主动靶向脂质体研究进展

目的 介绍主动靶向脂质体最新研究进展。方法 查阅近年来国内外相关文献,对主动靶向脂质体的表面修饰、配体选择及应用进行进行总结和归纳。结果 主动靶向脂质体的表面修饰有三种方法：作为组份直接制备;键合到脂质体表面;后插入法。主动靶向脂质体可以将药物传递到靶组织、靶向细胞或靶细胞器,提高药物的生物利用度,而不增加对正常组织或细胞的毒性,是近年研究最为广泛的主动靶向给药系统。结论 主动靶向脂质体是一种非常有前途的给药系统。     

脂质体修饰性材料应用研究进展

脂质体作为低毒性与免疫原性的药物载体已被应用于难溶性、不稳定、毒性等药物的递送,但传统脂质体仍存在稳定性差、体内循环时间不足、主动靶向性不明显等缺陷,因此选择适宜的修饰性材料制备脂质体已成为必要手段。修饰脂质体的方法主要有：在膜材中加入表面活性剂或改性物质,在膜表面嵌插靶向配体物质,将配体与膜材偶联共同组成脂质体结构。通过总结近年来脂质体常用的修饰性材料,阐释修饰原理并分析其优势及弊端,为脂质体的研究与开发提供借鉴。     

头孢丙烯治疗细菌性感染31例

目的:评价头孢丙烯的疗效及安全性.方法:以头孢丙烯和头孢克洛随机对照治疗急性轻、中度呼吸道及皮肤软组织感染,31例患者接受头孢丙烯(250～500 mg,2次/d)、35例患者接受头孢克洛(250～500 mg,3次/d)治疗,疗程7～14 d.结果:治疗组和对照组的痊愈率和总有效率分别为77.4%,80.0%(P＞0.05)与96.8%,94.3%(P＞0.05);细菌阳性率、清除率分别为87.1%,88.6%(P＞0.05)和96.3%,93.5%(P＞0.05);不良反应发生率分别为4.7%和4.3%(P＞0.05).结论:头孢丙烯治疗轻、中度细菌感染安全、有效.     

Shortened Courses of Antibiotics for Bacterial Infections: A Systematic Review of Randomized Controlled Trials

Commonly prescribed durations of therapy for many, if not most, bacterial infections are not evidence‐based. Misunderstandings by clinicians and patients alike influence perspectives on antibiotic use, including duration of therapy and its role in antibiotic resistance. To demonstrate that shorter durations of antibiotic therapy are as efficacious as longer durations for many infections, a systematic review was undertaken of English‐language articles by using PubMed to identify articles for inclusion. Additionally, infection‐specific guidelines were identified for review of recommendations. Search terms included specific infection types, randomized controlled trial (RCT), duration of therapy, treatment duration, short course, and long course. Only RCTs of single‐agent antibiotic therapy for the treatment of bacterial infections in adults were included. Independent data extraction of articles was conducted by two authors by using predefined guidance for article inclusion. In total, 23 RCTs met our criteria for inclusion. All trials compared single‐agent antibiotics for a short and long antibiotic course in six common infections: community‐acquired pneumonia, ventilator‐associated pneumonia, intraabdominal infections, skin and soft tissue infections, uncomplicated cystitis, and complicated cystitis or pyelonephritis. Clinicians can decrease net antibiotic use by recommending shorter courses where evidence supports them. Antimicrobial stewardship programs that systematically address treatment duration may significantly affect institutional antibiotic use without negatively affecting patient care.     

司帕沙星与氧氟沙星治疗老年呼吸道细菌感染

目的:对照研究司帕沙星(SPFX)与氧氟沙星(OFLX)治疗老年患者呼吸道细菌感染(RTBI)的临床疗效及安全性。方法:将120例呼吸道细菌感染的老年患者随机分入试验(T)组和对照(C)组。试验组给予司帕沙星口服300mg,1次/d,对照组给予氧氟沙星口服200mg,2次/d。疗程均为7～10d。结果:试验组的综合疗效显著优于对照组(P<0.01),试验组痊愈率为71.7%,有效率为95.0%,均显著高于对照组(均P<0.05);试验组不良反应为3.33%,对照组不良反应为6.67%。结论:司帕沙星治疗老年患者呼吸道细菌感染疗效肯定、安全。     

