Driving delivery vehicles with ultrasound

Therapeutic applications of ultrasound have been considered for over 40 years, with the mild hyperthermia and associated increases in perfusion produced by ultrasound harnessed in many of the earliest treatments. More recently, new mechanisms for ultrasound-based or ultrasound-enhanced therapies have been described, and there is now great momentum and enthusiasm for the clinical translation of these techniques. This dedicated issue of Advanced Drug Delivery Reviews, entitled "Ultrasound for Drug and Gene Delivery," addresses the mechanisms by which ultrasound can enhance local drug and gene delivery and the applications that have been demonstrated at this time. In this commentary, the identified mechanisms, delivery vehicles, applications and current bottlenecks for translation of these techniques are summarized.     

A review on phospholipids and their main applications in drug delivery systems

Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of the species of phospholipids on the efficiency of drug delivery. We refer to some relevant literatures, starting from the structures, main sources and properties of phospholipids to introduce their applications in drug delivery systems. The present article focuses on introducing five types of carriers based on phospholipids, including liposomes, intravenous lipid emulsions, micelles, drug-phospholipids complexes and cochleates.     

脂质体经皮给药系统的研究进展

目的对近年来脂质体经皮给药系统的研究与应用进行文献整理和归纳,为以后该领域的研究提供借鉴意义。方法通过查阅近5年脂质体经皮给药的相关文献,总结脂质体经皮给药的分类、作用机制、影响因素以及新型脂质体的研究进展,提出其在今后研究的重点方向。结果脂质体的经皮使用取得了较大的进步,新型的脂质体相对于普通脂质体,可以根据用药目的进行设计,改变脂质体的变形性、皮肤渗透性、稳定性等,更有利于皮肤用药。结论脂质体经皮给药系统是一种安全、有效的给药途径,其顺应性更好。     

Targeted drug delivery via folate receptors

Targeted delivery via selective cellular markers can potentially increase the efficacy and reduce the toxicity of therapeutic agents. The folate receptor (FR) has two glycosyl phosphatidylinositol (GPI)-anchored isoforms, α and β. FR-α expression is frequently amplified in epithelial cancers, whereas FR-β expression is found in myeloid leukemia and activated macrophages associated with chronic inflammatory diseases. Conjugates of folic acid and anti-FR antibodies can be taken up by cancer cells via receptor-mediated endocytosis, thus providing a mechanism for targeted delivery to FR+ cells. The aim of this article is to provide a brief overview of applications of FR targeting in drug delivery, with an emphasis on the strategy of using folate as a targeting ligand. In order to do this, recent literature is surveyed on targeted delivery via both FR sub-types, as well as new findings on selective receptor upregulation in the targeted cells. A wide variety of molecules and drug carriers, including imaging agents, chemotherapeutic agents, oligonucleotides, proteins, haptens, liposomes, nanoparticles and gene transfer vectors have been conjugated to folate and evaluated for FR-targeted delivery. Substantial targeting efficacy has been found both in vitro and in vivo. In addition, mechanisms and methods for selective FR upregulation have been uncovered, which might enhance the effectiveness of the FR-targeted delivery strategy. FR-α serves as a useful marker for cancer, whereas FR-β serves as a marker for myeloid leukemia and chronic inflammatory diseases. FR-targeted agents have shown promising efficacy in preclinical models and significant potential for future clinical application in a wide range of diseases.     

Trends and developments in liposome drug delivery systems

Since the discovery of liposomes or lipid vesicles derived from self-forming enclosed lipid bilayers upon hydration, liposome drug delivery systems have played a significant role in formulation of potent drugs to improve therapeutics. Currently, most of these liposome formulations are designed to reduce toxicity and to some extent increase accumulation at the target site(s) in a number of clinical applications. The current pharmaceutical preparations of liposome-based therapeutics stem from our understanding of lipid-drug interactions and liposome disposition mechanisms including the inhibition of rapid clearance of liposomes by controlling size, charge, and surface hydration. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes targeted to tissues and cells with or without expression of target recognition molecules on liposome membranes. Enhanced safety and heightened efficacy have been achieved for a wide range of drug classes, including antitumor agents, antivirals, antifungals, antimicrobials, vaccines, and gene therapeutics. Additional refinements of biomembrane sensors and liposome delivery systems that are effective in the presence of other membrane-bound proteins in vivo may permit selective delivery of therapeutic compounds to selected intracellular target areas.     

A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery

Abstract

The pH-sensitive liposomes have been extensively used as an alternative to conventional liposomes in effective intracellular delivery of therapeutics/antigen/DNA/diagnostics to various compartments of the target cell. Such liposomes are destabilized under acidic conditions of the endocytotic pathway as they usually contain pH-sensitive lipid components. Therefore, the encapsulated content is delivered into the intracellular bio-environment through destabilization or its fusion with the endosomal membrane. The therapeutic efficacy of pH-sensitive liposomes enables them as biomaterial with commercial utility especially in cancer treatment. In addition, targeting ligands including antibodies can be anchored on the surface of pH-sensitive liposomes to target specific cell surface receptors/antigen present on tumor cells. These vesicles have also been widely explored for antigen delivery and serve as immunological adjuvant to enhance the immune response to antigens. The present review deals with recent research updates on application of pH-sensitive liposomes in chemotherapy/diagnostics/antigen/gene delivery etc.     

