疏血通+单硝酸异山梨酯治疗老年无症状心肌缺血的临床效果评价

目的研究老年无症状心肌缺血疾病患者采用单硝酸异山梨酯联合疏血通进行治疗的临床效果。方法选择以往在我院接受治疗的106例老年无症状心肌缺血疾病患者,分成对照组和治疗组,平均每组53例。对照组采用单硝酸异山梨酯进行治疗;治疗组采用单硝酸异山梨酯联合疏血通进行治疗。结果治疗组患者在用药后动态心电图表现恢复正常时间和用药总时间短于对照组(P <0.05);药物导致的不良反应仅有3例,少于对照组的11例(P <0.05);心肌缺血病情控制总有效率为90.6%,对照组为64.2%(P <0.05)。结论老年无症状心肌缺血疾病患者采用单硝酸异山梨酯联合疏血通进行治疗,可以有效减少药物导致的不良反应,缩短用药时间,提高治疗效果。     

单硝酸异山梨酯有关物质的测定

单硝酸异山梨酯 (5 -ＩＳＭＮ)为新一代硝酸异山梨酯类抗心绞痛药 ,吸收良好 ,半衰期长。 80年代首先在西德上市 ,国内已有多种剂型批准生产 ,对其含量测定报道很多 ,但对原料及其制剂的有关物质测定未见系统报道 ,本文参考有关文献 ,结合单硝酸异山梨酯的生产工艺及性质 ,采用ＨＰＬＣ和ＴＬＣ两种方法对其主要有关物质 2 -单硝酸异山梨酯 (2 -ＩＳＭＮ)和硝酸异山梨酯 (ＩＳＤＮ)进行了检测 ,结果表明两种方法分离和检测效果都很好 ,ＨＰＬＣ法的灵敏度、分离度、重现性有更大优势 ,且能够控制样品杂质的量。1　试药和仪器单硝酸异山梨酯…     

RP-HPLC法检查单硝酸异山梨酯片的有关物质

目的:建立单硝酸异山梨酯片有关物质检查方法.方法:采用反相高效液相色谱法.色谱条件为:ODS柱,以甲醇-水(25:75)为流动相,检测波长为210 nm.结果:该色谱条件可有效分离单硝酸异山梨酯、2-单硝酸异山梨酯、硝酸异山梨酯及破坏性试验产物.结论:根据原料合成工艺、制剂破坏性试验,建议在单硝酸异山梨酯片有关物质检查中增加其他杂质的考察.     

让合理、安全用药知识(五十二) 走进千家万户

(接上期)四、抗心绞痛药2.单硝酸异山梨酯(5-单硝酸异山梨醇、5-单硝酸异山梨醇酯、5-单硝酸异山梨酯、长效心痛治、异乐定)新一代长效硝酸酯类抗心绞痛药,作用机制与硝酸甘油相同,但作用时间较长。临床用于:1.用于冠心病的长期治疗;预防劳累性心绞痛、变异型心绞痛及混合     

单硝酸异山梨酯缓释片对慢性高原病大鼠模型睾丸的保护作用

目的研究单硝酸异山梨酯缓释片对慢性高原病(CMS)大鼠模型睾丸的保护作用。方法建立CMS模型,随机分为正常对照组、高原模型组、阳性对照组和单硝酸异山梨酯缓释片低、中、高剂量组。观察其肺动脉压(PAP)和睾丸组织病理学的变化,测定白介素-6(IL-6)、C-反应蛋白(CRP)、超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽-过氧化氢酶(GSH-PX)等指标。结果与正常对照组比较,高原模型组、阳性对照组和单硝酸异山梨酯缓释片各剂量组大鼠体内的PAP、IL-6、CRP和MDA水平升高,SOD和GSH-PX水平降低,光镜下可见大鼠睾丸组织受到损伤,提示低氧对大鼠的睾丸造成损害。与高原模型组比较,单硝酸异山梨酯缓释片高剂量组大鼠体内的PAP、IL-6、CRP和MDA水平降低,SOD和GSH-PX水平升高,均接近正常值,且优于阳性对照组。同时,睾丸组织病理切片亦出现相应改善。结论高剂量的单硝酸异山梨酯缓释片对CMS大鼠模型睾丸有保护作用。     

