Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn²⁺), and arsenate (AsO₄ ^3-) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an "all-in-one" theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer. In present study, nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2 (MMP-2) dual-responsive, tumor targeting, and size-variability were designed for enhancing the antitumor efficacy and achieving "on-demand" drug release markedly. Based on the thermal sensitivity of gelatin, we designed a size-variable gelatin nanoparticle (GNP) to encapsulate indocyanine green (ICG) and doxorubicin (DOX). Under an 808 nm laser irradiation, GNP-DOX/ICG responded photothermally and swelled in size from 71.58 ± 4.28 to 160.80 ± 9.51 nm, which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics. Additionally, GNP-DOX/ICG showed a size reduction of the particles to 33.24 ± 4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor. In the subsequently performed

Objective Fluctuation of glucose levels is more likely to cause oxidative stress which contributes to the development of insulin resistance through activating c-Jun N-terminal kinase (JNK).Such antio xidants as vitamin C or vitamin E do not appear very helpful.Radix Astragali (RA) is an herbal medicine with antioxidative ability.The study was to explore whether RA would lower the risk of insulin resistance in diabetic rats.Methods Diabetic rats received RA,insulin or both RA and insulin after diabetes were induced in male Wistar rats.Serum levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNFα),advanced glycation endproducts(AGEs) levels in kidney,the expression of insulin receptor (IR),insulin receptor substrate 1 (IRS-1),p38 mitogen-activated protein kinase (MAPK),p-p38 MAPK,p-JNK,p-IRS-1 Ser307,and p-IRS-1 Tyr612 in skeletal muscles were determined.Results Compared to diabetic rats treated with insulin,the diabetic rats treated with both insulin and RA demonstrated significantly lower levels of IL-6,TNF-α and AGEs (P ＜ 0.05),significantly lower activation of p-p38 MAPK and JNK (P ＜0.05),significantly higher expressions of IRS-1 (P ＜0.05),p-IRS-1 Tyr612,and significantly lower expression of p-IRS-1 Ser307 (P ＜ 0.05).Conclusions RA can lower the risk of insulin resistance through fighting oxidative stress in diabetic rats.

Objective To investigate the current situation of pharmaceutial research and influencing factors in primary hospitals located in Hangzhou Fuyang county.Methods A designed questionnaire was used collecting information from the pharmacists of six Fuyang city medical institutes.Results Among 156 valid questionnaires 54 (34.62％) pharmacists showed their interest in pharmaceutial research,however only 4 of them had the opportunity to participate or host such project.The top reason of interesting in research was that it would help in their job promotion and enhance their own value.We found that most of pharmacists thought that it is very difficulties to conduct research and it is not necessary to do so.The educational background was found to related with research interest with a statistical significance (P＜0.001);and the difference in accomplishment was statistically significant among pharmacists (P＜0.05).Conclusions Current status of research in primary hospital pharmacists is worrysome.The hospital administrators need to pay great attention to medical research,make efforts to develop and provide the excellent policy and technological platform to enhance the research activities of pharmacists.

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.

[Objective] To prepare adriamycin self-assembled nanoparticles, and study the in vivo anti-tumor activity. [Methods]The self-assembled adri-amycin loaded cholesterol-modified pul ulan nanoparticles were prepared by dialysis and were characterized by morphology for particle size,Zeta potential, entrapment efficiency,drug loading content.They were incubated with U251 cel s to assess the inhibition ability of the self-assembled adriamycin-loaded cholesterol-modified pul ulan nanoparticles. [Results]The morphology of self-assembled adriamycin loaded cholesterol-modified pul ulan nanoparticles was spherical. The mean particle size, Zeta potential, entrapment efficiency and drug loading were (112.8 ±1.02)nm,(-27.2±0.246)mV,(67.14±1.21)% and (7.65±0.58)%, respectively.The profiles of release were expressed wel by Higuchi equation. When the dosages were 25μg·mL-1 plus, the inhibiton ability against U251 was stronger than adriamycin solution( P<0.01).[Conclusion]The self-assembled adriamycin loaded cholesterol-modified pul ulan nanoparticles exhibited more cycitoxic activity against U251 than adriamycin solution.

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 (P < 0.01), causing obvious reductions of cell survival rate, with no significant difference between them (P > 0.05). 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 (P < 0.01), and the permeability of P-80-NT-NP was greater than that of NT-NP (P < 0.05). 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.

OBJECTIVETo investigate the absorption enhancen effect of borneol/mentholum eutectic mixture (BO/ME) on nasal-brain delivery of neurotoxin loaded nanoparticles.

METHODUsing microdialysis sampling technique in awake freely-moving rats, the counter per minute (cpm) of dialysates in right PAG of NT-loaded nanoparticles with the BO/ME (BO/ME-NT-NP), radiolabeled with sodium 125I-Iodide, were measured in a gamma-counter for radioactivity. After converting cpm into corresponding concentrations of NT byin vivorecovery of microdialysis probes, the pharmacokinetic parameters were calculated.

RESULTThe BO/ME-NT-NP could be absorbed into the brain, much better to NT-NP and the nanoparticles with borneol or menthdlum only, and the pharmacokinetics accorded with the two-compartment model. The parameters tmax, cmax, AUC, t 1/2(beta) were 0.68 h, 27.32 ng x mL(-1), 132.68 ng x h x mL(-1), 3.1076 h.

CONCLUSIONWith adding BO/ME as absorption enhancer, NT could be significantly increased in the brain with the help of nanopartilces as carriers, and the time to maximal concentration was short, the elimination process was prolonged.

Absorption ; drug effects ; Animals ; Bornanes ; chemistry ; pharmacology ; Brain ; metabolism ; Drug Carriers ; pharmacokinetics ; Male ; Menthol ; chemistry ; pharmacology ; Microdialysis ; Nanoparticles ; Nasal Cavity ; metabolism ; Neurotoxins ; administration & dosage ; pharmacokinetics ; Rats

[Objective] To investigate the possibility of [poly(lactic-co-glycolic acid) ,PLGA] nanoparticles (NP) as a new kind of protein drug carrier for nasal administration. [Method] CNT-PLGA-NP was prepared by double emulsification solvent evaporation. Its morphology was examined by transmission electronmicroscope (TEM). In the use of photon correlation spectroscopy(PCS) and laser Doppler anemometry(LDA),its Zeta potential and mean particle size were estimated .Also, the entrapment efficiency of CNT-PLGA-NP and its pharmacokinetics in rats through nasal administration were studied. [Result] The Zeta potential, mean particle size, entrapment efficiency of CNT-PLGA-NP were-13.4mV, 320.20nm and 45% respectively .Its vitro CNT release from CNT-PLGA-NP appeared to consisting of two components with initial rapid release followed by a exponential stage.The AUC and t1/2(?) of CNT, CNT-PLGA-Np and CNT-PLGA-NP(B+T)were 1.14, 8.37, 7.12?g?h/mL and 20.06, 44.14, 34.82h respectively. [Conclusion]PLGA-NP might be a potential new drug carrier for CNT.Polysorbate 80 and borneol might be good absorption enhancers.