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Objective To study the effect of flumazenil on hypnotic mice induced by diazepam and zolpidem ,and to eval-uate the possibility of flumazenil oral administration .Methods First ,Kunming mice were injected intraperitoneally with nor-mal saline and sodium pentobarbital (S + W) ,diazepam and pentobarbital sodium (D + W) ,zolpidem and pentobarbital sodi-um (Z + W) .The hypnotic effect of diazepam and zolpidem on prolonging the sleep time of pentobarbital sodium would be ver-ified by (D + W) group and (Z + W) group .Then the mice were injected intraperitoneally with flumazenil .The sleep time was used as the evaluation index to evaluate the effect of flumazenil against hypnosis . Finally , the oral administration of flumazenil was observed against hypnosis ,which was evaluated by using sleep time as an index .Results Compared with the control group (S+W) ,the diazepam group (D+W) and the zolpidem group (Z+W) significantly prolonged the sleep time in-duced by pentobarbital sodium (P<0 .001 ,P<0 .05);After Intraperitoneal injection of flumazenil ,compared with the diazepam group (D+W) and the zolpidem group (Z+W) ,the sleep time of the diazepam group [F(ip)+D+W] and the zolpidem group [F(ip)+Z+W] were significantly shorter (P<0 .001 ,P<0 .05);After oral administration of flumazenil ,the sleep time of the diazepam group [F(ig)+ D+ W] and the zolpidem group [F(ig)+ Z+ W] were also significantly shorter (P< 0 .001 ,P<0.05) .Conclusion Flumazenil ,whether intraperitoneal injection or intragastric administration ,could antagonize the hypnotic effect of diazepam and zolpidem .It was proved that oral administration of flumazenil had the same effect compared with intrap-eritoneal injection of flumazenil ,which provided the possibility of preparation of oral administration of flumazenil .
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Objective To prepare an in situ gel system for nasal delivery of menthol and to evaluate the safety of this formulation.Methods Menthol in situ gel was prepared with deacetylatedgellan gum.The nasal mucocilia toxicities of this formulation was evaluated using in situ toad palate model.Guinea pig skin sensitization test and the rabbit skin irritation test were conducted.Skin allergy and irritation reaction were monitored and scored.Results No significant effect on nasal mucosa ciliary movement and the morphology of rat nasal mucosa were observed.The formulation did not induce any dermal irritation in rabbits.Skin allergic reaction was not found in guinea pigs.Conclusion The preparation of menthol in situ nasal gel with low ciliary toxicity was easily achieved.This gel has good physiological flexibility.The further investigation was warranted for this formulation as an intranasal drug delivery system.
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Objective To establish methods for the determination of doxorubicin and elacridar, and prepare PLGA nanoparticles for the co-delivery of doxorubicin and elacridar.Methods Ultraviolet spectrophotometry (UV) and high performance liquid chromatography (HPLC) were used to establish the determination method of doxorubicin and elacridar, respectively;co-delivery nanoparticles system was prepared by nanoprecipitation method, and optimizing the prescription was by adjusting the dosage ratio of the two drugs to investigate the particle size,morphology, encapsulation efficiency (EE), drug loading (DL) and in vitro release.Results The linearity of doxorubicin was better in the rang of 1 to 40 μg/ml, A=0.021C+0.002,r=0.999 5;the linearity of elacridar was better in the rang of 0.5 to 100 μg/ml,A=120 742.462 6C+1 974.570 4,r=1.000 0;the particle size was about 50 nm;transmission electron microscope (TEM) showed that nanoparticles were round in shape and had a good dispersion;EE of doxorubicin and elacridar were 56.58%、51.66%,respectively, DL of doxorubicin and elacridar were 1.48%、1.85%,respectively,the molar ratio of two drugs was about 1∶1;the nanoparticles released slowly in vitro.Conclusion The established methods of doxorubicin and elacridar were convenient and efficient, accurate and repeatable.The Co-delivery nanoparticles system was well dispersionand smaller size, which could be used for further studies.
