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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
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The purpose of this study was to develop and evaluate a transdermal delivery system for RIS using hydrogels. First, the effects of different concentrations of hydroxypropyl methylcellulose and Carbomer 934 [CBR] on RIS permeation were investigated in porcine skin. The optimized formulation was chosen as the base gel to screen for penetration enhancers. The pharmacokinetics of the optimized RIS formulation was then studied in vitro in rabbits. A formulation with 0.5% CBR showed the highest RIS permeation and was selected as the base gel. RIS permeation was further increased by incorporation of Azone, lauryl alcohol, or menthol, and the enhancing effects of the three were dosedependent. When each enhancer combined with propylene glycol [PG] a synergistic effect was found. A combination of 6% menthol and 6% PG exhibited highest RIS in vitro penetration rate and showed a high efficiency in vivo, with a relative bioavailability of 131.53% compared with intragastric administration. These findings showed that 1% RIS in 0.5% CBR, containing a combination of 6% menthol and 6% PG, can deliver doses of RIS that are therapeutically relevant for treating patients with schizophrenia
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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.
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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.
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[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.
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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 0.05). 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.
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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.
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<p><b>OBJECTIVE</b>To investigate the absorption enhancen effect of borneol/mentholum eutectic mixture (BO/ME) on nasal-brain delivery of neurotoxin loaded nanoparticles.</p><p><b>METHOD</b>Using 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.</p><p><b>RESULT</b>The 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.</p><p><b>CONCLUSION</b>With 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.</p>
Subject(s)
Animals , Male , Rats , Absorption , Camphanes , Chemistry , Pharmacology , Brain , Metabolism , Drug Carriers , Pharmacokinetics , Menthol , Chemistry , Pharmacology , Microdialysis , Nanoparticles , Nasal Cavity , Metabolism , Neurotoxins , PharmacokineticsABSTRACT
[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.
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Objective: To observe the effect of JianLiKeLi(JLKL) on immune function of rat with exercise-induced fatigue and discuss the mechanism of its anti-fatigue.Methods: SPF healthy SD rats were randomly divided into five groups:the control group,the SLJ group,the low dose of JLKL group,middle dose of JLKL group and high dose of JLKL group.The chronic fatigue model was established by exhaustive swimming.Eyeball was removed to collect blood,and the ability of T lymphocyte proliferation,NK cells,IL-1 and IL-6 were tested.Results: Compared with the control group,T cells proliferation in the high and middle dose of JKLL groups increased,the activities of NK cells,IL-1 and IL-6 in the three doses of JLKL groups and the SLJ group were all higher(P
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Objective To prepare the supersaturation self-emulsifying drug delivery system(S-SEDDS) containing silymarin and to evaluate its basic properties.Methods With the time of self-emulsifying,the consequence of color visual examination and particle size as parameters,the optimum formulations of silymarin SSEDDS were screened by solubility test,compatibility tests and pseudo ternary phase diagrams.The silymarin concentration was determined by HPLC.The in vitro dissolution characteristics of silymarin S-SEDDS were investigated with silymarin SEDDS as control.Results The optimum silymarin S-SEDDS was composed of medium chain triglycerides(MCT) 40%,Cremophor RH40(ethoxylated hydrogenatedcastor oil) 48%,Labrasol 12%.The time of self-emulsifying was less than 3 min,the average particle diameter was 49.6 nm,the adding amount of hydroxypropyl methylcellulose(HPMC) was 50 mg/g,and the average content of silymarin was 39.3 mg/g.The in vitro dissolution test of silymarin S-SEDDS showed that the presence of a small amount of cellulosic polymer effectively sustained a metastable supersaturated state by retarding precipitation kinetics.Conclusion The designed formulation of silymarin S-SEDDS is reasonable and provides a strong foundation for further development of new preparations.
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Objective To prepare ligustrazine-chitosan microspheres and to investigate the drug release behavior in vitro. Methods Microspheres were prepared using the spray drying method.The encapsulation efficiency was used to evaluate the influence of different formulation and preparation factors,the formulation was optimized by L9(34) orthogonal design.Results The optimal formulation and preparation factors were as follows: chitosan concentration(0.01 g/mL),ratio of chitosan to ligustrazine(1∶4),inlet temperature(120 ℃),air flow rate(500 L/h).The optimized microspheres had a spherical shape,the loading capacity was(18.60?0.15)%,entrapment efficiency was(93.01?0.76)%,the average diameter was(10.69?0.64) ?m.The drug release profile in vitro could be described by Higuchi equation Q=19.798 t1/2+25.209(r=0.997) at 1-15 h,which showed the prepared microspheres obviously had the sustained release effect.Conclusion The encapsulation efficiency of ligustrazine-chitosan microspheres is higher,the preparation method is simple,and the process is stable.It will provide the basis for realizing the industrialization in Chinese materia medica microspheres.
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AIM:To establish the quality standard for Shengxue Micro Capsules(melanteritum,Cortex Cinnamo-(mi,) Endoconcha Sepiae,Colla Corii asini,Placenta Hominis). METHODS: The melanteritum,Endoconcha sepiae was identified by physic-chemical analysis. Cortex Cinnamomi was identified by TLC.UV was employed for the assay of FeSO_4.GC was used to determine Cinnamaldehyde of Shengxue Micro Capsules. RESULTS: Green vitriol,Endoconcha sepiae could be identified by physico-chemical analysis.Cortex Cinnamomi could be identified by TLC.The linear range of FeSO_4 was within 0～20 mg,r = 0.999 8;The average recovery of assay was(96.7%.) The linear range of cinnamaldehyde was within 0.157 5～0.551 4 ?g,r = 0.999 8;The average(recovery) of assay was 101.52%. CONCLUSION: The method is simple, reproducible.It could be used for(quality) control of Shengxue Micro Capsules.
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Aim To prepare NT-Ⅰ loaded nanoparticles with different diameters modified by Methylated-polyethyleneglycol (Me-PEG) and evaluate their brain pharmacokinetics after administered nasally in rats. Methods NT-Ⅰ-NP was prepared by emulsion/solvent evaporation method and MePEG-PLA was used as the carrier material. Microdialysis technique and fluorospectrophotometry were used to determine NT-Ⅰ concentration after nasal administration in the brain of rats. Results The appearance of all NT-Ⅰ-NP groups was round or similar. The AUC(0-t) of below 100 nm NT-Ⅰ-NP was 1.22 fold as that of 100~200 nm NT-Ⅰ-NP,1.34 fold as that of 200~300 nm and 1.60 fold as that of exceed 300 nm NT-Ⅰ-NP(P