The novel chitosan particles used simple preparation methods showed high OVA adsorption. When administered intranasally, NP and CC-Emul induced systemic immune response in rats. These findings suggested that CC-Emul and the smaller-size (0.4 microm) NP are effective for targeting to nasal-associated lymphoid tissues (NALTs) in nasal vaccine delivery.

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The proportion of society composed of elderly individuals has risen, indicative of increased longevity.1) Hence, it is of increasing importance to address the medicinal needs of this segment of the population in terms of conventional dosage forms such as powders, tablets and capsules.2) In this regard, to improve the quality of life and treatment compliance of such patients, a fast dissolving oral dosage in the form of rapidly disintegrating tablets (RDT) appears to be a suitable alternative for oral medication, accounting for difficulties associated with swallowing often encountered by this segment of the population. 3,4) Upon placement of tablets of this type within the oral cavity, saliva quickly penetrates into the pores, causing rapid tablet disintegration. Thus, disintegration time is an important property of tablets, but it must be evaluated. In vitro disintegration time can be tested via the Japanese Pharmacopoeia (JP) XIII disintegration test; however, according to the literature, this approach does not appear to be convenient for measuring the disintegration time of RDT. [5][6][7][8] As an alternative to the apparatus described in JP XIII, we developed a novel approach in order to evaluate the disintegration time of RDT employing a CCD camera. We attempted to predict the in vivo disintegration time and to clarify the disintegration mechanism of RDT with this device. For these purposes, three RDT samples were designed with mannitol and different types of binders, including polyvinylpyrrolidone, polyvinylalcohol and hydroxypropylcellulose. ExperimentalMaterials D-Mannitol (Mannit P, Towa Chemical Industry Co., Ltd., Tokyo) (particle size of 52 mm in median diameter by the laser scattering method, LA-910, Horiba, Ltd., Kyoto) was utilized. Polyvinylpyrrolidone JP (PVP-K30, ISP Technologies Inc., New Jersey), 88 mol% hydrolyzed polyvinylalcohol (PVA205C, Kuraray Co., Ltd., Tokyo) and hydroxypropylcellulose JP (HPC-L, Nihon Soda Co., Ltd., Tokyo) were employed as binders. Ethanol was of analytical grade of not less than 99.5% (Junsei Chemical Co., Ltd., Tokyo). Other chemicals were of a commercial grade.Preparation of the Test Tablets Formulations employed in this study are presented in Table 1. Test tablets involved in the evaluation and prediction of oral disintegration were prepared with various binder types and quantities in order to assess the suitability of the CCD-camera method with respect to the examination of in vivo disintegration. A schematic diagram of the preparation technique of the test tablets is shown in Fig. 1. D-Mannitol was crushed in a high-speed mixer equipped with 3-l vessel (Mechanomil MM-10, Okada Seiko Co., Ltd., Tokyo). Binder was dissolved in a solvent composed of a 50% (w/w) ethanol solution. The amount of the solvent used was 13% (w/w) to the tablet weight. D-Mannitol was kneaded with the binder solution in order to achieve uniform moisture. Subsequently, the wet powder was compressed by a novel molding tableting system, 9-11) which consisted of a molding tableting machine and...

Persistent and stable expression of foreign genes has been achieved in mammalian cells by integrating the genes into the host chromosomes. However, this approach has several shortcomings in practical applications. For example, large scale production of protein pharmaceutics frequently requires laborious amplification of the inserted genes to optimize the gene expression. The random chromosomal insertion of exogenous DNA also results occasionally in malignant transformation of normal tissue cells, raising safety concerns in medical applications. Here we report a novel cytoplasmic RNA replicon capable of expressing installed genes stably without chromosome insertion. This system is based on the RNA genome of a noncytopathic variant Sendai virus strain, Cl.151. We found that this variant virus establishes stable symbiosis with host cells by escaping from retinoic acid-inducible gene I-interferon regulatory factor 3-mediated antiviral machinery. Using a cloned genome cDNA of Sendai virus Cl.151, we developed a recombinant RNA installed with exogenous marker genes that was maintained stably in the cytoplasm as a high copy replicon (about 4 ؋ 10 4 copies/cell) without interfering with normal cellular function. Strong expression of the marker genes persisted for more than 6 months in various types of cultured cells and for at least two months in rat colonic mucosa without any apparent side effects. This stable RNA replicon is a potentially valuable genetic platform for various biological applications.