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Glaucocalyxin A (GLA) is a kind of diterpenoid enantiomers with organic chemical structure of en-15-oxo-16-kaurene.It has various pharmacological activities,such as cardiovascular and endothelium cellular protection,anti-blood coagu-lation,anti-Hepatitis B Virus (HBV),anti-tumor,anti-bacteria,anti-inflammation,hypoxic tolerance,immunomodulation and Ca2+ concentration regulation effect,where as its in vivo safety is quite good.As a folk medicine,it is conventionally used to treat hepatitis,gastritis,mastitis,stomachache and arthralgia.It is also used for ischemic and/or hypoxic cardio-cerebrovas-cular diseases such as coronary heart diseases,stenocardia and chronic cerebral circulation insufficiency in clinic.This review gives a summary of the pharmacological effects,biological mechanism,and toxicity of Glaucocalyxin A.
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Objective To study and optimize the preparation condition of pVAX1‐wapA‐loaded nanoparticles and deter‐mine the transfection efficiency .Methods The related effects of the crucial factors for the formation of nanoparticles:concen‐tration of chitosan and TPP ,pH value ,N/P ratio were studied by single‐factor experiment ,with nanoparticles size and zeta potential as index .Cell transfection test was carried out to indicate that enhancement of cell transfection efficiency of nano‐car‐rier .Results Nanoparticles loaded DNA vaccine were nearly spherical shape with uniform particle size chitosan nanoparticle (CS) ,(219 .2 ± 18 .2) nm ;quaternary ammonium chitosan nanoparticles(CSTM) ,(222 .5 ± 15 .6) nm .Zeta potential of CS and CSTM was (24 .7 ± 3 .5) mV ,(19 .6 ± 1 .2) mV and encapsulation efficiency was 91 .24% ,87 .66% ,respectively .CSTM nano‐particle could enhance cellular uptake of pVAX1‐wapA obviously .Conclusion CSTM nanoparticle was proved to be an efficient DNA vaccine delivery vector .
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Objective To investigate the synergic ratio of sorafenib (SO) and sulforaphane (SF) against the hepatocellu‐lar carcinoma cell line HepG2 in vitro .Methods The synergic effect of SO combined with SF against HepG2 cells was deter‐mined by the CCK8 assay (the synergic effect was determined by combination index (CI) value:CI>1 .1 ,antagonistic;0 .9<CI<1 .1 ,additive;CI<0 .9 ,synergic) .The effectiveness of the synergic effect of the synergic ratio was confirmed by the An‐nexinV‐FITC apoptosis experiment and colony formation assay .Results The CCK‐8 assay showed that SO combined with SF at the molar rate of 1∶1 ,1∶10 and 1∶20 exhibited strong antagonism (CI>1 .1) ,whereas 20∶1 ,5∶1 and 1∶5 ratio resul‐ted in synergistic activity (CI<0 .9) .Furthermore ,10∶1 ratio acted as an additive effective (0 .9<CI<1 .1) .The number of colony formation (14 .66 2 .08) of the group treated with SO combined with SF at 5∶1 synergistic ratio was significantly lower than that of the group treated with after SO combined with SF at 1∶1 antagonistic ratio (31 .33 4 .16) (P<0.01) .The early and late apoptosis rate of HepG2 cells (21 .71 ± 6 .06) of the group treated with SO combined with SF at 5∶1 synergistic ratio was significantly higher than that of the group treated with SO combined with SF at 1∶1 antagonistic ratio(6 .64 ± 0 .311)(P<0.01) .Conclusion SO combined with SF at the molar rate of 5∶1 can synergistically inhibit the growth of hepatocellular car‐cinoma cell line HepG2 in v itro .
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Objective To analyze the current problems on tumor‐targeting nanoparticle drug delivery system .Methods Recent researches of tumor‐targeting nanoparticle drug delivery system were collected ,read and summarized .Results Three research fields on tumor‐targeting nanoparticle drug delivery system were reviewed in this article .Conclusion Not only a deeper understanding of the human physiology and tumor biology ,but changes in strategies and experimental methods are needed to make new achievements on nanoparticle drug delivery system .
