Particle dosage forms have been receiving much attention in drug delivery systems because of such features as controlled release, absorption improvement and drug targeting. In addition, unlike polymer drugs and prodrugs, particles have the advantage of ability to carry many drug molecules. Most particle formulations have been designed to reduce toxicity and to increase accumulation at target sites, to some extent being used for in a number of clinical applications. Especially lipid-based particles such as liposomes, emulsions and solid particles composed of lipids (solid lipid particles, SLN) have been focused on use for drug delivery systems. Currently, Lipid-based particles are mostly used for controlled release of drugs, whereas cationic liposomes and emulsions are used as vectors for gene delivery. The introduction of polyetyleneglycol derivative (PEG) to lipids, i. e. “PEGlated” as long-circulating liposomes and the “remote loading” method for drug loading into the liposomes has produced liposome-encapsulated drugs for chemotherapy. PEGlated technique has also been applied to injectable microemulsions and solid lipid particles. The area of liposome targeting, e. g. use of antibody-targeting liposomes, has been extensively studied. In gene delivery, the role of helper lipids such as cholesterol and DOPE as well as that of PEG lipids in cationic liposomes in improving transfection efficiency in vivo has been reported. The study of drug distribution in particles, and design of particles targeted at tissues and cells with ligands and biosenser induced to nucleus are needed for the clinical use of lipid-based particles.

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To develop microparticulate drug delivery system, numerous approaches have been tried to optimize the drug delivery. In this review, functional design of microparticlate drug delivery systems by controlling the particle size are focused. The particle size affect biodistribution after i. v. administration, drug release rate, bioavailability through the mucus layer via oral, nasal and pulmonary administration, Among the characteristic functions of nano-and micro-spheres, the ability to deliver the drug across a number of biological barriers to the target site is attractive for drug carriers. The mucosal delivery of high molecular weight substances, such as peptides, proteins, oligonucleotides and plasmids using nanoparticulate systems are discussed in the view of challenges for drug and gene targeting. Lymphatic targeting of drugs has been achieved with nanospheres with a suitable size distribution and appropriate surface characteristics to enhance the accumulation of drug in the lymph nodes following oral administration, In addition to the intestinal mucosal transportation of particles, the particle transfer across nasal and pulmonary mucosa is also discussed.

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More than 2 years have passed since Levovist^®, a clinically applicable contrast agent for image diagnosis by intravenous ultrasonography, was approved. After start of the clinical use, there were advances in the ultrasonographic apparatuses, and as a result of positive efforts for clinical application, the usefulness of this compound was recognized in such areas as differential diagnosis of tumorous lesions by evaluation of blood flow pattern mainly in the liver especially in the abdominal field ; and evaluation of effectiveness in the localized treatment of hepatocellular carcinoma ; and its usefulness as a guide for additional treatment was also recognized. At the same time, a study was conducted on the interaction between micro-bubble and exposure to ultrasound, and a possibility of its use in DDS was suggested. In this paper, we summarized the background leading to the development of this contrast agent for ultrasonography, and future possibilities of this compound was also discussed.

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Plasma lipoproteins are endogenous colloidal particles that transport lipid through the blood to various cells, where they are recognized and taken up via specific receptors. It is known that plasma lipoprotein binding of some hydrophobic drugs can significantly influence not only the pharmacological and pharmacokinetic properties of the drug, but the relative toxicity as well. Many lipid particulate systems, such as lipid emulsions and liposomes, are under investigation as a potential vehicle for drug delivery. Plasma lipoprotein particles are also recognized as excellent candidates for the targeted delivery of drugs to various cells such as hepatic parenchymal cells, malignant cells, and atherosclerotic cells. Recent studies showed that not only these synthesized recombinant lipoproteins but also lipid emulsions from many kinds of lipids are closely mimic the metabolic fate of endogenous plasma lipoproteins. This means that the composition and physicochemical nature of the lipid particles for drug delivery can control the drug disposition in the body in accordance with a way of the lipoprotein metabolism. Like native lipoproteins, these particles are biodegradable, do not seem to trigger immune reactions, and are not recognized by the RES. This review article will overview the researches in the areas of lipoprotein-drug interactions and development of recombinant lipoproteins and lipid emulsion formulations for site-specific drug delivery in relation to lipoprotein metabolism.

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Liposomes are the models of membranes. Liposomalization of various drugs has revealed the enhancement of their efficacy : Since liposomes can reduce the side effect of the drugs by the site-specific delivery, intracellular targeting, and controlled release of drugs, many functional liposomes have been developed including cationic liposomes and antibody-conjugating immunoliposomes. In this article, the preparation and characterization of functional liposomes are discussed. We have developed intracellular hyperthermia using magnetic nanoparticles (magnetites) by the feature that magnetites can generate heat under high frequency alternative magnetic field. In addition, magnetites affect the magnetic gradient in a magnetic field and those can be used as a contrast enhancement reagent for MRI. Therefore, if magnetite can be accumulated only in tumor tissue, they can afford cancer diagnosis and tumor-specific hyperthermia. To deliver the magnetites toward tumors, two kinds of functional liposomes have been developed, which were “magnetite cationic liposomes(IVICLs)” and “Fab'-conjugating magnetoliposomes (FMLs)”. MCLs were designed for the intratumor injection and showed the high affinity to the tumor cells. On the other hands, FMLs were designed for “missile liposomes” which can accumulate in the tumor by antigens-antibody reaction even in the case of intravascular injection. Here, we review these functional liposomes and discussed how to achieve the ultimate goal for tumor targeting.

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Neutron capture therapy (NCT) is a binary radiotherapy of cancer using the nuclear neutron capture reaction of radiation-producing atoms(sensitizers). In this therapy, compounds can be designed to be biologically inactive, which makes it possible to dose at a large amount to achieve an extremely high concentration required in tumor cells. Boron has been clinically used in treatments of melanoma and brain tumors. While the melanoma has been successfully treated so far, treatment of the brain tumor is still on trial. The key to success in the neutron capture therapy is the control of biodistribution of the sensitizer atoms, boron and gadolinium, including transport through blood-brain barrier, tumor tissue accumulation, intracellular accumulation and subcellular distribution. In this paper, the principle of this therapy, the present status of boron NCT and a challenge to gadolinium NCT are reviewed, mainly focused on the biodistribution of the sensitizer atoms.

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