Liposomes in the Treatment of Infections

Abstract

The use of liposomes in the treatment of severe infections is under investigation. Classical liposomes which localize in cells of the mononuclear phagocyte system (MPS) can be exploited in two ways. First for targeting of macrophage modulators such as muramyl peptides or IFN-γ, to stimulate the cells of the MPS to maximal blood clearance capacity. This enhanced nonspecific anti-infectious resistance is important as in immunocompromised patients micro-organisms frequently appear in the blood from a local infection. Secondly, classical liposomes are successfully used as carriers of antibiotics in experimental intracellular parasitic-, viral-, fungal- or bacterial infections in MPS tissues. Based on these data extensive studies in patients with severe fungal infections have demonstrated successful treatment with liposomal or lipid-complexed amphotericin B. More recently, liposomal amphotericin B appeared to be effective in patients with drug-resistant visceral leishmaniasis. For the treatment of Mycobacterium avium complex infection in AIDS patients the efficacy of liposomal gentamicin is under investigation. With respect to infections in non-MPS tissues the applicability of Stealth® liposomes characterized by long circulation half-lives is under investigation. Substantial localization of these liposomes in infected lung tissue of rats was demonstrated. Preliminary data in experimental bacterial lung infection showed superior efficacy of antibiotic encapsulated in Stealth® liposomes.     

头孢吡肟与头孢他啶治疗细菌性感染分析

目的：比较头孢吡肟与头孢他啶治疗细菌性感染的药物经济学成本－效果。方法：选择129例患者随机分为头孢吡肟组65例,每次2g,bid 治疗尿路感染每次1g bid;头孢他啶组64例,每次2g,tid,治疗尿路感染每次1g,tid,均静脉滴注,疗程平均11d,采用药物经济学成本－效果分析法。结果：头孢吡肟,头孢他啶治疗细菌性感染有效率分别为92．3％,90．6％,痊愈率分别为72．3％,68．8％,4种类型细菌性感染头孢吡肟成本－效果比均低于头孢他啶,结论：头孢吡肟治疗细菌性感染经济效益 于头孢他啶。     

Liposomes and their applications in molecular imaging

Molecular imaging is a relatively new discipline with a crucial role in diagnosis and treatment tracing of diseases through characterization and quantification of biological processes at cellular and sub-cellular levels of living organisms. These molecular targeted systems can be conjugated with contrast agents or radioligands to obtain specific molecular probes for the purpose of diagnosis of diseases more accurately by different imaging modalities. Nowadays, an interesting new approach to molecular imaging is the use of stealth nanosized drug delivery systems such as liposomes having convenient properties such as biodegradability, biocompatibility and non-toxicity and they can specifically be targeted to desired disease tissues by combining with specific targeting ligands and probes. The targeted liposomes as molecular probes in molecular imaging have been evaluated in this review. Therefore, the essential point is detection of molecular target of the disease which is different from normal conditions such as increase or decrease of a receptor, transporter, hormone, enzyme etc, or formation of a novel target. Transport of the diagnostic probe specifically to targeted cellular, sub-cellular or even to molecular entities can be performed by molecular imaging probes. This may lead to produce personalized medicine for imaging and/or therapy of diseases at earlier stages.     

2012-2015年昆明地区儿童血源性感染细菌谱及耐药特点

目的:了解昆明地区2012-2015年儿童血源性感染细菌构成及耐药特点。方法:收集2012-2015年昆明市儿童医院住院患儿送检的血培养标本共37 505例,采用BACT ALERT 3D全自动血培养仪检测,按照《全国临床检验操作规程》鉴定细菌菌种。药敏试验采用纸片扩散法,结果按美国国家临床实验室标准委员会(NCCLS)2000年版标准判断。结果:37 505例血培养标本共检出细菌1 240株,检出率3.3%,前5位检出细菌依次为凝固酶阴性葡萄球菌、大肠埃希菌、金黄色葡萄球菌、肺炎克雷伯菌、沙门菌。凝固酶阴性葡萄球菌耐甲氧西林菌株检出率为81.5%(327/401),耐甲氧西林金黄色葡萄球菌检出率为20.0%(8/40),产ESBLs大肠埃希菌检出率为51.4%(92/179),产ESBLs肺炎克雷伯菌检出率为63.2%(42/66)。金黄色葡萄球菌对青霉素的耐药率为100%,对苯唑西林及头孢唑林的耐药率呈下降趋势,对红霉素及克林霉素不同程度耐药;凝固酶阴性葡萄球菌对青霉素、苯唑西林、头孢唑林、红霉素、克林霉素耐药率较高;未检出对万古霉素耐药菌株。大肠埃希菌和肺炎克雷伯菌对氨苄西林、头孢唑林、哌拉西林、头孢噻肟的耐药率较高,其ESBLs(+)菌株中甚至检出对亚胺培南或美罗培南的耐药菌株;沙门菌对常用抗生素的耐药率均较低。结论:昆明地区2012-2015年儿童血源性感染细菌以凝固酶阴性葡萄球菌、大肠埃希菌、金黄色葡萄球菌、肺炎克雷伯菌、沙门菌为主,治疗应结合本地区近年来的病原菌谱及耐药特点,合理使用抗菌药物,减少耐药菌株的产生。     