Nanoparticles for human liver-specific drug and gene delivery systems: in vitro and in vivo advances

A wide variety of nanoparticles (NPs) that can deliver incorporated therapeutic materials such as compounds, proteins, genes and siRNAs to the human liver have been developed to treat liver-related diseases. This review describes NP-based drug and gene delivery systems such as liposomes (including lipoplex), polymer micelles, polymers (including polyplex) and viral vectors. It focuses upon the modification of these NPs to enhance liver specificity or delivery efficiency in vitro and in vivo. We discuss recent advances in drug and gene delivery systems specific to the human liver utilizing bio-nanocapsules comprising hepatitis B virus (HBV) envelope L protein, which has a pivotal role in HBV infection. These NP-based medicines may offer novel strategies for the treatment of liver-related diseases and contribute to the development of nanomedicines targeting other tissues.     

Liposomes in Pulmonary Applications: Physicochemical Considerations,Pulmonary Distribution and Antioxidant Delivery

Abstract

The application of liposomes for improved drug delivery to the lung is promising. Liposome-mediated pulmonary drug delivery promotes an increase in drug retention-time in the lung and more importantly, a reduction in extrapulmonary side-effects, invariably resulting in enhanced therapeutic efficacies. The engineering of an effective liposomal drug formulation for inhalation therapy must take into consideration the leakage problem associated with the nebulization process; vesicle stability and release kinetics within the pulmonary milieu; and, the altered pharmacokinetics of the entrapped drug. The delivery of liposome-entrapped antioxidants via the tracheobronchial route has been found to be very useful in increasing the half-times of the administered agents, thus providing a sustained release effect for prolonged drug action. The entrapment in liposomes of a-tocopherol, an extremely insoluble but highly effective antioxidant, has been shown to be very effective in ameliorating oxidant-induced injuries in the lung. The use of bifunctional liposomes containing two antioxidants have been determined to provide excellent resistance to an oxidative challenge and appears to hold promise for improved clinical applications in antioxidant therapy.     

青蒿素及其衍生物纳米制剂在抗肿瘤领域中的研究进展

摘 要青蒿素及其部分衍生物在抗肿瘤方面具有潜在的临床应用价值,但存在水溶性差、半衰期短等缺点,故促使众多学者对其药物制剂进行开发和研究。纳米药物传输系统是一种新型药物递送工具,相比传统的片剂、栓剂、注射剂等,具有稳定性好、靶向释药和联合载药等诸多优点。本文综述了青蒿素类药物的纳米传输载体,包括：纳米粒、脂质体、胶束、纳米微乳和其他纳米载体,概括了青蒿素类药物纳米制剂在肿瘤治疗方面的成果和特点,其中着重介绍青蒿素类药物与转铁蛋白的联合载药递药体系的研究进展。     

Nanocarriers for cancer-targeted drug delivery

Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.     

Archaeosomes: an excellent carrier for drug and cell delivery

Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.     

Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles

With the development of nanomedicine, a mass of nanocarriers have been exploited and utilized for targeted drug delivery, including liposomes, polymers, nanoparticles, viruses, and stem cells. Due to huge surface bearing capacity and flexible genetic engineering property, filamentous bacteriophage and phage-mimetic nanoparticles are attracting more and more attentions. As a rod-like bio-nanofiber without tropism to mammalian cells, filamentous phage can be easily loaded with drugs and directly delivered to the lesion location. In particular, chemical drugs can be conjugated on phage surface by chemical modification, and gene drugs can also be inserted into the genome of phage by recombinant DNA technology. Meanwhile, specific peptides/proteins displayed on the phage surface are able to conjugate with nanoparticles which will endow them specific-targeting and huge drug-loading capacity. Additionally, phage peptides/proteins can directly self-assemble into phage-mimetic nanoparticles which may be applied for self-navigating drug delivery nanovehicles. In this review, we summarize the production of phage particles, the identification of targeting peptides, and the recent applications of filamentous bacteriophages as well as their protein/peptide for targeting drug delivery in vitro and in vivo. The improvement of our understanding of filamentous bacteriophage and phage-mimetic nanoparticles will supply new tools for biotechnological approaches.     

Development and characterization of new nanoscaled ultrasound active lipid dispersions as contrast agents

Ultrasound contrast agents are widely used in clinical diagnosis. In recent years, the use of ultrasound contrast agents as therapeutic agents has gained a lot of attention. Of special interest are ultrasound-enhanced gene delivery in various tissues (e.g. cardiac, vascular, skeletal muscle and tumor tissue), ultrasound-enhanced protein delivery (e.g. insulin delivery) and ultrasound-enhanced delivery of small chemicals (e.g. doxorubicin, vancomycin). Commercially available ultrasound contrast agents such as SonoVue® or Optison® are ranged in a size of 2-8 μm. These micronscaled agents show a good ultrasound contrast enhancement and thus they are used for diagnostic imaging. But they are not suitable for targeted drug delivery to tumor tissues or blood clots because for these applications particles smaller than 700 nm are needed. In the present study, we developed new nanoscaled ultrasound contrast agents with a size between 70 and 300 nm. The lipid formulations show excellent contrast intensities using diagnostic ultrasound of about 1.4 MHz. The negatively charged colloidal dispersions are long-time stable under physiological conditions without loss of ultrasound reflectivity. The adjustable supramolecular organization of the carriers depends on the composition and varies from micellar to liposomal structures. The small size and the circulation stability of these systems make them promising for novel diagnostics and controlled drug release applications.     

