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.

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.

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. [

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.

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.

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.

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.

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.

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.

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