Search

Our previous work indicates the lymphatic network and perivascular spaces or tissues might be involved in the facial intradermal brain-targeted delivery of Evans blue (EB). In this article, we presented the detailed involvement of both, and the linkage between lymphatic network and perivascular spaces or tissues. The in-vivo imaging, the trigeminal transection and immunohistochemistry were used. In-vivo imaging indicated intradermal injection in the mystacial pad (i.d.) delivered EB into the brain at 2-, 6- and 24 h, while intranasal injection (i.n.) delivered EB into the rostral head and intravenous injection (i.v.) diffused EB weakly into the brain. Trigeminal perineurial and epineurial EB occurred along the perivascular spaces or tissues and along brain vessels. EB diffused into the lymphatic vessels and submandibular lymph nodes. Moreover, perineurial and epineurial EB co-located or overlaid with Lyve1 immuno-reactivity and VEGF antibody, and lymphatic network connected with perivascular spaces or tissues, suggesting lymphatic system-perivascular spaces might involve in the EB delivery with i.d. The trigeminal transection reduced the trigeminal epineurial and perineurial EB and brain EB along vessels. EB diffused in the fasciculus and the perineurium, blood and lymphatic vessels in the mystacial pad, mystacial EB overlaid VEGF or Lyve1 antibody. In summary, the dermal-trigeminal-brain perivascular spaces or tissues and the linkage to the lymphatic network mediated the intradermal brain-targeted delivery.

The quality characteristics of ‘Xiangshui’ pears (Pyrus ussuriensis) treated with different concentrations of biomass pyrolysis liquid (BPL) during storage at 25℃ were investigated. The weight of ‘Xiangshui’ pears treated with BPL declined at a slower rate than that of the control. The rot index of BPL-treated ‘Xiangshui’ pears decreased with increasing storage times, and treatment with 20-fold-diluted BPL resulted in the lowest rot index after storage for 12 days. The total acid content of ‘Xiangshui’ pears treated with 20-fold-diluted BPL was 0.19%, and was the highest after storage for 12 days. After storage for 12 days, the total sugar content of ‘Xiangshui’ pears treated with 20-fold-diluted BPL was 7.19%; this was significantly higher than that of the control, but not significantly different from that of pears treated with other BPL dilutions. The vitamin C content of ‘Xiangshui’ pears showed a decreased trend, and pears treated with 20-fold-diluted BPL had a vitamin C content of 2.21 mg/100 g after storage for 12 days and showed the least decline compared to other treatments. In addition, respiration in ‘Xiangshui’ pears was effectively inhibited by treatment with BPL. In conclusion, BPL treatment exerts a protective effect on the quality of ‘Xiangshui’ pears during storage, with 20-fold-diluted BPL being the most effective.

In order to prepare angiopep-2 modified fluorescein isothiocyanate-labeled neurotoxin nanoparticles( ANG-NPs/FITCNT),emulsion/solvent evaporation method was used with m PEG-PLA and ANG-PEG-PLA( in proper proportions) as carriers and with FITC-NT as drug. With particle size and encapsulation efficiency as comprehensive indexes,the effects of different ultrasound power and ultrasound time combinations on the process were investigated. The in vitro release characteristics of nanoparticles in PBS buffer at p H 7. 4 and p H 6. 5 were investigated by dialysis method. The results indicated that the optimum process for preparing ANG-NPs/FITC-NT was as follows: ultrasonic power 90 W,ultrasonic time 30 s. In such optimal process,ANG-NPs/FITC-NT were well-shaped under the transmission electron microscope,with an average particle size of( 123. 9±0. 5) nm,Zeta potential of(-10. 5±0. 5) m V,encapsulation efficiency of( 68. 1±0. 4) %,and the drug loading of( 0. 82±0. 01) %. The in vitro drug release profiles of the nanoparticles in PBS buffer at p H 7. 4 and p H 6. 5 were both consistent with Ritger-Peppas equation,ln Q = 0. 508 8 lnt-2. 285 0,r = 0. 961 5( p H 7. 4) and ln Q= 0. 449 9 lnt-1. 855 3,r = 0. 970 3( p H 6. 5),respectively. The experiment results proved that the nanoparticles prepared by emulsion/solvent evaporation method had uniform particle size,high encapsulation efficiency and in vitro sustained release characteristic,which might be a potential carrier for NT intracerebral drug delivery.