氟罗沙星治疗细菌性感染62例

目的:观察氟罗沙星葡萄糖注射液治疗细菌感染性疾病的临床疗效及安全性.方法:选取呼吸道感染患者30例及尿路感染患者32例,给予氟罗沙星0.2～0.4 g,静脉滴注,qd,疗程7～14 d.结果:氟罗沙星治疗呼吸道感染的有效率93.3%,治疗尿路感染的有效率96.9%,患者均未出现严重的不良反应.结论:氟罗沙星葡萄糖注射液是一种疗效确切、不良反应小的抗菌药物.     

Advances in Targeting Drug Delivery to Glomerular Mesangial Cells by Long Circulating Cationic Liposomes for the Treatment of Glomerulonephritis

Purpose Newly designed polyethylene glycol (PEG)-modified cationic liposomes, containing a novel cationic lipid TRX-20 (3,5-dipentadecyloxybenzamidine hydrochloride), bind specifically to cultured human mesangial cells, and not to endothelial cells. In this study, we investigated targeting the delivery of PEG-modified liposomes containing TRX-20 (TRX-liposomes) to mesangial cells and evaluated their pharmacokinetic behavior in a rat experimental glomerulonephritis model, using prednisolone phosphate (PSLP) as a model drug. Material and Methods TRX-liposomes were injected intravenously into experimental glomerulonephritic rats and normal rats to compare its pharmacokinetic behavior with that of non-cationic liposomes (PEG-liposomes). Rhodamine-labeled liposomes were used to evaluate the accumulation in inflamed kidneys. Pharmacological effects of three formulations of PSLP (i.e., a single injection of two liposomal formulations and daily injections of PSLP in saline solution) were estimated in terms of suppressing glomerular cell proliferation in the rat nephritis model. Results TRX-liposomes markedly accumulated in the glomeruli of inflamed kidneys, but did not accumulate in the glomeruli of normal kidneys. Although the PEG-liposomes also accumulated in the glomeruli of the inflamed kidneys, their pharmacological behavior was quite different from that of the TRX-liposomes, which were internalized by the target cells. In a comparison among the three formulations of PSLP, the dose of TRX-liposomes required for significant suppression of glomerular cell proliferation was much less (dose of 0.032 mg/kg and above) than that required for the same effect by the PSLP saline solution (3.2 mg/kg daily; 12.8 mg/kg total) and PEG-liposomes (0.32 mg/kg). Interestingly, significant suppression of mesangial cell activation, as assessed by the expression of α-smooth muscle actin, was observed in nephritic rats treated with TRX-liposomes, but not in the other two treatment groups. Conclusions The pharmaceutical properties of TRX-liposomes due to their preferential binding to mesangial cells and long circulation time make this a likely candidate system for targeted drug delivery to the inflamed glomeruli of glomerulonephritis.     

Adenosine Triphosphate Liposomes: Encapsulation and Distribution Studies

Four methods for encapsulating adenosine triphosphate (ATP) in liposomes were evaluated. Optimum entrapment required emulsifying ATP with the lipids used to form the liposome membrane in a high-speed homogenizer followed by evaporating the organic solvent with vigorous stirring. Under these optimum conditions ATP entrapment was 38.9%; i.e., the dosage form contained 38.9 g of ATP per 100 g of lipid. The distribution of positively charged liposomes loaded with ATP was studied in dogs with experimentally induced myocardial infarction. Intravenous injection of positively charged ATP liposomes caused accumulation of ATP in myocardial infarct tissue. Myocardial infarct tissue has reduced blood flow; since positively charged liposomes accumulated in infarct tissue, liposomes may be a drug delivery system for this disease state.     