让合理、安全用药知识(五十二) 走进千家万户

正(接上期)四、抗心绞痛药2.单硝酸异山梨酯(5-单硝酸异山梨醇、5-单硝酸异山梨醇酯、5-单硝酸异山梨酯、长效心痛治、异乐定)新一代长效硝酸酯类抗心绞痛药,作用机制与硝酸甘油相同,但作用时间较长。临床用于:1.用于冠心病的长期治疗;预防劳累性心绞痛、变异型心绞痛及混合     

通心络与单硝酸异山梨酯合用治疗老年冠心病心绞痛60例疗效观察

目的探讨通心络与单硝酸异山梨酯合用治疗冠心病心绞痛的临床疗效。方法以临床症状、体表心电图、血脂分析等方法观察通心络与单硝酸异山梨酯合用治疗老年冠心病心绞痛的疗效,并与单用单硝酸异山梨酯组作对照。结果通心络与单硝酸异山梨酯合用临床症状有效率96.67%、心电图改善76.67%、显效率均高于单用单硝酸异山梨酯组(P<0.05);血清胆固醇和低密度脂蛋白治疗后下降明显(P<0.05),而单用单硝酸异山梨酯组治疗前后血脂无明显变化(P>0.05)。结论通心络与单硝酸异山梨酯合用能够很好地改善老年冠心病心绞痛的临床症状及心电图的缺血变化,并对血液黏稠度和血脂有很好的改善作用,同时能减少单硝酸异山梨酯的用量及副作用。     

通心络与单硝酸异山梨酯合用治疗老年冠心病心绞痛疗效观察

目的 :探讨通心络与单硝酸异山梨酯合用治疗冠心病心绞痛的临床疗效。方法 :以临床症状、体表心电图、血脂分析等方法观察通心络与单硝酸异山梨酯合用治疗老年冠心病心绞痛的疗效 ,并与单用单硝酸异山梨酯组作对照。结果 :通心络与单硝酸异山梨酯合用临床症状有效率 96 .6 7%、心电图改善 76 .6 7%、显效率均高于单用单硝酸异山梨酯组 (P <0 .0 5 ) ;血清胆固醇和低密度脂蛋白治疗后下降明显 (P <0 .0 5 ) ,而单用单硝酸异山梨酯组治疗前后血脂无明显变化 (P >0 .0 5 )。结论 :通心络与单硝酸异山梨酯合用能够很好地改善老年冠心病心绞痛的临床症状及心电图的缺血变化 ,并对血液黏稠度和血脂有很好的改善作用 ,同时能减少单硝酸异山梨酯的用量及副作用     

单硝酸异山梨酯治疗30例缺血性心肌病的观察

目的 观察单硝酸异山梨酯治疗缺血性心肌病患者的疗效及价值.方法 将60例缺血型心肌病患者分为单硝酸异山酯组与对照组给予常规抗心力衰竭治疗,单硝酸异山梨组是在常规治疗组的基础上加服单硝酸异山梨酯,治疗后监测心脏彩超、临床心功能.结果 单硝酸异山梨酯组患者治疗后LVDD(左室舒张末内径)、LVEF(左室射血分数)、FS(左室缩短率)治疗前后比较差异有统计学意义,且LVEF、FS与对照组比较差异有统计学意义,单硝酸异山梨酯组有效率高于对照组.结论 单硝酸异山无酯对缺血型心肌病有确切疗效.     

高原低氧对大鼠血管内皮细胞NO生成的影响

目的观察NO供体药单硝酸异山梨酯和NO合酶(NOS)抑制剂L-NAME对SD大鼠(平原组)与SD大鼠(高原组)的不同作用,探讨高原低氧对血管内皮细胞NO生成的影响。方法SD大鼠灌胃单硝酸异山梨酯,用SD大鼠腹腔注射L-NAME阻断NO生成,测SD大鼠血压和SOD值。结果高原组较平原组大鼠血压升高,SOD值存在不同。结论高原低氧环境下SD大鼠NO合成减少,可能是存在NO通路多个环节的障碍——底物的减少、NOS活性的降低和血管平滑肌细胞对NO不敏感等。     