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Objective To construct an active targeting drug delivery system‐polymer vesicles(PVs), and examined the cellular uptake. Methods Maleimide‐ polyethylene glycol‐poly(lactic‐co‐glycolic acid)(MAL‐PEG‐PLGA)was used as carrier materials to prepare PVs by self‐assembling. And then PVs was modified by Tf and Tet‐1(Tf/Tet‐1‐PVs). To evaluate its ac‐tive targeting, coumarin‐6 was used as a fluorescent probe to analyze cellular uptake of PVs for both BCEC and Neuro‐2a cells. Results PVs was about 80 nm with rounded shape and had obvious film structure. Tf/Tet‐1‐PVs exhibited a significant role in promoting cellular uptake for both BCEC and Neuro‐2a cells compared with control and single ligand‐modified group. Conclusion PVs modified with dual ligands could promote the cell uptake for both brain capillary cells and nerve cells.
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Objective To prepare and characterize salinomycin sodium‐loaded nano liposomes(SLN) .Methods The nano liposomes were prepared by a thin‐film dispersion method .The formula of SLN was optimized by regulating the cholesterol ratio of the nano liposomes ,using the encapsulation efficacy (EE) of SLN as the primary outcome measure .Results Transmission e‐lectron microscope (TEM) showed that SLN was round and had a good dispersion .Dynamic laser scatter (DLS) showed that SLN was of a desired size of 99 nm ,and zeta potential of -33 .5 mV .EE of SLN was 85 .7% and drug loading of 6 .7% .Ac‐cording to the formulation of nano liposomes ,the concentration of salinomycin sodium in water was greatly improved by 15 folds .Additionally ,the nano liposomes were observed to exhibit sustained release characteristics .Conclusion Salinomycin sodi‐um‐loaded nanoliposomes of a desired size of about 100 nm were obtained ,which were well dispersion ,and high EE and drug loading .Solid pharmaceutics foundation for the activity examination of SLN was provided in this research .
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Objective To investigate the optimal method for synthesizing thiolated doxorubicin .Methods Thiolated doxorubi-cin was synthesized through two different methods .Doxorubicin was reacted with 2-iminothiolane (2-IT) and S-acetylthioglycolic acid N-hydroxysuccinimide ester (SATA),respectively.The synthesized thiolated doxorubicin was further characterized by HPLC and MS -ESI techniques .Several factors including molar ratios as well as reaction time were evaluated .Results The results showed that thiolat-ed doxorubicin could be synthesized via both of the two methods successfully .Thiolated doxorubicin could be stable when doxorubicin was reacted with SATA .But the crude thiolated doxorubicin could be cyclized easily when doxorubicin was reacted with 2-IT.Conclu-sion Thiolated doxorubicin prepared with SATA is more feasible than that with 2-IT.
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Now the layer-by-layer self-assembling (LbL) technique has become an attention-getting reparative methodology for ultrathin film formation. Many scientists in different academic areas including bioengieering, medical science, drug controlled release, optoelectronics dive into this technology. Among of them, carriers with structures which can be flexibly controlled are more useful since functional structure units can be assembled in layer-by-layer fashion, which is simplicity, chemical mildness, concealment, can achieve targeted drug delivery and so on. In this review, we have discussed the advantage, development, influential factors and applications of LbL. We have focused on reviewing the applications and perspective of nanoparticles, microgels and capsules were both fabricated via the LbL assembling at drug delivery.
