Rats were intragastric administered medicine for 4 weeks from the fourth week after surgery. Sham-operated and 2K2C rats were given vehicle for 4 weeks. Blood pressure and hemodynamic parameters were measured. Left ventricular weight to body weight (LVM/BM) ratio was calculated. Paraffin-embedded hearts were cut into 5 microm slices, which were stained with hematoxylin-eosin (HE) and Masson for morphological analysis; Western-blot analysis was performed to investigate the effects of Cornus officinalis fruit core extract on the expression of P47phox, Nox4 in myocardium. RESULTS: Compared with sham-operated group, the blood pressure and LVM/BM ratios were markedly elevated in model groups. Meanwhile cardiomyocyte cross sectional areas was markedly increased and myocardial fibers showed disordered arrangement while these parameters were markedly reversed after treatment with Cornus officinalis fruit core extract for 4 weeks. At 8th weeks after operation, model rats developed obvious LV hypertrophy. Cornus officinalis fruit core extract, more significant in high dose, decreased the blood pressure and LVM/BM ratios and reversed the cardiomyocyte hypertrophy and myocardial fibrosis. Moreover, Cornus officinalis fruit core extract decreased the expression of P47phox and Nox4 which elevated in LV in model rats. CONCLUSION: Cornus officinalis fruit core extract could significantly decrease the blood pressure, reverse cardiac hypertrophy and improve the function of heart which is possibly associated with the down-regulation of P47phox and Nox4.

[Acute pulmonary toxicity of rats caused by different sized SiO2 nanoparticles].

OBJECTIVE: To study the pulmonary toxicity to rats induced by different sized SiOz particles. METHODS: One hundred and five male SD rats were divided into seven groups randomly according to their weight. Experimental rats were exposed to 20, 50, 80, 140, 280 and 800 nm SiO2 particles at the dose of 400 mg/m3 by inhalation for 2 hours respectively. The control group was exposed without SiO2 particles. At the 24th, 48th, 72th hour after exposure, five rats were sacrificed at each time point and the total cellular scores, total protein, lactate dehydrogenase (LDH) in BALF and the histopathological changes in lungs were observed. RESULTS: The total cellular score, total protein and lactate dehydrogenase in bronchoalveolar lavage fluid (BALF) of all experimental groups were higher than the control group. Between 800 nm group and the control group, there were no significant changes in total cellular sare, total protein and LDH in BALF (P > 0.05). At 48 h, the total cellular score of 280 nm group had no significantly change compared with the control group, but the total protein and LDH in BALF of 280 nm group were significantly higher than the control group (P < 0.05). The total cellular score at 24 h and the total protein at 24, 48 h had no significantly changes compared with the control group, but other indexes of 140 nm group were significantly higher than the control group. All the indexes of the 20, 50, 80 nm group were significantly higher than the control group (P < 0.05), and higher than 800 nm group mostly time. The TCS, total protein and LDH in BALF increased firstly and then reduced. The experimental group visible part pulmonary alveolus gap varying degree proliferation accumulation, its periphery has massive phlogocyte accumulation,such as granular cells and macrophage. CONCLUSION: Under this condition ,the SiO2 particles can cause lung damage more serious with the smaller diameter SiO2 particles. As time going on, the damage caused by SiO2 particles is not so serious as before.

Polybrominated diphenyl ethers and their methoxylated metabolites in anchovy (Coilia sp.) from the Yangtze River Delta, China.

BACKGROUND, AIM, AND SCOPE: Polybrominated diphenyl ethers (PBDEs) and their metabolites are toxic to animals, and concentrations of the PBDEs metabolites can exceed those of the parent materials. But no information was available on concentrations of PBDEs metabolites in the lower Yangtze River in the region around Jiangsu Province of China, which is heavily urbanized and industrialized area. The aims of this study were to determine whether PBDEs and their methoxylated PBDEs (MeO-PBDEs) were accumulated in Coilia sp. in this area and to investigate the potential sources for these two kinds of brominated organic pollutants. MATERIALS AND METHODS: Samples of four species of anchovy were collected from eight sites in the lower Yangtze River, Taihu Lake, and Hongzehu Lake. Concentrations of 13 PBDEs congeners and eight methoxylated PBDEs were determined by use of organic solvent extraction, followed by gas chromatography and mass spectrometry. RESULTS AND DISCUSSION: The frequencies of detection for PBDEs and MeO-PBDEs were 92% and 53%, respectively. Concentrations of summation operatorPBDEs ranged from not detected (ND) to 77 ng/g lipids (ND-3.8 ng/g wet weight). Concentrations of summation operatorMeO-PBDEs in anchovy ranged from ND to 48 ng/g lipids (ND-8.2 ng/g wet weight). The PBDE concentrations in anchovy from the Yangtze River Delta were similar to or less than those reported for other species from other locations around the world, while the concentrations of MeO-PBDEs were comparable to or slightly less than those reported in other studies. This is the first report of MeO-PBDEs in biota of China. CONCLUSIONS: The results of this study as well as those of other studies suggest that PBDEs in anchovy are primarily of synthetic origin and released by human activities, while MeO-PBDEs in anchovy are primarily from nature as natural products from the sea instead of metabolism of PBDEs in anchovy.

