膜融合脂质体给药系统的研究进展

膜融合脂质体是在传统脂质体基础上引入具有融合特性的病毒而形成的一种新的给药系统，它是介于病毒与非病毒性载体之间的杂合体，本文主要对膜融合脂质体给药系统的构建、特点、药物转运的机制及其作为给药系统的研究作一综述。     

主动靶向脂质体在抗肿瘤治疗中的研究进展

主动靶向脂质体给药系统可使抗肿瘤药物与靶组织结合,将药物可控性地分布于靶组织并持续缓慢释药,在提高药物抗癌效果的同时,降低了其对正常组织的不良反应。本文主要介绍了免疫脂质体、受体介导的脂质体、糖基修饰的脂质体及多肽修饰的脂质体等主动靶向脂质体在抗肿瘤研究中的进展。主动靶向脂质体给药系统将会发展为抗肿瘤药物的理想剂型,具有很好的临床应用前景。     

脂质体经皮给药研究进展

目的介绍脂质体作为经皮给药载体的研究进展。方法查阅国内外文献报道，从脂质体作为经皮给药载体特点、促透机制、影响因素及研究进展等方面进行论述。结果脂质体可促进药物的透皮吸收，加强药物的局部作用，提高局部利用度，降低副作用。结论脂质体在经皮给药系统中应用广泛。     

用于抗肿瘤药物递送的脂质体表面修饰策略

脂质体作为一种传统的药物传递系统,因其在药物及蛋白质、基因、核酸等生物活性物质的高效传递方面的应用而备受研究领域的关注。脂质体给药系统在抗肿瘤药物研究领域经历了常规脂质体、长循环脂质体、配体功能脂质体、刺激响应型脂质体等4个阶段。现结合相关文献,综述了这4种脂质体给药系统常用的表面修饰靶向策略和研究进展,以期为脂质体的进一步研究和基本靶向修饰提供参考。     

包合物脂质体靶向系统在给药中的应用

近年来,包合物和脂质体作为药物的载体被广泛用于药物制剂领域,各自发挥着自身的优势。将环糊精包合物应用于脂质体给药系统——这一新型的药物载体,能够更好地提高靶向给药效果。本文通过概述包合物及脂质体的优势,阐明包合物脂质体这一新型给药系统能提高药物的载药量,增加脂质体的稳定性,对提高药物的吸收和临床疗效等方面具有重要意义,对于靶向给药系统的进一步发展具有新的参考价值。     

脂质体促进药物透皮吸收的研究进展

脂质体透皮吸收给药是一种很有发展前途的给药方式。近年来，为了提高经典脂质体的透皮吸收功能，在此基础上进行了透皮机制、制备材料和方法等研究，从而发挥脂质体作为药物优良载体与促进透皮吸收的完美结合。     

脂质体经皮给药研究进展

目的介绍脂质体作为经皮给药载体的研究进展。方法查阅国内外文献报道,从脂质体作为经皮给药载体特点、促透机制、影响因素及研究进展等方面进行论述。结果脂质体可促进药物的透皮吸收,加强药物的局部作用,提高局部利用度,降低副作用。结论脂质体在经皮给药系统中应用广泛。     

脂质体经皮给药研究进展

目的介绍脂质体作为经皮给药载体的研究进展。方法查阅国内外文献报道,从脂质体作为经皮给药载体特点、促透机制、影响因素及研究进展等方面进行论述。结果脂质体可促进药物的透皮吸收,加强药物的局部作用,提高局部利用度,降低副作用。结论脂质体在经皮给药系统中应用广泛。     

脂质体分析方法新进展

脂质体给药系统可降低药物的毒性，增加药物在靶点的聚集并提高药物的疗效。近代物理学实验技术的发展，使脂质体的质量研究进入分子水平。本文主要就近年来脂质体的定性定量分析方法的最新进展作一综述。     

脂质体的药效学研究

脂质体给药系统在降低药物毒性、增加药物在靶点聚集和提高药物疗效等方面起了重要作用。目前已设计出膜上载有或不载靶识别分子的靶向脂质体,包括抗肿瘤药、抗寄生虫药、抗真菌药、激素、多肽、酶类药物及用于疫苗、基因治疗和免疫诊断的药物。本文就脂质体作为药物载体的药效学及应用方面做一综述。     

Liposomes a vesicular nanocarrier: potential advancements in cancer chemotherapy

The indispensable obligation behind the successful therapy of a disease is to deliver the effective drug/bioactive concentration with sustained release manner at the diseased organs without any exposure to the healthy tissues. Novel drug-delivery systems increase the concentration and persistence of drug at the vicinity of the target site and thereby minimize the undesired side effects of the drug to the normal tissues of body. With advances in nanotechnology, several new drug delivery approaches have become available that may fulfil the requirement of safe and effective drug therapy. Among these techniques, vesicular drug-delivery systems, particularly liposomes, are under rigorous research for their applicability to deliver FDA-approved and newer drugs. Liposomes have been widely investigated as one of the most widely used nanocarriers in cancer therapy and have shown their potential in spatial and temporal release of bioactive agents for the effective treatment of various life-threatening diseases, including cancer. Various targeted and triggered-release approaches of bioactive substances using liposomes further improve the applicability of liposomes in cancer therapeutics. Thus, keeping these points in view, the present review has been focussed on application of liposomes for development of liposome technology and its novel applications for effective cancer therapy.     

