Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
15 巻, 5 号
選択された号の論文の10件中1~10を表示しています
  • —夢から現実へ—
    菊池 寛
    2000 年 15 巻 5 号 p. 407
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
  • 一杉 安廣
    2000 年 15 巻 5 号 p. 409
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
  • 特集に寄せて
    水島 裕
    2000 年 15 巻 5 号 p. 412-414
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
  • 高分子ナノスフェアを用いたペプチド経粘膜投与製剤の設計
    山本 浩充, 竹内 洋文, 川島 嘉明
    2000 年 15 巻 5 号 p. 415-420
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
    Firstly the superior properties of polymeric nanoparticulate systems to other systems for mucosal peptide delivery as an alternative injection are over looked. Then novel mucosal peptide delivery systems developed by using those particulate systems are reviewed with introducing our systems. The oral mucoadhesive lactide glycolide copolymer (PLGA) nanospheres improved the absorption of calcitonin due to prolonging the retention time and the drug release at the absorption site in rat. Powdered pulmonary systems with PLGA nanospheres and hydroxypropylmethylcellulose phthalate (HPMCP) nanospheres for prolonged and rapid acting peptide delivery systems were successfully developed by us, respectively.
  • コアーシェル型高分子ミセルの構造設計とDDSへの応用
    片岡 一則
    2000 年 15 巻 5 号 p. 421-428
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
    Recently, colloidal carrier systems have been receiving much attention in the field of drug targeting because of their high loading capacity for drugs as well as of their unique disposition characteristics in the body. This paper highlights the utility of polymeric micelles formed through the multimolecular assembly of block copolymers as novel core-shell typed particulates for drug and gene targeting. The process of micellization in aqueous milieu is described in detail based on the differences in the driving force of core segregation, including hydrophobic interaction, electrostatic interaction, metal complexation, and hydrogen bonding of constituent block copolymers. The segregated core embedded in the hydrophilic palisade is shown to function as a reservoir for genes, enzymes, and a variety of drugs with diverse characteristics. Further, the body distribution of polymeric micelles is described to demonstrate their long-circulating characteristics. Focus is placed on the role of the hydrophilic shell in preventing micelles from reticular endothelial recognition, Significant tumor accumulation of polymeric micelles entrapping cytotoxic agents in the core is shown to emphasize their promising utility in tumor-targeting therapy. As an important perspective on carrier systems based on polymeric micelles, their feasibility as non-viral gene vectors is also summarized in this review article.
  • 生体内分解性高分子のDDS製剤への応用
    小川 泰亮
    2000 年 15 巻 5 号 p. 429-436
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
    Microencapsulation techniques, phase separation and solvent evaporation, have been developed for preparation of drug-containing monolithic microcapsules for prolonged release using poly(lactide-co-gtycolide) and copoly(lactic/glycolic) acid. A new technique encapsulating highly water-soluble drugs has been established by modifying the solvent evaporation method using a w/o/w emulsion. The method can completely entrap the highly water-soluble drugs into the microcapsules and can easily prepare the microcapsules in a large scale. The drug releases in a pseudozero order kinetics for several weeks with degradation of the polymers after an initial burst release. Many prolonged release-microcapsules containing water-soluble peptides and proteins were prepared by this method. It is difficult to avoid the initial burst release from the microcapsules containing a water-soluble drug, and a technique to avoid the burst has not been found yet. But an insulin-microcapsule system without the initial burst release has just been presented in the DDS meeting in Japan in this summer. The initial burst problem will be solved in near future.
  • 血中滞留性リポソームによる抗癌剤の処方設計における最適化
    原島 秀吉, 土井 久子, 土橋 麻理, 際田 弘志
    2000 年 15 巻 5 号 p. 437-442
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
    Development of long circulating liposomes (LCL) has become a break through in establishing a drug delivery system using liposomes for antitumor agents. In this study, we have constructed a pharmacokinetic/pharmacodynaniic (PK/PD)-model for doxorubicin (DOX) in mice to analyze the optimum conditions of LCL. Simulation analysis revealed that there existed the optimum release rate of DOX from LCL with a half life approximately 10 hs, regardless of tumor growth rate or tumor sensitivity to DOX. Then, we have tested our PK/PD-model by in vivo survival experiments, which has shown validity of our model. We have also scaled-up the PK/PD-model from mice to humans by substitution of PR parameters for free DOX and LCL. In our preliminary simulations, it was suggested that the optimum release rate of DOX was depended on tumor growth rate as well as tumor sensitivity to DOX, which was different in the case of mice. This PK/PD-modeling will become a useful strategy when we optimize DDS.