This study was to investigate the influence of spray drying conditions on the physicochemical characteristics and sensory evaluation of mandarin (Citrus unshiu) beverage powder. The results show that moisture content, color, pH, vitamin C, water solubility index and drying yield were significantly affected by the carrier agent concentrations and the inlet air temperatures. However, water activity and water absorption index were not significantly influenced by the spray drying conditions. Sensory evaluation results of taste, color and overall acceptability of mandarin beverage powders added with corn syrup were higher than those added with maltodextrin. As the result of process suitability for spray drying mandarin beverage by using different parameters, it is concluded that 35% corn syrup concentration and 135 °C inlet temperature were suitable to produce mandarin beverage powder with preferable taste and color.

Biomass is a renewable energy resource derived from all organic materials produced by both human and natural activities. Total biomass is amounted to be 58,010 Gg yr−1 from agricultural sector during 2013 in Korea: livestock manure, crop residues, and agro-industrial wastes. Potential methane production from agricultural biomass was calculated based on IPCC guidelines using manipulated equations. The main parameters were emission factor, total waste amount, and physico-chemical properties of each waste to estimate methane production. Calculated total potential methane production from the different categories for livestock, crop residues, and agro-industrial wastes was 502 Gg yr−1 in Korea. Poultry waste generated the highest methane potential with 227 Gg yr−1 followed by 80 Gg yr−1 from cattle waste. For crop residues and agro-industrial wastes, estimated methane production was 1 and 126 Gg yr−1, respectively. Results of this study show that livestock manure gave the highest methane emission in the agricultural sector. With this, more effective management of livestock wastes is necessary to develop and maximize technology on harnessing methane as alternative energy.

In order to optimize the prescription and preparation process of norcantharidin/tetrandrine dual loaded liposomes, the dual drug loaded liposomes were prepared by film dispersion-ultrasonic method using norcantharidin-mesoporous silica nanoparticles（MSN-NCTD）and tetrandrine（Tet）. With particle size and encapsulation efficiency as comprehensive indexes, the influences of phospholipid cholesterol amount, ultrasonic time and ultrasonic power on prescription process were investigated by orthogonal test; the

Arsenic trioxide (ATO) is an effective component of traditional Chinese medicine arsenic. The existing studies have shown its good inhibition and apoptosis ability on a variety of tumours. However, its toxicity and difficulties in the permeability into the blood brain barrier (BBB) has the limitation in the application of glioma treatment. Polyamide-amine dendrimer (PAMAM) is a synthetic polymer with many advantages, such as a good permeability, stability and biocompatibility. Additionally, the 5th generation of PAMAM is an ideal drug carrier due to its three-dimensional structure. In this study, the 5th generation of PAMAM co-modified with RGDyC and PEG, then confirmed by ¹H-NMR. The average particle size of nanoparticles was about 20 nm according to the nanoparticle size-potential analyser and transmission electron microscopy.

Fermented soybean foods contain nutritional components including easily digestible peptides, cholesterol-free oils, minerals, and vitamins. Various fermented soybean foods have been developed and are consumed as flavoring condiments in Asian regions. While the quality of fermented soybean foods is largely affected by microorganisms that participate in the fermentation process, our knowledge about the microorganisms in soybean pastes manufactured in Northeast China is limited. The current study used a culture-independent barcoded pyrosequencing method targeting hypervariable V1/V2 regions of the 16S rRNA gene to evaluate Korean doenjang and soybean pastes prepared by the Hun Chinese (SPHC) and Korean minority (SPKM) populations in Northeast China. In total, 63399 high-quality sequences were derived from 16 soybean paste samples collected in Northeast China. Each bacterial species-level taxon of SPHC, SPKM, and Korean doenjang was clustered separately. Each paste contained representative bacterial species that could be distinguished from each other: Bacillus subtilis in SPKM, Tetragenococcus halophilus in SPHC, and Enterococcus durans in Korean doenjang. This is the 1st massive sequencing-based study analyzing microbial communities in soybean pastes manufactured in Northeast China, compared to Korean doenjang. Our results clearly showed that each soybean paste contained unique microbial communities that varied depending on the manufacturing process and location.

