电磁波控制热敏磁性脂质体靶向给药

本文从新型靶向给药系统-热敏磁性脂质体靶向给药的几个关键之处出发，介绍了目前热敏磁性脂质体的脂质材料、磁性材料、磁定位和电磁波控释研究状况，分析讨论了电磁波在热敏磁性脂质体的磁靶向和药物控释方面的作用,并提出了测量热敏磁性脂质体的电磁参数和选择合适的电磁波频段用于药物控释的必要性。     

磁性药物载体在抗肿瘤方面的研究进展

通过外加磁场的引导作用,使负载抗癌药物的磁性载体靶向定位于靶区,提高靶组织的药物浓度,有效降低药物对正常组织或细胞的毒副作用及其他不良反应。磁性药物载体还具有靶向性、缓释、控释等优点,已成为了肿瘤靶向治疗常用的新型载体系统。本文综述了磁性药物载体磁性纳米颗粒、磁性脂质体、磁性微球在肿瘤治疗与诊断中的应用进展。     

磁性靶向药物的研究概况

磁性药物指将药物和磁性物质共同包裹于聚合物载体中制成的磁性靶向给药系统(MTDDS),利用外加磁场将药物在体内定向移动和定位集中,在磁场区内释放,从而起到靶区局部浓集作用或靶区截流作用.综述磁性靶向药物的组成及分类.对磁性靶向给药系统现存问题进行总结并对前景进行展望.     

热敏脂质体的研究进展

综述以二棕榈酰磷脂酰胆碱（DPPC）等为主要膜材的常规热敏脂质体以及磁性热敏脂质体、长循环热敏脂质体、多聚物热敏脂质体、热敏免疫脂质体的研究进展。以热敏脂质体为载体包埋化疗药物,可结合热疗的优势和靶向给药的特点,提高治疗靶向性,降低全身毒性,增强抗肿瘤疗效。     

毛菊苣总倍半萜磁性纳米脂质体在小鼠体内组织分布和靶向效果

目的研究毛菊苣总倍半萜有效部位、脂质体和磁性纳米脂质体在小鼠体内的组织分布和靶向效果。方法采用高效液相色谱法,以山莴苣素的含量为评价指标,研究毛菊苣总倍半萜有效部位溶液组、脂质体溶液组和磁性纳米脂质体溶液组(加磁场)在小鼠体内不同组织器官的药物浓度;并以AUC0-12 h、平均滞留时间(MRT)和靶向效率(TE)、相对靶向效率(RTE)、靶向指数(TI)为指标评价不同剂型的靶向作用。结果尾静脉注射给药10 min后,磁性纳米脂质体组在心、肝、脾、肺、肾脏组织中山莴苣素浓度较有效部位组、脂质体组显著提高;在动物的肝部体外施加磁场,磁性纳米脂质体组肝部位的AUC0-12 h明显高于其他部位,MRT明显的延长,差异具有显著性(P0.01);TE仅在肝部有增加,且TI大于10。结论在外加磁场的作用下,毛菊苣总倍半萜磁性纳米脂质体可改变药物在动物体内的分布,延长药物的作用时间,提高药物在肝部位的特异性和靶向性。     

热敏靶向脂质体在肿瘤治疗中的研究进展

介绍热敏靶向脂质体在肿瘤热疗中的应用以及国内外研究的现状，并介绍热敏长循环脂质、磁性热敏脂质体、免疫热敏脂质体和多聚物热敏脂质体等新型热敏靶向脂质体的特点和应用。     

热敏脂质体

目的:综述热敏脂质体的原理和它作为靶向药物载体的应用。方法:论述了脂质体相变的原理和热敏脂质体的研究概况,以及携带化疗药物的热敏脂质体和肿瘤热疗结合后治疗效果的增强作用,指出了热敏脂质体的发展前景。结果:热敏脂质体有良好的热靶向性,在肿瘤治疗方面效果明显。结论:热敏脂质体是新一代热靶向药物载体,有重要的开发价值。     

