表面活性剂泊洛沙姆188临界胶束浓度的模拟计算

建立了一种介观模拟计算表面活性剂临界胶柬浓度（CMC）的方法。以非离子表面活性剂泊洛沙姆188为研究对象，计算了其在298K下的临界胶束浓度（CMC），分析了泊洛沙姆188在水中相行为和有序参数的变化，为表面活性剂增溶作用的研究提供了基础。     

新型药用辅料—泊洛沙姆407急性毒性初步研究

目的：了解泊洛沙姆407的急性毒性作用。方法：泊洛沙姆407凝胶昆明小鼠腹腔注射（ip），观察小鼠死亡率及血丙氨酸转移酶（ALT）、尿素氦（BUN）、总胆固醇（CH）及甘油三酯（TG）含量变化。结果：中、小剂量泊洛沙姆407小鼠ip对ALT、BUN无明显影响，但可致血脂一过性增高；小鼠ip25％泊洛沙姆407凝胶5．0g／kg，死亡率为50％。结论：泊洛沙姆407是一个毒性较低的药用辅料。     

Gene transfer mediated by sphingosine/ dioleoylphosphatidylethanolamine liposomes in the presence of poloxamer 188

A cationic liposome system consisting of sphingosine (SP) and dioleoylphosphatidylethanolamine (DOPE) was developed for in vitro and in vivo gene transfer. A nonionic surface active agent of poloxamer 188 was incorporated in the formulations to stabilize the DNA/liposome complex. Comparison of the results obtained from systems with and without the effect of poloxamer 188 was made to investigate the efficiency of gene expression. In vitro transfection study of the DNA/liposome complex showed that with the effect of poloxamer 188, gene transfer into some cell lines was enhanced. In vivo systemic delivery of the DNA/liposome complex with poloxamer 188 demonstrated gene expression with improved luciferase activity in all major organs including lung, spleen, heart, liver, and kidney. High level transgene activity was found in lung and spleen with prolonged gene expression. This was attributed to poloxamer 188 that stabilized the liposome system and produced homogeneous DNA/liposome complex for enhancement of gene delivery.     

瑞舒伐他汀对poloxamer407诱导的小鼠高血脂模型血脂水平的影响

目的观察瑞舒伐他汀对poloxamer 407(P-407)诱导的小鼠高血脂模型血脂水平的影响。方法小鼠于腹腔注射P-407前先以瑞舒伐他汀(2或10 mg/kg)连续灌胃,并于腹腔注射P-407(0.3 g/kg)后3 h再次灌胃瑞舒伐他汀。以注射P-407前及注射后第3、4、24及48 h血甘油三酯和胆固醇水平评价瑞舒伐他汀的疗效,同时观察造模后24 h高密度脂蛋白-胆固醇水平。结果瑞舒伐他汀组血清甘油三酯和胆固醇水平减低,具有显著的量效关系,且作用可持续至造模后的48 h。瑞舒伐他汀组小鼠造模后24 h血清高密度脂蛋白-胆固醇水平显著升高(P<0.05)。结论瑞舒伐他汀可有效降低P-407诱导的高血脂模型小鼠的血脂水平。     

Evaluation of pluronic nanosuspensions loading a novel insoluble anticancer drug both in vitro and in vivo

To improve the solubility, stability and the antitumor activity of a novel anticancer drug, 3-(4-bromopheny l)-2-(ethyl-sulfonyl)-6-methylquinoxaline1,4-dioxide (Q39), a poloxamer nanosuspension was developed by precipitation combined with high pressure homogenization in present study. In vitro characterizations of Q39 nanosuspension (Q39/NS), including particle size, polydispersity index (PI), morphology, crystalline, saturation solubility, stability and releases were evaluated. BABL/c nude mice bearing HepG2 cells were used as in vivo tumor models to evaluate the anti-tumor activity of Q39/NS after intravenous administration. The particle size and PI for Poloxamer188 nanosuspension (P188/NS) were (304 ± 3) nm, and (0.123 ± 0.005) respectively, and it was (307 ± 5) nm and (0.120 ± 0.007) for Poloxamer85 nanosuspension (P85/NS) correspondingly. The morphology of P188/NS was spherical shape while elliptoid shape for P85/NS. The crystalline of Q39/NS did not change as shown by the X-ray diffraction analysis. The stability of Q39/NS improved compared with the solution. The solubility of Q39 in P188/NS was 7.3 times higher than the original solubility, while it was 6 times for P85/NS. Sustained release as shown from the in vitro release test, together with the tumor-targeting as shown from in vivo NS distribution, may contribute to the enhanced in vivo antitumor activity of Q39/NS.     