氟罗沙星治疗细菌性感染的药物经济学研究

目的:评价氟罗沙星和氧氟沙星治疗细菌性感染的经济性.方法:治疗组患者35例,使用氟罗沙星0.3 g,静脉滴注,1次/d共10.5 d;对照组患者32例,使用氧氟沙星0.3 g,静脉滴注,2次/d,共10.5 d.运用药物经济学的成本-效果分析方法进行评价.结果:2种方案的成本-效果比(C/E)分别为22.87,20.43,效果(以有效率表示)分别为91%,84%(P＞0.05).结论:氧氟沙星经济性最佳,氟罗沙星市场价格太贵,建议厂商重新考虑市场的药品定价策略.     

国产和进口美罗培南治疗急性细菌性感染的疗效分析

目的评价国产与进口美罗培南治疗急性细菌性感染的有效性与安全性。方法将急性细菌性感染患者54例随机分为两组，治疗组28例用国产美罗培南治疗，对照组26例用进口美罗培南治疗，给药方案均为每次给药0．5g，静脉滴注，每8h一次，疗程均为7d。结果治疗组和对照组的临床有效率分别为89．3％和92．3％，细菌清除率分别为76．9％和80．0％，不良反应发生率分别为10．7％和7．7％。经统计学处理均无显著性差异（P〉0．05）。结论国产和进口美罗培南治疗急性细菌性感染性疾病均有效、安全，国产品可以替代进口品，用于临床严重感染痰病的治疗。     

Enhanced Intracellular Uptake of Sterically Stabilized Liposomal Doxorubicin <Emphasis Type="Italic">in Vitro</Emphasis> Resulting in Improved Antitumor Activity <Emphasis Type="Italic">in Vivo</Emphasis>

Purpose To investigate the correlation between the in vitro intracellular uptake and the in vivo antitumor activity of anticancer drugs delivered by sterically stabilized liposomes (SSL).Methods Arginine-glycine-aspartic acid (RGD) peptide or RGD mimetic (RGDm) was coupled onto the surface of SSL to obtain the cell-binding carrier to facilitate the intracellular delivery of the encapsulated drugs. DOX-loaded SSL (SSL-DOX), DOX-loaded RGD-modified SSL (RGD-SSL-DOX) and DOX-loaded RGDm-modified SSL (RGDm-SSL-DOX) were prepared by lipid film dispersion followed by remote loading of DOX. The intracellular uptake of DOX from the various liposomal formulations was evaluated in vitro with melanoma B16 cells, and the pharmacokinetics, biodistribution, and antitumor activity were compared in C57BL/6 mice carrying melanoma B16 tumors.Results In vitro intracellular uptake of DOX by B16 cells and in vivo antitumor activity in terms of tumor growth inhibition and mice survival time prolongation for various liposomal DOX were in the following order: RGD-SSL-DOX > RGDm-SSL-DOX > SSL-DOX. The mean survival time of the mice treated with RGD-SSL-DOX, RGDm-SSL-DOX, and SSL-DOX was 55, 49, and 44 days, respectively. The three liposomal DOX formulations produced very close DOX accumulation in tumor, which is significantly higher than that of free DOX. RGD- or RGDm-SSL-DOX demonstrated prolonged circulation time similar to that of SSL-DOX, whereas they showed significantly lower DOX level in blood and remarkably higher uptake by spleen than SSL-DOX.Conclusions Enhanced intracellular uptake of DOX encapsulated in SSL could produce an improved therapeutic effect for the melanoma B16 tumors. Enhancing intracellular delivery of the anticancer drugs encapsulated in SSL may be a promising strategy to improve their therapeutic efficacy for solid tumors.     

加替沙星葡萄糖注射液治疗细菌性感染22例

目的:评价加替沙星治疗细菌性感染的临床疗效和安全性.方法:将43例患者随机分为治疗组22例和对照组21例,分别静脉滴注加替沙星葡萄糖注射液和左氧氟沙星注射液,剂量均为0.2 g,2次/d,疗程7～14 d.结果:加替沙星和左氧氟沙星的临床有效率分别为81.82%和80.95%,细菌清除率分别为84.21%和88.24%,无显著性差异(P均＜0.05),两组不良反应发生率分别为9.3%和4.76%,试验中未见光敏反应及其他严重不良反应.结论:加替沙星葡萄糖注射液可作为治疗细菌性感染有效、安全的抗生素.     