热敏脂质体

目的:综述热敏脂质体的原理和它作为靶向药物载体的应用。方法:论述了脂质体相变的原理和热敏脂质体的研究概况,以及携带化疗药物的热敏脂质体和肿瘤热疗结合后治疗效果的增强作用,指出了热敏脂质体的发展前景。结果:热敏脂质体有良好的热靶向性,在肿瘤治疗方面效果明显。结论:热敏脂质体是新一代热靶向药物载体,有重要的开发价值。     

甲氨蝶呤热敏磁靶向脂质体的制备和靶向性研究

采用正交设计以37℃和43℃释出的游离药物之比为评价指标优化甲氨蝶呤热敏磁靶向脂质体处方。并测定了小鼠尾静脉注射甲氨蝶呤溶液和甲氨蝶呤脂质体后,全血和肌肉中的药物浓度。结果表明,给予甲氨蝶呤脂质体后再外加磁场并置于43℃环境,脂质体靶向效率Te提高6.8倍,相对摄取量Re提高6.5倍。说明本实验制备的脂质体具有很高的靶向性。     

未来药物制剂发展新技术(下)

靶向释药系统 靶向给药系统是根据生物药剂学设想,利用某种载体聚集于作用部位指向给药,可使药物进入所期望的组织或细胞,它包括药物—载体、药物—抗体共扼物,如以脂质体、微球毫微囊、静脉乳剂和磁性药物作载体的各类靶向制剂。 这是一个理想的包括释放和定向传递的药物治疗系统,它能够达到所有预期目标,即在确定的时程内以预定速率在机体特定部位释放一种或多种药物。目前以应用脂质体技术制备靶向制剂和应用单     

Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery

We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210?nm and ?14?mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12?nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.     

Liposomes as targetable drug carriers

The general problem of targeted drug transport is critically reviewed and three principle components of targeted systems are discussed: the target, the vector molecule, and the carrier. Different systems of drug targeting are briefly described: local drug application, chemical modification of the drug molecule, physical targeting under the action of pH, temperature, or magnetic field. The idea of a vector molecule is discussed and different methods of vector molecule coupling with the drug are reviewed (direct coupling, coupling via spacer group or polymer molecule, etc.). It is shown that the most promising approach seems to be the use of a drug-containing microcontainer with the vector molecule immobilized on its outer surface. Different types of microcontainers are briefly described: microcapsules, cell hosts, and liposomes. The advantages of liposomes as drug containers are shown and the main problems of their use for drug targeting in vitro and in vivo conditions are discussed. One of the most important problems is the problem of vector molecule immobilization on liposome surfaces. The principle four different immobilization methods: adsorbtion, incorporation, covalent binding, and hydrophobic binding. Targeted liposome transport is described in model systems, cell cultures, and experimental animals. It is shown that targeted liposomes may release a drug via diffusion, lysis, or endocytosis by appropriate cells. The problems of targeted liposome technology and clinical application are analyzed.     

Preparation and Characterization of Dextran Magnetite-Incorporated Thermosensitive Liposomes: An on-line Flow System for Quantifying Magnetic Responsiveness

Purpose. Dextran magnetite (DM)-incorporated thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs), were prepared and characterized in order to investigate their possibility for magnetic drug targeting. Methods. TMs containing calcein were prepared at various DM concentrations by reverse-phase evaporation of dipalmitoylphosphatidylcholine (DPPC). They were evaluated for their physicochemical properties including size, DM capture, magnetite distribution within liposomes, and temperature-dependent calcein release. Moreover, a novel on-line flow apparatus with a sample injector, a coil of tubing placed in an electromagnet, and a fluorescence detector was developed for quantifying the magnetic responsiveness of TMs. This device allowed us a real-time measurement of percentage holding of TMs by magnetic field. Results. Due to water-soluble property of DM, higher contents of magnetite up to 490 mg per mmol DPPC were successfully incorporated into the liposomes with DM than with conventional magnetite (Fe₃O₄). Thermosensitivity and lipid integrity of TMs were not influenced by inclusion of DM. Using the on-line flow system, percentage holding of TMs by magnetic field was shown to vary with several factors; it increases as the magnetic field strength increases, the fluid flow rate decreases, the magnetite content increases, and the liposome concentration increases. Typically, at 490 mg incorporated magnetite per mmol DPPC, 0.5 ml/min-fluid flow rate, and high magnetic field strength (10 kiloGauss), approximately 100% of TMs were found to be held. Conclusions. The TMs were suggested to be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia.     