A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.

Aim: To investigate the effects of renal ischemic preconditioning (IPC) on both renal hemodynamics and the renal interstitial concentrations of adenosine and adenine nucleotides induced by ischemia-reperfusion injury. Methods: Renal hemodynamics responses to ischemia-reperfusion injury in mongrel dog models were determined with or without multiple brief renal ischemic preconditioning treatments, as well as the adenosine A1 receptor antagonist (KW-3902), respectively. The renal interstitial concentrations of adenosine and adenine nucleotides in response to ischemia-reperfusion injury, either following 1–3 cycles of IPC or not, were measured simultaneously using microdialysis sampling technology. Results: One 10-min IPC, adenosine A1 receptor antagonist (KW-3902) also shortened the recovery time of renal blood flow (RBF) and urine flow (UF), as well as mean blood pressure (BP). Advanced renal IPC attenuated the increment of adenosine and adenine nucleotides, as well as recovery time during the 60-min reperfusion which followed the 60-min renal ischemia. All of these recovery times were dependent on the cycles of 10-min IPC. The renal interstitial concentrations of adenosine and adenine nucleotides increased and decreased during renal ischemia and reperfusion, respectively. Conclusion: A significant relativity in dog models exists between the cycles of 10-min renal IPC and the recovery time of BP, UF, and RBF during the 60-min renal reperfusion following 60-min renal ischemia, respectively. Renal IPC can protect against ischemia-reperfusion injury and the predominant effect of endogenous adenosine induced by prolonged renal ischemia; renal adenosine A1 receptor activation during the renal ischemia-reperfusion injury is detrimental to renal function.

Curcumin has a wide spectrum of pharmaceutical properties such as antitumor, antioxidant, antiamyloid, and anti-inflammatory activity. However, poor aqueous solubility and low bioavailability of curcumin are major challenge in its development as a useful drug. To overcome many of these problems, curcumin-loaded long-circulating liposomes (Cur-LCL) were prepared by the ethanol injection method. Morphology of Cur-LCL was observed by transmission electron microscope, mean particle size and Zeta potential were detected by laser particle size analyzer, entrapment efficiency and drug loading were evaluated by ultracentrifugation. The drug release behavior in vitro and pharmacokinetic behavior in rats of Cur-LCL were investigated with curcumin (Cur) and curcumin liposomes (Cur-Lips) as control. The results showed that the mean diameter of Cur-LCL was 110 nm, the Zeta potential was -5.8 mV. The entrapment efficiency and drug loading of Cur-LCL was 80.25%, 2.06%, respectively. The release behavior in vitro studied by dialysis in PBS buffer showed significant sustained release profile that 48.95% Cur were released from Cur-LCL in 7 h, 88.92% in 24 h. The pharmacokinetic parameters showed that compared with Cur and Cur-Lips, the t(1/2beta) of Cur-LCL was extended to 13 and 1.8-fold, respectively. Besides, the AUC values was significantly increased (P0.01), and the clearance was evidently decreased (P0.01). These results from in vitro and in vivo indicated that Cur-LCL were able to realize controlled drug release and increase circulation time.