  • リポソームの遺伝子治療への応用
    岡本 健太, 水野 正明, 吉田 純
    2000 年 15 巻 5 号 p. 443-446
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
    Liposomes are synthetic lipid vesicles able to entrap drugs or genes within their aqueous compartment and/or lipid bilayer, and they also have been regarded as a useful delivery system, their potential for in vivo gene transfer has been reported. Because liposomes are low levels of toxicity and immunogenicity and they are easy to prepare in large quantity. In addition, cell or tissue specificity can be conferred on liposomes by conjugation or association with specific proteins or antibodies (immunoliposomes). Therefore liposomes are one of the most promising vectors in human gene therapy, especially cationic liposomes. Cationic liposomes hind DNA to form complexes with high affinity to cell membrane or entrap DNA into their compartment, resulting in delivering DNA into cells efficiently. Based on these results, clinical trials of human gene therapy using cationic liposomes have been conducted, Here, we introduce human gene therapies using the liposomes including our cases.
  • 中田 雄一郎, 高橋 嘉輝
    2000 年 15 巻 5 号 p. 449-456
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
    This review is summarized about nanoparticles consisted of triblock-copolymer, poly(L-lactic acid) (PLA)-poly(oxyethylene) (PEG)-PLA. This nanoparticles are characterized using scanning electron microscope (SEM), small-angle X-ray scattering (SAXA) technique and electron spectroscopy for chemical analysis (ESCA). The release of progesterone-loaded PLA-PEG-PLA nanoparticles can be controlled by contents of hydrophilic segments. The release enhancement depended on the PEG content and PEG Mw. Many researchers have been studying the surface modification of nanoparticles using amphoteric compound such as surfactants, albumin, and the use of copolymers, which have both the hydrophilic and hydrophobic domain for the reticuloendothelial system (RES) avoiding system. We showed the possibility of the RES avoiding nanoparticles using PLA-PEG-PLA triblock copolymer as like PLA-PEG diblock copolymer nanoparticles. The contents of PEG and the PEG Mw affected on the RES avoiding ability of nanoparticles. We studied the multiple dose of the PLA-PEG-PLA nanoparticles, and the nanoparticles could control the plasma concentration of drug. The more detail studies, specially the pharmacokinetics and safety will be necessary for clinical use of nanoparticles.
  • 遠藤 浩孝, 熊倉 克頼, 大森 裕正, 奥村 睦男, 浮ケ谷 正, 関 俊暢, 從二 和彦
    2000 年 15 巻 5 号 p. 457-465
    発行日: 2000/09/10
    公開日: 2008/12/26
    ジャーナル フリー
    Lipid microspheres (LM) containing lipophilic prodrug of 5'-deoxy-5-fluorouridine(5'-DFUR), 2', 3'-didecanoyl-5'-deoxy-5-fluorouridine(C 10-5'-DFUR), were prepared. The median diameter of LM containing C 10-5'-DFUR(C 10-5'-DFUR-LM) was about 200 nm, which was unchanged during storage for 1 week at 5°C. We analyzed plasma concentration and cumulative lymphatic transport of drug following oral administration of C 10-5'-DFUR-L to rats, as compared with 5'-DFUR aqueous salutions(5'-DFUR-W) or 5'-DFUR added to LM (5'-DFUR+LM). Effect of simultaneous use of C 10-5'-DFUR and soybean oil or lecithin which is components of LM on lymphatic delivery of drug was also investigated. The plasma concentration of 5'-DFUR rapidly declined following administration of 5'-DFUR-W or 5'-DFUR+LM. In contrast, the plasma concentration of 5'-DFUR was sustained for 24 hr in all cases of formulations containing C 10-5'-DFUR. On the other hand, the cumulative lymphatic transport of the drug following the co-administration of C 10-5'-DFUR and soybean oil or lecithin was higher than 5'-DFUR-W and 5'-DFUR+LM. Especially, in the case of C 10-5'-DFUR-LM, the cumulative lymphatic transport was higher than any other formulation. Those results indicate that administration of lipophilic drug incorporated in LM is effective for directed delivery of the drug to lymph duct, due partly to direct transmucosal passage of the intact LM containing the drug.
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