载阿霉素透明质酸聚合物纳米粒的构建及其体外性质研究

目的 合成透明质酸（HA）接枝单油酸甘油酯（GMO）两亲性聚合物HGO,并研究其所制备载阿霉素（DOX）纳米粒的理化性质及体外抗肿瘤效果。方法 HA与GMO通过酯化反应制得载体聚合物HGO,通过核磁共振波谱法及红外光谱法对其进行结构表征;采用芘荧光探针法测定聚合物临界聚集浓度（CAC）。采用透析法制备聚合物HGO载阿霉素（DOX@HGO）纳米粒,并对其进行粒径分布、Zeta电位及微观形态的表征;通过检测其在不同离子强度、不同pH条件下的粒径变化考察纳米粒的体外稳定性;考察DOX@HGO纳米粒在不同pH条件下的体外释放行为;CCK-8法考察DOX@HGO纳米粒对MDA-MB-231细胞的体外抑瘤效果;并通过荧光显微镜研究MDA-MB-231细胞对DOX溶液、DOX@HGO纳米粒的摄取能力,以及HA预处理对DOX@HGO纳米粒摄取的影响。结果 成功制得两亲性聚合物HGO,聚合物HGO中GMO的取代度为15.8%,CAC为0.023 mg·mL^-1。DOX@HGO纳米粒呈规则的球形,平均粒径为（130.800±1.709）nm,平均电位为（-32.600±0.153）mV,包封率和载药量分别为（98.65±0.74）%和（33.03±0.17）%,在不同离子强度下、模拟胃肠液中表现出良好的稳定性;DOX@HGO纳米粒的体外释放表现出pH依赖性。体外抗肿瘤活性实验表明,DOX@HGO纳米粒对MDA-MB-231细胞的生长具有较好的抑制作用;与DOX溶液比较,DOX@HGO纳米粒显著增加肿瘤细胞对于DOX的摄取（P＜0.05） ,HA预处理显著减少肿瘤细胞对DOX@HGO的摄取（P＜0.05）。结论 所构建的DOX@HGO纳米粒具有良好的理化性质,并且具有一定的pH敏感性及靶向抗肿瘤细胞的能力,是具有应用潜力的药物载体。     

冰片和叶酸共修饰的阿霉素聚酰胺-胺复合物在动物体内的研究

目的 研究用冰片（borneol,BO）和叶酸（folic acid,FA）共修饰阿霉素（doxorubicin,DOX）聚酰胺-胺型树状[poly（amido amine）,PAMAM]大分子（FA-BO-PAMAM/DOX）,增加药物在脑胶质瘤部位递送。方法 第5代PAMAM树状大分子分别与BO和FA通过共价结合得FA-BO-PAMAM。以FA-BO-PAMAM为纳米载体,制备了FA-BO-PAMAM/DOX,通过尾静脉注射该复合物,考察荷瘤大鼠体内的药动学行为及组织分布情况。结果 BO-PAMAM/DOX和FA-BO-PAMAM/DOX组的大鼠血浆半衰期（plasma half-life,t_1/2）和平均滞留时间（mean retention time,MRT）均较原药组显著延长（P<0.01）;血药浓度-时间曲线下面积（area under the plasma concentration-time curve,AUC）较原药组显著增大（P<0.01）。与DOX相比,BO-PAMAM/DOX和FA-BO-PAMAM/DOX在肿瘤组织中的药物含量明显增加,而在心脏中的药物含量明显降低。结论 采用合成的药物载体FA-BO-PAMAM包载DOX后,可显著改变DOX的部分药动学参数,使药物在血浆中能维持较长时间。另外FA-BO-PAMAM/DOX具有较好的肿瘤靶向治疗效果和较小的心脏不良反应,对提高DOX的治疗指数具有较好的临床价值。     

Which one performs better for targeted lung cancer combination therapy: pre- or post-bombesin-decorated nanostructured lipid carriers?

Abstract

Purpose: The co-delivery of gene and drugs has the potential to treat cancer. The aim of this study was to compare post-bombesin decorated nanostructured lipid carriers (NLC) carrying both doxorubicin (DOX) and DNA with pre-bombesin decorated NLC for lung cancer therapy.