[Determination of apparent aqueous solubility and apparent oil-water partition coefficients of three bufadienolides composition].

OBJECTIVE: To investigate apparent aqueous solubility and apparent oil-water partition coefficients of three bufadienolides composition. METHOD: A high performance liquid chromatography method was established to determine apparent aqueous solubility of three bufadienolides composition; apparent oil-water partition coefficients of three bufadienolides composition was determined by shaking flask method. RESULT: The solubility of three bufadienolides composition reached the top value, 76.29 microg x mL(-1) (RBG), 51.85 microg x mL(-1) (CBG), 32.76 microg x mL(-1) (BL) respectively and a total of 160.9 microg x mL(-1) in the condition of 37 degrees C and pH 7.0, therefore three bufadienolides composition can be defined as insoluble products. The solubility of the three decreased in weak acid or base environment to some extent. RBG, CBG, BL are liposoluble components and the sequence of log P is RBG > BL > CBG. CONCLUSION: RBG, CBG, BL is water-insoluble and hydrophobic. Surfactants can be applied to increase the solubility of three bufadienolides composition.

[Diuron degradation process and change of toxicity by gamma-irradiation].

The radiation-induced degradation process of diuron and change of toxicity by gamma-irradiation were investigated. The contribution to diuron degradation by the radicals is in the order of: *OH > e(aq)(-) > *H. The quantum efficiency ratios of *OH, e(aq)(-) and *H for the degradation of diuron are calculated as 3 : 1 : 2. e(aq)(-) and *H could reduce diuron and its degradation product by loss of the chlorine atoms and the addition reaction. Both the shift and alkaline substitute mutations firstly increase and then decrease with the increase of irradiation time. But, the sample only shows mutagenic potential in Ames assay (TA100 strain) when 22.2 min is selected as the irradiation time. The acute toxicity firstly decreases and then increases with the increase of irradiation time and the more toxic substances are produced.

[Sorption and desorption behaviors of tetrabromobisphenol A on fluvo-aquic soil].

Sorption and desorption behaviors of tetrabromobisphenol A (TBBPA) on fluvo-aquic soil were investigated using batch equilibrium experiments, and the effects of pH and ionic strength on the sorption were also evaluated. The results showed that the sorption process could be divided into the rapid sorption (0-24 h) and the slow sorption (24-48 h). The rapid sorption played the main role in the sorption of TBBPA and the sorption approached equilibrium at about 48 h. The nonlinear isotherm of TBBPA on the soil was observed, and the sorption behavior could be described by Freundlich model well. The amount of TBBPA sorption decreased with the increase in solution pH within the range of pH 6.0-8.0, and did not change significantly with the increase in solution pH when pH value was greater than 8.0. The amount of TBBPA sorption increased with the increase in ionic strength. In addition, the result of sorption-desorption revealed that desorption hysteresis of TBBPA, which suggested that the fluvo-aquic soil had high affinity with TBBPA.

[Studies on preparation of sinomenine hydrochloride-loaded bovine serum albumin microspheres].

OBJECTIVE: To prepare Sinomenine hydrochloride-loaded bovine serum albumin microspheres (SM-BSA-MS). METHOD: SM-BSA-MS was prepared by spray drying technique. The morphology, drug-loading and release in vitro of SM-BSA-MS was studied. RESULT: The diameters of SM-BSA-MS were in the range of 1-3 m. The drug loading of microspheres, formulated with different drug/albumin ratios as 1, 2, 1:1, 2:1, were 31.6%, 47.7% and 67.9% , respectively. And the drug entrapment efficiencies of different drug/albumin ratios were higher than 94%. The results of in vitro release experiments showed that the drug loaded microspheres have the properties of sustained-release compared with the Sinomenine hydrochloride injection. Different release characteristics could be obtained by adjusting the prescription composition and the thermal denaturation condition. CONCLUSION: Spray drying technique is a simple and feasible method for preparing SM-BSA-MS. The drug loaded microspheres had high drug-loading and sustained-release effect.