Liposome technology for cardiovascular disease treatment and diagnosis

INTRODUCTION: Over the past several decades, liposomes have been used in a variety of applications, from delivery vehicles to cell membrane models. In terms of pharmaceutical use, they can offer control over the release of active agents encapsulated into their lipid bilayer or aqueous core, while providing protection from degradation in the body. In addition, liposomes are versatile carriers, because targeting moieties can be conjugated on the surface to enhance delivery efficiency. It is for these reasons that liposomes have been applied as carriers for a multitude of drugs and genetic material, and as contrast agents, aimed to treat and diagnose cardiovascular diseases. AREAS COVERED: This review details advancements in liposome technology used in the field of cardiovascular medicine. In particular, the application of liposomes to cardiovascular disease treatment and diagnosis, with a focus on delivering drugs, genetic material and improving cardiovascular imaging, will be explored. Advances in targeting liposomes to the vasculature will also be detailed. EXPERT OPINION: Liposomes may provide the means to deliver drugs and other pharmaceutical agents for cardiovascular applications; however, there is still a vast amount of research and clinical trials that must be performed before a formulation is brought to market. Advancements in targeting abilities within the body, as well as the introduction of theranostic liposomes, capable of both delivering treating and imaging cardiac diseases, may be expected in the future of this burgeoning field.     

Nano-sized cationic polymeric magnetic liposomes significantly improves drug delivery to the brain in rats

In recent years, cationic polymeric magnetic liposomes have shown greater stability and prolonged circulation half-life over traditional liposomes. Here, we examined the capability of cationic polymeric magnetic liposomes in delivering drugs into the brain under magnetic targeting with paclitaxel as the loaded agent. We found that the fabricated paclitaxel-loaded magnetic liposomes had a uniform diameter of 20?nm and were superparamagnetic. After they were injected into rats by the caudal vein, brain paclitaxel concentration increased 2–5 folds without magnetic targeting and 5–15 folds after magnetic targeting. The high brain concentration was maintained for more than 8?h, which was significantly longer than that for pure paclitaxel injection. When the liposomes were given via the internal carotid artery at 10% of the dose given via the caudal vein, paclitaxel in the brain was increased by 1.5 folds, indicating that intra-arterial administration enhanced delivery efficiency remarkably. Prussian blue staining of the cortex showed that the magnetic liposomes were aggregated in the cortex vasculature and the cortex cells were under magnetic targeting, indicating that the drugs were delivered across the nearly impermeable blood-brain barrier. These results showed that the nano-sized cationic polymeric magnetic liposomes are potential tools for magnetic drug delivery to the brain.     

Nano-sized cationic polymeric magnetic liposomes significantly improves drug delivery to the brain in rats

In recent years, cationic polymeric magnetic liposomes have shown greater stability and prolonged circulation half-life over traditional liposomes. Here, we examined the capability of cationic polymeric magnetic liposomes in delivering drugs into the brain under magnetic targeting with paclitaxel as the loaded agent. We found that the fabricated paclitaxel-loaded magnetic liposomes had a uniform diameter of 20?nm and were superparamagnetic. After they were injected into rats by the caudal vein, brain paclitaxel concentration increased 2-5 folds without magnetic targeting and 5-15 folds after magnetic targeting. The high brain concentration was maintained for more than 8?h, which was significantly longer than that for pure paclitaxel injection. When the liposomes were given via the internal carotid artery at 10% of the dose given via the caudal vein, paclitaxel in the brain was increased by 1.5 folds, indicating that intra-arterial administration enhanced delivery efficiency remarkably. Prussian blue staining of the cortex showed that the magnetic liposomes were aggregated in the cortex vasculature and the cortex cells were under magnetic targeting, indicating that the drugs were delivered across the nearly impermeable blood-brain barrier. These results showed that the nano-sized cationic polymeric magnetic liposomes are potential tools for magnetic drug delivery to the brain.     