The purpose of this study was to investigate the absorption kinetics of aconitine, mesaconitine and hypaconitine in rats after oral administration of Sini Tang powder. With cannulate portal and jugular veins cannulated (double-cannulate), conscious moving rats were orally administered Sini Tang. Then samples of portal and systemic blood were collected at the designated periods of time and analyzed for aconitine, mesaconitine and hypaconitine by HPLC. Apparent absorption coefficient of aconitine, mesaconitine and hypaconitine was caculated respectively. The results indicated that the apparent absorption coefficient of aconitine, mesaconitine and hypaconitine come from Sini Tang were 0. 336, 0. 090, 0. 176, respectively, which had some differences among them. It was also suggested that double-cannulated rat was useful for estimating the absorption kinetics of aconitine, mesaconitine and hypaconitine after orally administered Sini Tang by determining the AUC values for drugs in portal and systemic blood samples. The three alkaloids could all be detected in blood, but the absorption differences were existed among the three alkaloids.

OBJECTIVE To prepare chitosan-modified tripterygium glycoside nanoparticles (LMWC-TG-PLA-NPs), and assess its renal targeting property in rats. METHOD Chitosan-modified tripterygium glycoside nanoparticles (LMWC-TG-PLA-NPs) were prepared by modified spontaneous emulsification solvent evaporation method, and modified with 50% deacetylated low molecular weight chitosan (LMWC). The shape of nanoparticles was observed under a transmission electron microscope. The mean diameter of nanoparticles was measured by particle size analyzer. The drug encapsulation efficiency and drug loading were measured by centrifuge method. The in vitro release behavior was studied with dialysis bags. Renal microdialysis technique and renal artery administration technique were combined to study the renal targeting property of nanopartcles. LMWC-TG-PLA-NPs were administrated in rats by tail vein injection (TVI) and renal artery administration (RAA), respectively, with TG-PLA-NPs as the control group. Renal dialysis fluid was regularly collected to determine the drug concentration in the dialysis fluid, map drug concentration-time curves, and calculate AUC ratio in kidneys through the two injection approaches as the renal targeting parameter (RTP), in order to assess the renal targeting property of LMWC-TG-PLA-NPs. RESULTS The prepared LMWC-TG-PLA-NPs looked smooth and round. Their average diameter, polydispersity index, encapsulation efficiency and drug loading were (207.6 +/- 3.4) nm, (0.078 +/- 0.009)%, (61.83 +/- 2.43)%, and (10.70 +/- 0.37)%, respectively. The pH 7.4 PBS buffer solution containing 20% ethanol showed obvious sustained release behavior. LMWC-TG-PLA-NPs showed a RTP of 71.97%, which was 3.6 times of TG-PLA-NPs of the control group. CONCLUSION The prepared LMWC-TG-PLA-NPs showed high drug encapsulation efficiency and drug loading, with obvious sustained release characteristics and renal targeting property. LMWC-TG-PLA-NPs are expected to become a new type vector for reducing toxic and side effects of tripterygium glycoside. Meanwhile, a new method is established for assessing renal targeting property with AUC ratio in kidneys after administrated through caudal veins and renal arteries as the renal targeting parameter.

The mesaconitine and its major metabolites in the rat urine were identified by liquid chromatography and electrospray ionization tandem mass spectrometry. The rat urine was collected for consecutive 24 hours from the rat following intragastric infusion of mesaconitine, subsequently which were enriched and purified using solid phase extraction. The metabolites of mesaconitine in the rat urine were analyzed by the liquid chromatography and electrospray ionization tandem mass spectrometry. It is shown that the parent drug mesaconitine and its metabolites were found in the rat urine, such as hypo-mesaconitine glucuronic acid conjugate, 10-hydroxy-mesaconitine, 1-O-demethyl mesaconitine, deoxy-mesaconitine and hypo-mesaconitine. Among the five of metabolites, the hypo-mesaconitine glucuronic acid conjugate (m/z 766) was first discovered as the aconitine in rats phase II metabolites, which revealed a new way of mesaconitine metabolism in rats.