[Optimization preparation of chansu-loaded solid lipid nanoparticles by central composite design and response surface method].

OBJECTIVE: To optimize the formulation of chansu-loaded solid lipid nanoparticles (Cs-SLN). METHOD: Cs-SLN was prepared by cold homogenization technique. The effects of influence factors such as the weight of compritol 888 ATO, soybean lecithin and poloxamer 188, on mean diameter, entrapment efficiency, drug loading and overall desirability were investigated by using central composite design and response surface method. The data were imitated using multi-linear equation and second-order polynomial equation. RESULT: The latter was prior to the former considering from multiple correlation coefficients. Under the optimal conditions, the mean diameter, entrapment efficiency, drug loading of the Cs-SLN were 71.5 nm, 92.45% and 5.26%. CONCLUSION: The optimized preparation technique for Cs-SLN is stable, feasible and high inclusion rate. It can be used for production of Cs-SLN.

[Freeze-drying of silymarin-loaded solid lipid nanoparticles (SM-SLN)].

OBJECTIVE: To investigate lyophilization of SM-SLN. METHOD: The parameters of lyophilization process was optimized. In addition, the protective effect of various types and concentrations of cryoprotectants were tested by shape, colour and disparity. RESULT: The mixture of 2% lactose and 2% glucose could better prevent nanoparticles from aggregating, the optimal lyophilization process was followed: precooled at -45 degrees C for 10 hr; primary drying at -25 degrees C for 5 hr; secondary drying at 10 degrees C for 3 hr; finally drying at 30 degrees C for 6 hr. CONCLUSION: Changes in particle size distribution during lyophilization could be minimized by optimizing the parameters of the lyophilization process and adding supporting agent.

[Effect of particle size on oral absorption of silymarin-loaded solid lipid nanoparticles].

OBJECTIVE: To investigate effect of particle size on oral absorption of silymarin-loaded solid lipid nanoparuicles. METHOD: Solid lipid nanoparticles (SLN) of various sizes (150 nm, 500 nm and 1000 nm) using Compritol 888 ATO as the material and silymarin (SM) as a model drug were prepared. Silybinin concentration in plasma of rats were determined by RP-HPLC with UV detector. The main pharmacokinetic parameters were calculated by 3p97. RESULT: Results showed that the AUC of 150 nm SLN was 2.08 fold that of 500 nm SLN and 2.54 fold of 1000 nm SLN treated orally to rats (P < 0.05). The oral bioavailability of 150 nm SLN was remarkably higher than the other two size SLN. CONCLUSION: This has important implications in designing of SM-SLN as a new oral drug delivery system.

[Human recombinant interferon-alpha 2a polybutylcyanoacrylate sustained release lyophilized nanospheres for liver-targeting].

OBJECTIVE: To evaluate the liver-targeted and sustained release characteristics of human recombinant interferan-alpha 2a polybutylcyanoacrylate lyophilized nanospheres (rIFN alpha 2a-PBCA-NS). METHODS: Emulsification/polymerization method was used to prepare the nanospheres which was lyophilized to obtain rIFN alpha 2a-PBCA-NS, and cell pathological embarrassment (CPE) was used to determine the rIFN alpha 2a concentration in the preparations and biological samples. The in vivo distribution and pharmacokinetics in liver after intravenous injection (i.v.) of rIFN alpha 2a-PBCA-NS and rIFN alpha 2a in mice were evaluated. RESULTS: The rate of entrapment of the nanospheres was (56.2 +/- 4.3)%; the particle diameter, span of rIFN alpha 2a-PBCA-NS were (108 +/- 37) nm and 0.55, respectively, and their biological activity had little change after being stored at 3-5 degrees C for 6 months. The distribution ratio of rIFN alpha 2a after i.v. in mice liver increased from 13.1% (for rIFN alpha 2a) to 50.6% (for rIFN alpha 2a-PBCA-NS), and the mean retain time from 1.41 h (for rIFN alpha 2a) to 8.35 h (for rIFN alpha 2a-PBCA-NS). Of the distribution parameters (te for rIFN alpha 2a, re and te for rIFN alpha 2a-PBCA-NS) in 5 main organs, the largest ones were in liver and both re and te for rIFN alpha 2a-PBCA-NS in liver larger than one. CONCLUSION: The rIFN alpha 2a-PBCA-NS showed obviously liver-targeting and sustained release characteristics.