肺靶向吡非尼酮脂质体的制备及体外释药性质研究

目的：研究肺靶向吡非尼酮脂质体的制备方法并考察其体外释药性质。方法：采用薄膜分散法制备吡非尼酮脂质体;用D-甘露糖修饰脂质体并添加适量十八胺调节脂质体表面电荷;用紫外分光光度法测定包封率;用正交实验优化处方,用透析法考察药物体外释放性质。结果：制得的脂质体平均粒径为581.1nm,表面电荷为-20.61mV,包封率为81.1%,稳定性好。药物体外释药符合Weibull方程。结论：采用薄膜分散法,用D-甘露糖修饰并添加十八胺可制得具有较高包封率及稳定性的吡非尼酮脂质体,有助于提高吡非尼酮的肺靶向性。     

Thermosensitive magnetic liposomes with doxorubicin cell-penetrating peptides conjugate for enhanced and targeted cancer therapy

To specifically deliver cytotoxic drug to tumor cells and enhance cellular uptake is the key for effective cancer therapy. In this paper, we described a novel drug targeting system, which is designed to combine features of biological (cell-penetrating peptides, CPPs) and physical (magnetic) drug targeting for use in the magnetic hyperthermia-triggered release. A doxorubicin–CPPs conjugate (DOX-CPPs) was loaded into thermosensitive magnetic liposomes (TSMLs) (DOX-CPPs/TSMLs), and in vitro DOX-CPPs thermosensitive release activity, anti-proliferation effect, in vivo targeted delivery as well as in vivo antitumor activity were determined. The results demonstrated that the DOX-CPPs/TSMLs showed good physicochemical properties, effective anti-proliferation effect in MCF-7 cells in vitro. Additionally, in vivo study, DOX-CPPs/TSMLs under AC magnetic field displayed superior in vivo targeted delivery efficacy, antitumor efficacy in an MCF-7 xenograft murine model. In conclusion, the application of DOX-CPPs/TSMLs under AC magnetic field may provide a strategy for the selective and efficient delivery of drug.     

Synergic fabrication of multifunctional liposomes nanocomposites for improved radiofrequency ablation combination for liver metastasis cancer therapy

The field of biomedical research has recently been interested in nanoplatforms with various functionalities, such as cancer drug carriers and MRI and optical imaging, as well as thermal treatment, among other things. As a result of the present investigation, a unique multifunctional liposome (MFL) was established in this investigation. Using radiofrequency-induced imaging and drug release based on magnetic field impact, a dual drug delivery targeted with tumor multi-mechanism treatment was made more effective. The C60 (fullerene) surface was coated with iron nanocomposites to establish the proposed nanosystems, and PEGylation was used (Fe₃O₄-C60-PEG₂₀₀₀). For fullerene radiofrequency-triggered drug release, thermosensitive DPPC liposomes with folate-DSPE-PEG₂₀₀₀ enveloped the binary nanosystems and doxorubicin (DOX). The in vitro cytotoxicity of the nanocomposites was confirmed by the liver metastasis in HT-29 colon cancer cells using radiofrequency. The flow cytometry analysis confirmed the apoptosis cell death mechanism. The thermal treatment combined chemotherapeutic MFL nano framework transformed radiofrequency radiation from thermoresponsive liposomes, which was noticed both in vivo and in vitro. Due to their superior active tumor targeting and magnetic targeting characteristics, the MFL could also selectively destroy cancerous liver cells in highly co-localized targets.