Niosomes as a propitious carrier for topical drug delivery

Introduction: Topical delivery is defined as drug targeting to the pathologic sites of skin with the least systemic absorption. Drug localization in this case is a crucial issue. For these purposes vesicular drug delivery systems including niosomes, proniosomes, liposomes and transferosomes have been developed.

Areas covered: This review first highlights the role of niosome in dermatology focusing on localized skin delivery and then reviews the most recent literatures regarding specific applications of niosomal drug delivery systems in clinics.

Expert opinion: Niosomes are becoming popular in the field of topical drug delivery due to their outstanding characteristics like enhancing the penetration of drugs, providing a sustained pattern of drug release, increasing drug stability and ability to carry both hydrophilic and lipophilic drugs.     

壳聚糖包覆脂质体递药系统的研究进展

脂质体在药物传递方面被广泛研究,但因结构稳定性差等因素使其应用受到了限制.壳聚糖是一种阳离子多糖,具有良好的生物相容性、生物降解性以及生物黏附性,并且可经化学改性成为性能更佳的壳聚糖衍生物.近年来,壳聚糖及其衍生物包覆脂质体在载药方面的研究得到了越来越多学者的关注.壳聚糖或其衍生物修饰脂质体,可提高其稳定性、黏附渗透性...     

Advanced delivery of Ciclosporin A: present state and perspective

Ciclosporin A has been used as an immunosuppressor for organ transplantation and other autoimmune disorders for a number of years. Its poor biopharmaceutical characteristics of low solubility and permeability makes the uphill task of designing delivery systems even more challenging for the drug delivery scientist. Works have been performed to investigate administration through various body routes, and have employed approaches that use as emulsions, microspheres, nanoparticles, liposomes, physical and chemical penetration enhancers. Although progress has been made, there is still room for improvement in the application of ciclosporin A, as none of these formulations is ideal.     

Nanostructured lipid carriers system: Recent advances in drug delivery

Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.     

Hyaluronic acid and its derivatives in drug delivery and imaging: Recent advances and challenges

Hyaluronic acid (HA) is a biodegradable, biocompatible, nontoxic, and non-immunogenic glycosaminoglycan used for various biomedical applications. The interaction of HA with the CD44 receptor, whose expression is elevated on the surface of many types of tumor cells, makes this polymer a promising candidate for intracellular delivery of imaging and anticancer agents exploiting a receptor-mediated active targeting strategy. Therefore, HA and its derivatives have been most investigated for the development of several carrier systems intended for cancer diagnosis and therapy. Nonetheless, different and important delivery applications of the polysaccharide have also been described, including gene and peptide/protein drugs delivery. The aim of this review was to provide an overview of the existing recent literature on the use of HA and its derivatives for drug delivery and imaging. Notable attention is given to nanotheranostic systems obtained after conjugation of HA to nanocarriers as quantum dots, carbon nanotubes and graphene. Meanwhile, attention is also paid to some challenging aspects that need to be addressed in order to allow translation of preclinical models based on HA and its derivatives for drug delivery and imaging purposes to clinical testing and further their development.     

Biomedical applications of collagen

Collagen is regarded as one of the most useful biomaterials. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenecity, made collagen the primary resource in medical applications. The main applications of collagen as drug delivery systems are collagen shields in ophthalmology, sponges for burns/wounds, mini-pellets and tablets for protein delivery, gel formulation in combination with liposomes for sustained drug delivery, as controlling material for transdermal delivery, and nanoparticles for gene delivery and basic matrices for cell culture systems. It was also used for tissue engineering including skin replacement, bone substitutes, and artificial blood vessels and valves. This article reviews biomedical applications of collagen including the collagen film, which we have developed as a matrix system for evaluation of tissue calcification and for the embedding of a single cell suspension for tumorigenic study. The advantages and disadvantages of each system are also discussed.     

Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides

Cell-penetrating peptides (CPPs) have been used to overcome the lipophilic barrier of the cellular membranes and deliver large molecules and even small particles inside the cell for their biological actions. CPPs are being used to deliver inside cell a large variety of cargoes such as proteins, DNA, antibodies, contrast (imaging) agents, toxins, and nanoparticular drug carriers including liposomes. In this paper, we have reviewed the delivery of different molecules and particles mediated by TAT, Antp, VP22, and other CPPs as well as potential applications of these delivery systems in different areas of vaccine development, cancer immunotherapy, gene delivery, and cellular imaging.