双氯芬酸钠柔性脂质体的制备及其对离体小鼠皮肤的透皮效果

利用同离子效应制备双氯芬酸钠柔性脂质体,并考察脂质浓度对包封率的影响.同时比较了双氯芬酸钠乳膏、传统脂质体与柔性脂质体对离体小鼠皮肤的透皮效果.结果表明,同离子效应可显著增大柔性脂质体的包封率,较理想的脂质浓度为卵磷脂-胆酸钠为6∶1.2(g,w/w),离体小鼠皮肤12h累积透过率依次为:柔性脂质体＞＞传统脂质体＞乳膏.     

硝酸益康唑外用脂质体的制备

通过正交设计筛选硝酸益康唑脂质体处方,并考察了产品的形态、粒径、结晶状态、黏度和表面电位等物理性质.硝酸益康唑脂质体为球型结构,平均粒径118.1nm,电位 65.3mV,黏度3.3mPa·s[(32±1)℃];脂质体凝胶的黏度为7.9166Pa·s[(32±1)℃],两者表面均无药物晶体吸附.     

注射用柴胡挥发油脂质体制备工艺研究

目的 :探讨将柴胡挥发油制成注射用脂质体的制备工艺可行性。方法 :通过研究柴胡挥发油脂质体的处方组成、挥发油包封率、冻干可行性以及二者的指纹图谱变化。结果 :柴胡挥发油的包封率为 81.9%。经冷冻干燥后 ,脂质体中被包封挥发油的保留率为 88.6 %。结论 :将柴胡挥发油制备成注射用脂质体在制备工艺上是可行的。     

HIF1α-siRNA and gemcitabine combination-based GE-11 peptide antibody-targeted nanomedicine for enhanced therapeutic efficacy in pancreatic cancers

Abstract

Pancreatic cancer is one of the deadliest cancers across the world with an average 5-year survival rate of less than <6%. In this study, gemcitabine (GEM) and HIF1α-siRNA loaded GE-11 peptide conjugated liposome was successfully prepared and evaluated for its antitumor efficacy in pancreatic cancer cells. The GE11 increased the targeting specificity of liposome carrier and increased the intracellular concentrations in the cancer cells. Furthermore, synergistic combination of GEM and HIF1a-siRNA exhibited remarkable improvement in the declining of cancer cell proliferations. siRNA could effectively decrease the expression of HIF1a gene in the cancer cells. Importantly, GE-11 peptide-conjugated GEM/siRNA-loaded liposomes (GE-GML/siRNA) increased the total amount of apoptosis cells with higher proportion of cells in late apoptosis phase. GE-GML induced remarkable apoptosis of cancer cells and induced chromatin condensation and nuclear fragmentation which are considered to be typical features of apoptosis and cell death. GE-GML/siRNA showed a significant reduction in the tumour burden suggesting the superior anticancer efficacy of this formulation. GE-GML/siRNA showed four-fold reduction in tumour compared to control and two-fold reduction compared to GE-GML, respectively. Overall, present work lays foundation for the combination of GEM and HIF1a-siRNA loaded in a targeted nanocarrier system as a unique therapeutic option in pancreatic cancer treatment.     

Utility of Flexible Bronchoscopy in the Evaluation of Pulmonary Infiltrates in the Hematopoietic Stem Cell Transplant Population – A Single Center Fourteen Year Experience

IntroductionPulmonary infiltrates are common within the hematopoietic stem cell transplant (HSCT) population and unfortunately portend an increased mortality. Bronchoscopy is often utilized as an initial diagnostic tool, but the literature supporting its diagnostic utility and effect on clinical management varies significantly. The aim of this study was to investigate the diagnostic ability, complication rate, and clinical impact of flexible bronchoscopy (FB) in evaluating pulmonary infiltrates in a large HSCT population.Patients and methodRetrospective review of all patients undergoing FB after HSCT in the Bone Marrow Transplant Unit from 1996 to 2009.ResultsFB was performed 162 times in 144 patients with pulmonary infiltrates yielding positive results in 52.5%. The most common positive results were bacterial pneumonia (31%), fungal pneumonia (15%), and alveolar hemorrhage (11%). Treatment changes occurred in 44% of patients after FB. Treatment changes included antibiotic modification (59%), addition of corticosteroids (21%), antifungal modification (12%), and antiviral modification (7%). The overall complication rate associated with FB was 30%, although 84% of these complications were considered minor.ConclusionsFB in patients with pulmonary infiltrates after HSCT should still be considered a valuable tool in the evaluation and management of pulmonary infiltrates in the HSCT population. Future prospective, multicenter randomized studies are needed to evaluate the overall clinical impact that bronchoscopic results and management changes have in this unique population.     