This study was aimed at the transport across blood-brain barrier (BBB) of polysorbate-80 modified neurotoxin loaded polybutylcyanoacrylate nanoparticle (P-80-NT-NP) and its cytotoxicity. An in vitro model of BBB using rat brain microvascular endothelial cells (rBMECs) was established. The cytotoxicity of P-80-NT-NP was measured by the MTT assays, where neurotoxin (NT), nanoparticle (NP), neurotoxin nanoparticle (NT-NP) as control, and the permeability of P-80-NT-NP was determined by using of Millicell insert coculture with rBMECs and fluorescence spectrophotometry. MTT results showed that NT, NP, NT-NP and P-80-NT-NP were avirulent to rBMECs when the concentration of NT was lower than 200 ng x mL(-1). But the cytotoxicity of NP, NT-NP and P-80-NT-NP would be augmented accordingly as concentration increased (P0.01), causing obvious reductions of cell survival rate, with no significant difference between them (P0.05). When the concentration of NT was 150 ng x mL(-1), the permeability on rBMECs of P-80-NT-NP and NT-NP were both significantly higher than that of NT (P0.01), and the permeability of P-80-NT-NP was greater than that of NT-NP (P0.05). In conclusion, polysorbate-80 modified neurotoxin nanoparticles can transport across the BBB, while concentration of NT is greater than 200 ng x mL(-1), P-80-NT-NP has a little cytotoxicity against rBMECs.

The purpose of this paper is to encapsulate neurotoxin-I (NT-I), a kind of analgesic peptide, into polylactic acid (PLA) nanoparticles (NPs) and to evaluate their transport into the brain after intranasal administration (in) by use of microdialysis sampling technique developed in our laboratory recently. NT-I-NPs (NT-Iradiolabeled with sodium 125I-Iodide) were prepared by a double emulsification solvent evaporation method, and were characterized in terms of surface morphology, particle size distribution, zeta potential and entrapment efficiency. Then, NT-I-NPs were administered intranasally or intravenously to rats and the radioactivities in periaqueductal gray (PAG) were monitored up to 240 min utilizing the microdialysis sampling technique. Nanoparticles prepared were spherical with homogenous size distribution. Their mean particle size and zeta potential measured were (65.3 +/- 10.8) nm and (-28.6 +/- 2.3) mV, respectively. The entrapment efficiency of NT-Iencapsulated into nanoparticles was (35.5 +/- 2.8)%. The brain transport results showed that the time to peak level (Tmax) of NT-I-NPs (in) was (65 +/- 10) min approximately, apparently shorter compared with NT-I-NPs [iv, (95 +/- 10) min] or NT-I [iv, (145 +/- 10) min]. The concentration to peak level (Cmax) and the area under the curves from zero to 4 h (AUC0-4h) of each group followed this order: NT-I-NPs (in)NT-I-NPs (iv)NT-I (iv). With nanoparticles as carriers and administered intranasally could be a potential way for centrally active peptides to improve their brain transport. Microdialysis is quite a good technique for the study of drug delivery to the brain.

Intracerebral microdialysis (IC-MD) has been developed as a well-validated and powerful technique for decades. As a practical sampling tool, it can gain the continuous dialysates of endogenous and exogenous substances in extracellular fluid (ECF) of awake freely moving animals. Also, variform IC-MD probes (IC-MDPs) have grown more exquisite. The implantation of the IC-MDP in certain tissue of brain allows monitor drug distribution and measure drug and corresponding neurotransmitters levels in brain ECF after administration for brain pharmacokinetic-pharmacodynamic (B-PK-PD) study. So it is suitable for IC-MD to B-PK-PD study (IC-MD/B-PK-PD). The performance of IC-MD/B-PK-PD can not only elevate the degree of precision and accuracy of experimental data, minimize the individual difference by reduced number of animals, but also give important information for the prediction and optimization of drug effective dose in preclinical study. In this review, we have discussed various IC-MD/B-PK-PD studies of analgesic, antiepileptic and antidepressant drug. The role of IC-MD/B-PK-PD in confirming and assessing the drug effect before clinic trials is highlighted.