Liposomes,a promising strategy for clinical application of platinum derivatives

Introduction: Liposomes represent a versatile system for drug delivery in various pathologies. Platinum derivatives have been demonstrated to have therapeutic efficacy against several solid tumors. But their use is limited due to their side effects. Since liposomal formulations are known to reduce the toxicity of some conventional chemotherapeutic drugs, the encapsulation of platinum derivatives in these systems may be useful in reducing toxicity and maintaining an adequate therapeutic response.

Areas covered: This review describes the strategies applied to platinum derivatives in order to improve their therapeutic activity, while reducing the incidence of side effects. It also reviews the results found in the literature for the different platinum-drugs liposomal formulations and their current status.

Expert opinion: The design of liposomes to achieve effectiveness in antitumor treatment is a goal for platinum derivatives. Liposomes can change the pharmacokinetic parameters of these encapsulated drugs, reducing their side effects. However, few liposomal formulations have demonstrated a significant advantage in therapeutic terms. Lipoplatin, a cisplatin formulation in Phase III, combines a reduction in the toxicity associated with an antitumor activity similar to the free drug. Thermosensitive or targeted liposomes for tumor therapy are also included in this review. Few articles about this strategy applied to platinum drugs can be found in the literature.     

我院感染常见细菌分布及其对抗菌药物耐药性分析

目的:了解医院感染致病菌分布的临床特点及其耐药性情况.方法:对2003年11月～2004年¨月临床标本中分离的细菌进行鉴定及药物敏感试验,并作统计分析.结果:分离细胞中排在前列的为肺炎克雷伯菌、大肠埃希菌、金黄色葡萄球菌,其中大肠埃希菌、肺炎克雷伯菌主要来源于痰、尿;革兰氏阴性菌对头孢噻肟、头孢曲松等耐药率较高,革兰氏阳性菌对克拉霉素、红霉素等耐药率较高;白色念珠菌对酮康唑、咪康唑的耐药率均超过了50%.结论:了解医院感染常见致病菌的分布和耐药趋势,进行耐药性监测,对指导临床合理应用抗菌药物是必要的.     

Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo

Purpose. The purpose of this study was to determine the usefulness of transferrin (TF)-pendant-type polyethyleneglycol (PEG)-liposomes (TF-PEG-liposomes), in which TF was covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes as a carrier for in vivo cytoplasmic targeting to tumor cells. Methods. Small unilamellar TF-PEG-liposomes (100-140 nm in diameter) were prepared from DSPC, CH, DSPE-PEG, and DSPE-PEG-COOH (2:1:0.11:0.021, molar ratio), and were conjugated to TF via the carboxyl residue of DSPE-PEG-COOH. The intracellular targeting ability of TF-PEG-liposomes to tumor cells was examined in vitro and in Colon 26 tumor-bearing mice. Results. TF-PEG-liposomes, bearing approximately 25 TF molecules per liposome, readily bound to mouse Colon 26 cells in vitro and were internalized by receptor-mediated endocytosis. TF-PEG-liposomes showed a prolonged residence time in the circulation and low RES uptake in Colon 26 tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue. Electron microscopic studies in Colon 26 tumor-bearing mice revealed that the extravasated TF-PEG-liposomes were internalized into tumor cells by receptor-mediated endocytosis. Conclusion. TF-PEG-liposomes had the capabilities of specific receptor binding and receptor-mediated endocytosis to target cells after extravasation into solid tumors in vivo. Such liposomes should be useful for in vivo cytoplasmic targeting of chemotherapeutic agents or plasmid DNAs to target cells.     

Intracellular Visualization of Ampicillin-Loaded Nanoparticles in Peritoneal Macrophages Infected in Vitro with Salmonella typhimurium

Intracellular targeting of ampicillin by means of polyisohexylcyanoacrylate (PIHCA) nanoparticles was studied in murine peritoneal macrophages infected with Salmonella typhimurium. The intracellular distribution of actively endocytosed nanoparticles was visualized by transmission electron microscopy and confocal microscopy. Nanoparticles were either isolated or closely associated with bacteria within phagosomes or phagolysosomes. Thus the potential of ampicillin-loaded nanoparticles .in targeting of intracellular bacteria is demonstrated. Consequently, ampicillin, which usually penetrates into cells at a low level, is directly carried in, when loaded on nanoparticles, and brought into contact with intracellular bacteria.