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BACKGROUND: Bupivacaine is widely used to alleviate post-operation pain and cure acute and chronic pain caused by inflammation or cancer.Its analgesic time cannot meet the request that drug is released slowly to prolong the analgesic time in clinic.OBJECTIVE: To detect the alleviating effect of bupivacaine polylactic acid microspheres taking high molecular polymer-polylactic acid as vector in rabbits with high performance liquid chromatograph (HPLC) and traditional skin test method.DESIGN: A completely randomized controlled animal experimental study.SETTING: School of Pharmacy, Second Military Medical University of Chinese PLAMATERIALS: Sixteen New Zealand rabbits, weighing (2.58±0.17)kg were used in this experiment.INTERVENTIONS: The experiment was carried out at the Department of pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA between September and November 2002. ① Animal models were established according to traditional skin test method. ② Totally 16 New Zealand rabbits were randomly divided into 2 groups: Group A and Group B, with 8 in each one. 5 mg/kg bupivacaine parenteral solution was injected subcutaneously in Group A, 5 mg/kg bupivacaine polylactic acid microspheres were implanted between subcutaneous tissue and sarcolemma in Group B. We took 1.5 mL blood from ear border vein at 5, 10, 20, 30,45 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after administration of bupivacaine parenteral solution respectively in Group A and another 1.5 mL at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 3 6, 48 and 60 hours after admistration of bupivacaine microsphere powder for index detection. ③ HPLC method was used to detect the concentration and releasing effect of bupivacaine in blood serum.MAIN OUTCOME MEASURES: Concentration change of bupivacaine in blood serum and efficacy diameter of local anesthetic.RESULTS:All the 16 rabbits entered the stage of result analysis. ①Change of bupivacaine concentration: Plasma bupivacaine concentration in Group A reached the peaked quickly after subutaneous injection with the high concentration of 2.466 4 mg/L, then declined quickly. Plasma bupivacaine concentration in Group B was relative stable, reached a peak much slowly after subcutaneous implantation, with peak concentration of 0.778 1 mg/L, and the plasma bupivacaine concentration maintained a relative low level, the mean retention time was obviously prolonged (P ＜ 0.05).② Alleviating effect of bupivacaine: The analgesic time was significantly longer in the bupivacaine microsphere group than in the bupivacaine parenteral solution group (P ＜ 0.05).CONCLUSION:Bupivacaine polylactic acid microspheres have sustained release effects in rabbits.
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Objective: To design a biodegradable aerosol film for treating various wound and diffuse hemorrhage in various organs. Methods: Uniform design was used to screen prescription. Ultraviolet spectrophotometry was used to assay the release in vitro . Results: Time of film formation was less than 30 s. The release in vitro was about 50% in 15 min and stabilized gradually after 15 min. Conclusion:The film formation and release in vitro are well acceptable. [
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Pulsed drug delivery(PDD),which can be released at well-defined time points as the therapy needs,can decrease the frequency and avoid taking drug at night,thus improving patient compliance.Here we introduce three kinds of programmed PDD systems independent of external chemical triggering;they are divided according to the triggering mechanisms:degradation-triggered PDD,osmotic pressure-triggered PDD,and both degradationi and osmotic pressure-triggered PDD.This paper reviews preparing technique,release mechanisms and influencing factors of the three PDD systems.The release profiles of pulsatile PDD can be regulated for different therapeutic needs,requiring no external triggers;especially that the PDD system triggered by both degradation and osmotic pressure has a bright future.
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Objective To evaluate the pharmacokinetics and pharmacodynamics of bupivacaine polylactic acid microspheres in rabbits. Methods Sixteen New Zealand rabbits weighing (2.58?0.17) kg were randomly divided into two groups:in group A a bolus of bupivacaine solution 5 mg?kg-1 was injected subcutaneously, in group B a bolus of bupivacaine polylactic acid microspheres 5 mg ? kg-1 was implanted in subcutaneous tissue. Blood samples were obtained for determination of plasma bupivacaine concentration at 5,10,20,30,45 min and 1,2,3,4, 6,8,12,24h after subcutaneous injection in group A and at 0.5,1,2,3,4,5,6,8,12,24,36,48 and 60 h after subcutaneous implantation in group B. Pharmacodynamics study was conducted using a model evaluating the efficacy of regional anesthesia by skin incision and needle pricking. Results In group A plasma bupivacaine concentration peaked quickly at about 0. 34h after subcutaneous injection, then quickly declined and became indetectable in plasma within 12 h. In group B plasma bupivacaine concentration reached a peak much slowly at about 13h after subcutaneous implantation. Cmax was 0.7781 ? 0.3573 ?g?ml-1 significantly lower than that in group A [Cmax = (2.4664 ? 0.7822) ?g?ml-1 ] . The mean retention time (MRT) was 25.2667 ? 2.4857 h, significantly longer than that in group A [MRT= (5.5580 ? 1.3843)h] . Pharmacodynamic study showed that the duration of regional sensory block was significantly longer in group B than that in group A( P
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AIM: To investigate the antioxidative and antinitrosative effects of copperleaf(Acalypha australis L) on TNBS-induced ulcerative colitis rats. METHODS: Using biochemical method,the activity of antioxidative enzyme SOD,GSH-Px and MDA were determined in normal,model and three rat's groups with low,moderate and high copperleaf decoction respectively.At the same time,the production of NO and the activity of iNOS were also measured.The expression of iNOS mRNA was also determined in normal,model and moderate-copperleaf decoction rats groups through RT-PCR method. RESULTS: The index SOD and GSH-Px increased and MDA reduced significantly in high-and moderate-copperleaf decoction groups compared with the model group.The production of NO the activity of iNOS reduced significantly in high-and moderate-copperleaf decoction groups compared with the model group.RT-PCR results demonstrated that the expression of iNOS mRNA was significantly inhibited in TNBS-induced ulcerative colitis rats after being treated with moderate-dosage copperleaf. CONCLUSION: Acalypha australis L.has antioxidative and antinitrosative effects which is probably one of the mechanism of copperleaf for treating UC.