Thermosensitive Hydrogel Wound Dressing Loaded with Bacteriophage Lysin LysP53

Wound infections are prone to attacks from infectious pathogens, including multidrug resistant bacteria that render conventional antimicrobials ineffective. Recently, lysins have been proposed as alternatives to conventional antimicrobials to tackle the menace of multidrug resistance pathogens. The coupling of lysins with a material that will cover the wound may prove beneficial in both protecting and treating wound infections. Hence, in this study, a Gram-negative lysin, LysP53, was coupled with a thermosensitive hydrogel, poloxamer P407, and its efficacy to treat wound infection was tested. In vitro, the addition of LysP53 to the poloxamer did not affect its thermosensitive characteristics, nor did it affect the hydrogel structure. Moreover, the lysin hydrogel could hydrolyze the peptidoglycan, demonstrating that it may have bactericidal activity. Up to 10.4% of LysP53 was released from the hydrogel gradually within 24 h, which led to a 4-log reduction of stationary phase Acinetobacter baumannii. Lastly, the lysin hydrogel was found safe with no cytotoxic effects observed in cells. Ex vivo, LysP53 hydrogel could inhibit bacterial growth on a pig skin decolonization model, with 3-log differences compared to non-treated groups. Overall, our results suggest that lysin-loaded hydrogels may provide a novel solution to treat wound infections caused by resistant bacteria.     

表面活性剂泊洛沙姆188临界胶束浓度的模拟计算

建立了一种介观模拟计算表面活性剂临界胶束浓度(CMC)的方法。以非离子表面活性剂泊洛沙姆188为研究对象,计算了其在298K下的临界胶束浓度(CMC),分析了泊洛沙姆188在水中相行为和有序参数的变化,为表面活性剂增溶作用的研究提供了基础。     

三元固体分散体提高利多卡因溶解度研究（英文）

使用熔融法制备利多卡因-泊洛沙姆固体分散体以提高利多卡因的溶解度及溶出度。以利多卡因(LIC)作为模型药物,分别使用泊洛沙姆188 (P188)和泊洛沙姆407 (P407)作为单一及混合载体,制备三元及二元固体分散体并进行比较。使用DSC、XRD、SEM及FTIR进行一系列表征,通过溶出度试验研究固体分散体的溶出特性,药物以晶体形式存在于载体中,药物溶出度及溶解度结果较原料药均有明显提高。相溶解度研究显示出药物与载体呈AL型曲线,有分子相互作用的存在。此外,还考察了固体分散体在不同相对湿度下的长期稳定性,稳定性测试结果表明三元及二元利多卡因-泊洛沙姆固体分散体在不同湿度下,6个月内保持稳定。研究结果表明,混合泊洛沙姆三元固体分散体可以显著提高难溶性利多卡因的溶出度和溶解度。     

姜黄提取物固体分散体的制备及体外评价

目的 制备共聚维酮-泊洛沙姆姜黄提取物固体分散体[PVP/VA-Poloxamer-Curcumae Longae Rhizoma extract (CLRE)solid dispersion (SD),PAP-CSD]、共聚维酮姜黄提取物固体分散体(PVP/VA CLRE solid dispersion,PA-CS...     

Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17 min of untreated cardiac arrest

ObjectiveIschemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 min of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest.MethodsFollowing 17 min of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n = 8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n = 12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score.ResultsBundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 h), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 h).ConclusionsBundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 min of untreated cardiac arrest in pigs.All studies were performed with approval from the Institutional Animal Care Committee of the Minneapolis Medical Research Foundation (protocol #12-11).