脂质体制剂的Ⅰ期临床药代动力学研究进展

目的:回顾新型递药系统脂质体制剂的Ⅰ期临床药代动力学研究现状和研究方法。方法:在国际临床试验注册网站和PubMed数据库中检索有关脂质体制剂Ⅰ期临床药代动力学研究的试验或文献,总结目前研究现状;根据FDA和EMA发布的指导原则,并结合发表最多且较成熟的阿霉素脂质体研究实例,概述主要研究方法和特点。结果和结论:目前多数脂质体制剂仍处于临床前和各期临床试验中,且逐年递增;由于脂质体会改变包裹后药物在体内的药动学和组织分布特点,因此Ⅰ期临床药动学研究至关重要,除进行脂质体制剂和非脂质体制剂的单剂量比较研究或多剂量药动学研究外,还可开展质量平衡研究、组织分布研究、药动学/药效学研究等,分析包裹化或非包裹化的药物及其代谢产物药动学参数,为开展后续临床试验提供药动学信息。     

Enzymatic release of antitumor ether lipids by specific phospholipase A2 activation of liposome-forming prodrugs

An enzymatically activated liposome-based drug-delivery concept involving masked antitumor ether lipids (AELs) has been investigated. This concept takes advantage of the cytotoxic properties of AEL drugs as well as the membrane permeability enhancing properties of these molecules, which can lead to enhanced drug diffusion into cells. Three prodrugs of AELs (proAELs) have been synthesized and four liposome systems, consisting of these proAELs, were investigated for enzymatic degradation by secretory phospholipase A(2) (sPLA(2)), resulting in the release of AELs. The three synthesized proAELs were (R)-1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phosphocholine (1-O-DPPC), (R)-1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phosphoethanolamine poly(ethylene glycol)(350) (1-O-DPPE-PEG(350)), and 1-O-DPPE-PEG(2000) of which 1-O-DPPC was the main liposome component. All three phospholipids were synthesized from the versatile starting material (R)-O-benzyl glycidol. A phosphorylation method, employing methyl dichlorophosphate, was developed and applied in the synthesis of two analogues of (R)-1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phosphoethanolamine poly(ethylene glycol). Differential scanning calorimetry has been used to investigate the phase behavior of the lipid bilayers. A release study, employing calcein encapsulated in non-hydrolyzable 1,2-bis-O-octadecyl-sn-glycero-3-phosphocholine (D-O-SPC) liposomes, showed that proAELs, activated by sPLA(2), perturb membranes because of the detergent-like properties of the released hydrolysis products. A hemolysis investigation was conducted on human red blood cells, and the results demonstrate that proAEL liposomes display a very low hemotoxicity, which has been a major obstacle for using AELs in cancer therapy. The results suggest a possible way of combining a drug-delivery and prodrug concept in a single liposome system. Our investigation of the permeability-enhancing properties of the AEL molecules imply that by encapsulating conventional chemotherapeutic drugs, such as doxorubicin, in liposomes consisting of proAELs, an increased effect of the encapsulated drug might be achievable due to an enhanced transmembrane drug diffusion.     

Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties

Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens in ethanolic liposomes have been reported to enhance allergenicity compared with the allergens in similar vehicles without liposomes. The present report includes data on more sensitization studies using the mouse local lymph node assay with three contact allergens encapsulated in different dermal drug-delivery systems: liposomes, ethosomes, and polycaprolactone particles. The results show that the drug-delivery systems are not sensitizers in themselves. Encapsulating the hydrophilic contact allergen potassium dichromate in all three drug-delivery systems did not affect the sensitizing capacity of potassium dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed for encapsulating isoeugenol in polycaprolactone (1100 ± 406) compared with a formulation in acetone:olive oil (4491 ± 819) and in liposomes (3668 ± 950). Further, the size of DNCB-loaded liposomes did not affect the sensitizing properties. These results suggest that modern dermal drug-delivery systems may in some cases magnify or decrease the sensitizing capacity of the encapsulated contact allergen.     

Trigger release liposome systems: local and remote controlled delivery?

Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.     

Encapsulation of poly(d,l-lactide) microparticles with polyelectrolyte multilayers for antigen delivery

Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.     

A novel and simple type of liposome carrier for recombinant interleukin-2

The strong interaction between recombinant interleukin-2 (IL-2) and liposome was characterized and its possible application to drug-delivery control considered. The liposomes were prepared with egg phosphatidylcholine, distearoyl-phosphatidylglycerol (DSPG), dipalmitoyl-phosphatidylcholine, dipalmitoyl-phosphatidylglycerol or distearoyl-phosphatidylcholine (DSPC). Small and hydrophobic liposomes were selected, which were composed of saturated and long-fatty-acid-chain phospholipids. When the composition and the mixture ratio of IL-2 and the liposomewere optimized, morethan 95% ofthe lyophilized IL-2 (Imunace, 350000 JRU) was adsorbed consistently onto the DSPC-DSPG liposome (molar ratio, 10:1; 25 micromol mL(-1); 30 nm in size). Merely mixing IL-2 lyophilized with liposome suspension is convenient pharmaceutically. After intravenous administration to mice, liposomal IL-2 was eliminated half as slowly from the systemic circulation as free IL-2, with more than 13 and 18 times more IL-2 being delivered to the liver and spleen, respectively. After subcutaneous administration of liposomal IL-2 to mice, the mean residence time of IL-2 in the systemic circulation was 8 times that of free IL-2. These results show that IL-2 consistently adsorbs onto the surface of liposomes after optimization of its composition and mixing ratio. Intravenous and subcutaneous administration to mice demonstrates the gradual release of IL-2. Further trials are warranted using these liposomes.     

生物碱类成分脂质体的制备技术

综述了近3年来的生物碱类成分脂质体常规制备方法(如薄膜法、超声波分散法、逆相蒸发法、主动载药法)以及新型脂质体制备技术(制备技术联合应用于新型脂质体、表面修饰脂质体制备、复合磷脂脂质体制备技术)的研究进展.     

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.     

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis – a critical review

Abstract

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.