Methods: Post-bombesin decorated NLC were prepared by two steps. First, DOX and DNA-loaded NLC (DOX-DNA-NLC) was prepared. Second, Bombesin-NH₂ (BN-NH₂) was added into DOX-DNA-NLC to react with stearic acid-polyethylene glycol-COOH (SA-PEG-COOH) loaded in NLC. Pre-bombesin decorated NLC were prepared by two steps. First, Bombesin (BN)-conjugated ligands were synthesized. Second, DOX and DNA were loaded into BN decorated NLC. Their average size, zeta potential, drug and gene loading were evaluated. NCl-H460 human non-small lung cancer cells (NCl-H460 cells) were used for the testing of in vitro transfection efficiency and in vitro cytotoxicity. In vivo transfection efficiency and anti-tumor effect of NLC were evaluated on mice bearing NCl-H460 cells model.

Results: Post-bombesin decorated NLC has a particle size of 128?nm, DOX encapsulation efficiency (EE) of 85% and DNA EE of 91%. Pre-bombesin decorated NLC has a particle size of 101?nm, DOX EE of 86% and DNA EE of 92%. Post-bombesin decorated NLC displayed more stable and remarkably higher transfection efficiency and better anti-tumor ability than pre-bombesin decorated NLC both in vitro and in vivo.

Conclusion: Post-bombesin decorated NLC could function as better carriers to improve the cell targeting and nuclear targeting ability. The resulting nanomedicine could be a promising active targeting drug/gene therapeutic system for lung cancer therapy.     

Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy

Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H₂O₂ and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe³⁺, trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe³⁺could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe²⁺generation. Second, the cleavage of trisulfide bond could also consume GSH, and the released DOX induces the generation of H₂O_2, which would react with the generated Fe²⁺in step one to induce efficient Fenton reaction-dependent ferroptosis. Third, the formed Fe³⁺/Fe²⁺ couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis. This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion, ROS generation and lipid peroxidation, providing new sights for efficient cancer therapy.     

pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy

Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NH₄HCO₃; abc) and chemotherapeutic agent doxorubicin (DOX) were loaded into the pores of mesoporous silica. Indocyanine green (ICG) as a photothermal and photodynamic agent was loaded onto the polydopamine (PDA) layer surface. The synthesized nanoparticles displayed a narrow polydispersity (PDI) and small particle size as characterized through dynamic light scattering-autosizer analysis. The nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal studies. DOX release analysis confirmed that the nanoparticles were pH-dependent and that NH₄HCO₃ accelerated drug release. At the same time, the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth remarkably. In summary, the multifunctional nanoparticles presented a promising system for combination therapy.Key words: Mesoporous silica, pH-sensitive, Bubble-generating, Targeting modification, Combination therapy     

Formation of graphene oxide-hybridized nanogels for combinative anticancer therapy

The low efficacy and high toxicity of chemotherapy have been driving increasing attention on development of combined anticancer therapy technique. In the current work, graphene oxide (GO)-hybridized nanogels (AGD) were developed for delivery of an anticancer drug (doxorubicin (DOX)), which simultaneously presented photothermal therapeutic effects against cancer cells. AGD nanogels were fabricated by in situ incorporating GO nanoplatelets into a biodegradable polymer (alginate) via a double emulsion approach using a disulfide molecule as crosslinker, followed by DOX encapsulation via electrostatic interactions. The nanogels released DOX drug in an accelerated way under both acidic and reducible conditions mimicking extracellular tumor microenvironments and intracellular compartments. The stimulative release controllability of the nanogels improved the DOX internalization and long-term drug accumulation inside A549 cells (an adenocarcinoma human alveolar basal epithelial cell line), which, together with their photothermal effect, resulted in a good anticancer cytotoxicity, indicating their promising potential for combinative anticancer therapy.     

Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe₃O₄@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe₃O₄@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe₃O₄@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T₂ magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe₃O₄@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.     

A Multi-Functional Tumor Theranostic Nanoplatform for MRI Guided Photothermal-Chemotherapy

Purpose

To develop a multi-functional theranostic nanoplatform with increased tumor retention, improving antitumor efficacy and decreased side effects of chemotherapy drugs.

Methods

GO@Gd nanocomposites was synthesized via decorating gadolinium (Gd) nanoparticles (GdNP) onto graphene oxide (GO), and then functionalized by polyethylene glycol (PEG2000), folic acid (FA), a widely used tumor targeting molecule, was linked to GO@Gd-PEG, finally, doxorubicin (DOX) was loaded onto GO@Gd-PEG-FA and obtained a tumor-targeting drug delivery system (GO@Gd-PEG-FA/DOX). GO@Gd-PEG-FA/DOX was characterized and explored its theranostic applications both in a cultured MCF-7 cells and tumor-bearing mice.