膀胱软镜在复杂性肾结石开放手术中的应用

目的：探讨膀胱软镜在复杂性肾结石开放手术中的应用价值。方法：将膀胱软镜应用于复杂性肾结石开放手术中辅助结石取出及检查28例，术中经膀胱软镜探查，并配合钳夹冲洗肾盏切开等方法取出结石。结果：28例均获得成功，术后行B超及X片复查，仅2例结石残留。结论：肾多发结石开放手术中配合膀胱软镜检查可以提高手术成功率，减少结石残留率，减少对患者损伤，是一种安全有效的方法，同时还能对其他病变起到检查及治疗作用。     

In vitro and in vivo investigation of glucose-mediated brain-targeting liposomes

New glycosyl derivative of cholesterol was synthesized as a material for preparing novel liposome to overcome the ineffective delivery of normal drug formulations to brain by targeting the (glucose transporters) GLUTs on the BBB. Coumarin-6 was used as fluorescent probe. The results have shown that the cytotoxicity for the brain capillary endothelial cells (BCECs) of the glucose-mediated brain targeting liposome containing coumarin-6 was less than that of conventional liposome. The BBB model in vitro was established by coculturing of BCECs and astrocytes (ACs) of rat to test the transendothelial ability crossing the BBB. The transendothelial ability was confirmed strengthen alone with the amount of the new glycosyl derivative of cholesterol used in liposome. After i.v. administration of LIP, control liposome (CLP), and GLP-4, the AUC_0–t of coumarin-6 for GLP-4 was 2.85 times higher than that of LIP, and 3.33 times higher than that of CLP. The C_max of CLP-4 was 1.43 times higher than that of LIP, and 3.10 times higher than that of CLP. Both pharmacokinetics and distribution in mice were also investigated to show that this novel brain targeting drug delivery system was promising.     

气管切开后拔管困难原因分析及处理

目的探讨可弯曲支气管镜(纤维支气管镜/电子支气管镜,简称支气管镜)在气管切开术后拔管困难诊治中的意义。方法回顾性分析17例经可弯曲支气管镜检查确诊和治疗的气管切开术后拔管困难患者的临床资料。结果 17例拔管困难患者,除1例脑外伤气管上端瘢痕挛缩伴闭锁拔管失败外;其余16例患者均成功拔管,拔管成功率94.1%。除1例患者出现支架移位、1例患者拔管后出现呼吸困难外,余无不良事件发生,无致死性并发症发生。结论可弯曲支气管镜在气管切开术后拔管困难患者诊治中起着重要作用,且安全可靠,值得临床推广。     

Enhanced Tumor Targeting of Doxorubicin by Ganglioside GMl-bearing Long-circulating Liposomes

Abstract

Doxorubicin (DXR) was encapsulated in long-circulating liposomes, composed of ganglioside GM1 (GM1)/distearoylphosphatidylcholine (DSPC)/cholesterol (CH) (0.13:1:1 in molar ratio) and sized to approximately 100 nm in mean diameter, with 98% entrapping efficiency by the transmembrane pH gradient method. Free DXR, DXR-DSPC/CH and DXR-GM1/DSPC/CH liposomes were injected intravenously into Colon 26 tumor-bearing Balb/c mice via the tail vein at a dose of 5.0 mg DXR/kg. DXR-GM1/DSPC/CH liposomes gave a higher blood level of the drug than did DXR-DSPC/CH liposomes or free DXR up to 24 hours after injection, and the area under the blood concentration-time curve (AUC) for DXR-GM1/DSPC/CH liposomes was 1.5 or 526 times higher than that for DXR-DSPC/CH liposomes or free DXR, respectively. DXR-GM1/DSPC/CH liposomes gave a decreased DXR concentration in the reticuloendothelial system (RES) of the liver and the spleen. Both liposomal formulations effectively reduced the DXR concentration in the heart as compared with that in the case of free DXR. At 6 hours after i.v. injection, DXR-GM1/DSPC/CH liposomes provided an approximately 3.3- or 9-fold higher peak DXR level in the tumor as compared with DXR-DSPC/CH liposomes or the free drug, respectively. These high tumor levels of DXR appear to reflect the prolonged residence time of the liposomes. The results suggest that encapsulation of DXR in GM1-bearing long-circulating liposomes will be useful for cancer chemotherapy.     

Liposome bupivacaine in peripheral nerve blocks and epidural injections to manage postoperative pain

Solifenacin is an antimuscarinic agent, administered once daily, which has been newly approved for the treatment of overactive bladder (OAB). Solifenacin administered at 5- and 10-mg once-daily doses shows efficacy for all the symptoms of OAB in both ‘wet’ and ‘dry’ patients, including improvements in patient quality of life and satisfaction. These improvements are observed as early as week 2 of treatment and are maintained over 12-week and 1-year time periods, without being compromised by the age or gender of the patient. Solifenacin demonstrates a favourable tolerability profile, with mild dry mouth as the most common adverse event associated with its use, both at the 5- and 10-mg doses; this allows for flexibility in the dosing regimen, in which physicians can administer solifenacin 5 mg, with the option to safely increase the dose to 10 mg if necessary based on the severity of patient’s symptoms. The favourable efficacy and safety profile of solifenacin, coupled with its dose flexibility, are consistent with solifenacin being a convenient treatment option for patients with OAB.