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Objective:To observe the stability of thymosin ?_1 microspheres under preparation conditions.Methods: Using HPLC method,we investigated the influence of different temperatures(-20 ℃, 6-8℃,60℃),sonification time(10-60 s) and pH values (pH 4.0,7.0 and 10.0) on thymosin ?_1 stability.Results: Under the conditions of frozen environment(-20℃) and refrigeration(6-8℃), thymosin ?_1 remained stable for 30 d.Thymosin ?_1 did not degrade in 60℃ water bath for 12 h or in phosphate buffer solution(PBS,pH 4.0) under 37℃ for 14 h.The sonification time within 60 s was found to be safe for the preparation.Conclusion: Thymosin ?_1 is stable under these preparation conditions.
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Objective: To prepare sustained-release polylactic acid microspheres containing bupivacaine (BUP-PLA-MS) and to measure its dissolution in vitro. Methods: BUP-PLA-MS was prepared with polylactic acid (PLA) as carriers using the water-in-oil-in-water (W/O/W) emulsion solvent evaporation method. The powder particle characteristics of BUP-PLA-MS were evaluated comprehensively, and its dissolution characteristics in vitro were studied. Results: It was indicated that bupivacaine formed molecular dispersion within PLA matrix by differential thermal analysis(DTA). The in vitro release behavior of bupivacaine could be best described by Higuchi equation, with t 1/2 =22.76 h. Conclusion: Release of bupivacaine from microspheres is sustained in vitro.
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Objective:To prepare injectable interferon ?-2b(IFN-?-2b) loaded microsphere and develop a long-acting dosage form.Methods: IFN-?-2b loaded microspheres were prepared with poly(lactic-co-glycolic acid)(PLGA) as carrier material by double emulsion(w/o/w) method and solid in oil in oil(s/o/o) method separately.Physical and chemical characteristics of microspheres(mean diameter,morphology and drug entrapment efficiency) were evaluated;the in vitro release behavior and influencing factors of the microspheres were determined by micro-BCA(bicinchoninic acid) method;and IFN-?-2b stability during encapsulation and in vitro release was evaluated by sodium dodecyl sulfate polyacrylamide gel electropheresis.Results: The 2 types of microspheres produced had good shape and dispersive quality and a drug entrapment efficiency of more than 80%.IFN-?-2b bulk ultrafitration can significantly influence the mean diameter and in vitro release behavior of microspheres prepared by w/o/w method.The accumulated release(within 1 month) of the microspheres prepared by both methods was significantly improved when using PLGA with lower inherent viscosity.SDS-PAGE test showed aggregation of IFN-?-2b with s/o/o method,while there was no difference between the electrophoretic behavior of bulk IFN-?-2b and IFN-?-2b in microspheres prepared by w/o/w method.Conclusion: IFN-?-2b can be encapsulated into injectable microspheres to yield a one-month continuous release by both w/o/w method and s/o/o method.