Results

GO@Gd-PEG-FA/DOX could efficiently cross the cell membranes, lead to more apoptosis and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 7.6-fold higher DOX uptake of tumor than DOX. Besides, GO@Gd-PEG-FA/DOX also served as a powerful photothermal therapy (PTT) agent for thermal ablation of tumor and a strong T1-weighted contrast agent for tumor MRI diagnosis. The multi-functional nanoplatform also could selectively kill cancer cells in highly localized regions via the excellent tumor-targeting and MRI guided PTT abilities.

Conclusions

GO@Gd-PEG-FA/DOX exhibited excellent photothermal-chemotherapeutic efficacy, tumor-targeting property and tumor diagnostic ability.

     

Combination prostate cancer therapy: Prostate-specific membranes antigen targeted,pH-sensitive nanoparticles loaded with doxorubicin and tanshinone

Prostate cancer is the second most frequently diagnosed cancer in the men population. Combination anticancer therapy using doxorubicin (DOX) and another extract of traditional Chinese medicine is one nano-sized drug delivery system promising to generate synergistic anticancer effects, maximize the treatment effect, and overcome multi-drug resistance. The purpose of this study is to construct a drug delivery system for the co-delivery of DOX and tanshinones (TAN). Lipid nanoparticles loaded with DOX and TAN (N-DOX/TAN) were prepared by emulsification and solvent-diffusion method. PSMA targeted nanoparticles loaded with DOX and TAN (P-N-DOX/TAN) were synthesized by conjugating a PSMA targeted ligand to N-DOX/TAN. We evaluate the performance of this system in vitro and in vivo. P-N-DOX/TAN has a size of 139.7 ± 4.1 nm and a zeta potential of 11.2 ± 1.6 mV. The drug release of DOX and TAN from P-N-DOX/TAN was much faster than that of N-DOX/TAN. N-DOX/TAN presented more inhibition effect on tumor growth than N-DOX and N-TAN, which is consistent with the synergistic results and successfully highlighting the advantages of combing the DOX and TAN in one system. P-N-DOX/TAN achieved higher uptake by LNCaP cells (58.9 ± 1.9%), highest tumor tissue distribution, and the most significant tumor inhibition efficiency. The novel nanomedicine offers great promise for the dual drug delivery to prostate cancer cells, showing the potential of synergistic combination therapy for prostate cancer.     

PEGylated FePt@Fe2O3 core-shell magnetic nanoparticles: Potential theranostic applications and in vivo toxicity studies

Herein, we develop FePt@Fe₂O₃ core-shell magnetic nanoparticles as a T₂ magnetic resonance (MR) imaging contrast agent as well as a drug carrier for potential cancer theranostic applications. The FePt@Fe₂O₃ core-shell nanoparticles are synthesized and then functionalized with polyethylene glycol (PEG). Folic acid (FA) is conjugated on the surface of FePt@Fe₂O₃-PEG nanoparticles for effective targeting of folate receptor (FR)-positive tumor cells. A chemotherapy drug, doxorubicin (DOX), is then loaded onto those nanoparticles via hydrophobic physical adsorption, for targeted intracellular drug delivery and selective cancer cell killing. We then use those FePt@Fe₂O₃-PEG nanoparticles for in vivo MR imaging, observing obvious tumor MR contrasts, which resulted from both passive tumor accumulation and active tumor targeting of nanoparticles. Moreover, both in vitro and in vivo studies uncover no obvious toxicity for FePt@Fe₂O₃-PEG nanoparticles. Therefore, our PEGylated FePt@Fe₂O₃ core-shell nanoparticles could serve as a promising multifunctional theranostic nano-platform in imaging guided cancer therapy.From the Clinical EditorIn this study of PEGylated FePt@Fe₂O₃ core-shell magnetic nanoparticles, both therapeutic and diagnostic applications are demonstrated. Folic acid surface-conjugation resulted in uptake by folate receptor positive cancer cells, the iron oxide particles enabled MRI imaging using T2* weighted sequences, and the absorbed doxorubicin provided treatment effects in this model. Similar multi-modality approaches will hopefully find their way to clinical applications in the near future.