To investigate the effects of renal ischemic preconditioning (IPC) on both renal hemodynamics and the renal interstitial concentrations of adenosine and adenine nucleotides induced by ischemia-reperfusion injury.Renal hemodynamics responses to ischemia-reperfusion injury in mongrel dog models were determined with or without multiple brief renal ischemic preconditioning treatments, as well as the adenosine A1 receptor antagonist (KW-3902), respectively. The renal interstitial concentrations of adenosine and adenine nucleotides in response to ischemia-reperfusion injury, either following 1-3 cycles of IPC or not, were measured simultaneously using microdialysis sampling technology.One 10-min IPC, adenosine A1 receptor antagonist (KW-3902) also shortened the recovery time of renal blood flow (RBF) and urine flow (UF), as well as mean blood pressure (BP). Advanced renal IPC attenuated the increment of adenosine and adenine nucleotides, as well as recovery time during the 60-min reperfusion which followed the 60-min renal ischemia. All of these recovery times were dependent on the cycles of 10-min IPC. The renal interstitial concentrations of adenosine and adenine nucleotides increased and decreased during renal ischemia and reperfusion, respectively.A significant relativity in dog models exists between the cycles of 10-min renal IPC and the recovery time of BP, UF, and RBF during the 60-min renal reperfusion following 60-min renal ischemia, respectively. Renal IPC can protect against ischemia-reperfusion injury and the predominant effect of endogenous adenosine induced by prolonged renal ischemia; renal adenosine A1 receptor activation during the renal ischemia-reperfusion injury is detrimental to renal function.

The aim of the present study was to determine the effects of benidipine on renal function and whether benidipine may dilate the efferent arteriole as well as the afferent arteriole of the canine kidney. The effects of benidipine on the renal segmental vascular resistance were estimated using Gomez's formula with some modification. The renal hemodynamic action of benidipine was also compared with that of amlodipine. Intrarenal arterial injection of benidipine at a dose of 3 microg/kg resulted in a significant increase in renal blood flow (RBF), urine flow and urinary excretion of sodium, but not in glomerular filtration rate (GFR). Amlodipine at a dose of 300 microg/kg also increased RBF, urine flow and urinary excretion of sodium to a significant degree equivalent to that by benidipine. However, in contrast to benidipine, amlodipine significantly increased GFR. After the administration of benidipine, autoregulation of RBF and GFR was relatively maintained and the renal perfusion pressure (RPP)-RBF relation shifted upward; that is, RBFs at 75 and 50 mmHg were maintained at a higher level than those of the control. In contrast to benidipine, amlodipine diminished the autoregulation of RBF and GFR. RBFs at 75 and 50 mmHg were not different from those of the control. The afferent and efferent arteriolar resistance (Ra and Re) were calculated based on the RPP-RBF and RPP-GFR relations. Benidipine reduced both Ra and Re, but amlodipine selectively reduced Ra. Benidipine increased RBF but not GFR via the dilation of both afferent and efferent arterioles. Thus, benidipine has unique renal hemodynamic actions which differ from those by most calcium antagonists.

Due to their small particle size and large and modifiable surface, nanoparticles have unique advantages compared with other drug carriers. As a research focus in recent years, polyethylene glycol-polylactic acid (PEG-PLA) block copolymer and its end-group derivative nanoparticles can enhance the drug loading of hydrophobic drugs, reduce the burst effect, avoid being engulfed by phagocytes, increase the circulation time of drugs in blood, and improve bioavailability. Additionally, due to their smaller particle size and modified surface, these nanoparticles can accumulate in inflammation or target locations to enhance drug efficacy and reduce toxicity. Recent advances in PEG-PLA block copolymer nanoparticles, including the synthesis of PEG-PLA and the preparation of PEG-PLA nanoparticles, were introduced in this study, in particular the drug release and modifiable characteristics of PEG-PLA nanoparticles and their application in pharmaceutical preparations.