著者

Yukihiko Aramaki Hidetoshi Arima Mamiko Takahashi Eriko Miyazaki Takatoshi Sakamoto Seishi Tsuchiya

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.10, pp.1461-1466, 2003 (Released:2003-10-01)

参考文献数

23

被引用文献数

4 5

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The intradermal delivery of an antisense oligonucleotide was examined by iontophoresis. In this experiment, the antisense sequence of [32P]-labeled phosphodiester oligonucleotide ([32P]D-oligo, 18-mer) hybridizing to mouse interleukin 10 (IL-10) mRNA was used as a model D-oligo. In in vitro iontophoretic experiments, isolated hairless mouse skin was used with a horizontal diffusion cell. The enhancing effect of pulse depolarization (PDP) iontophoresis on the [32P]D-oligo permeation through the skin was better, and the skin irritation was less, than those of constant direct current (CDC) iontophoresis. The apparent fluxes of [32P]D-oligo were enhanced with the increasing current densities and [32P]D-oligo concentrations in the donor solution, whereas the enhanced flux decreased with the increasing NaCl concentrations in the donor solution. An optimum electric current was observed for the intradermal delivery of [32P]D-oligo, and intact [32P]D-oligo was detected within the skin after iontophoresis for 6 h. These results suggest that PDP iontophoresis may be useful for the intradermal delivery of antisense oligonucleotides.

著者

Masamichi Inoue Kyosuke Muta Ahmed Fouad Abdelwahab Mohammed Risako Onodera Taishi Higashi Kenta Ouchi Mitsuharu Ueda Yukio Ando Hidetoshi Arima Hirofumi Jono Keiichi Motoyama

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.11, pp.1660-1668, 2022-11-01 (Released:2022-11-01)

参考文献数

37

被引用文献数

4

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Hereditary amyloidgenic transthyretin (ATTR) amyloidosis is caused by a genetic point-mutated transthyretin such as TTR Val30Met (TTR V30M), since it forms protein aggregates called amyloid resulting in the tissue accumulation and functional disorders. In particular, ATTR produced by retinal pigment epithelial cells often causes ATTR ocular amyloidosis, which elicits deterioration of ocular function and ultimately blindness. Therefore, development of novel therapeutic agents is urgently needed. Genome-editing technology using Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas9) system is expected to be a therapeutic approach to treat genetic diseases, such as ATTR amyloidosis caused by a point mutation in TTR gene. Previously, we reported that glucuronylglucosyl-β-cyclodextrin conjugated with a polyamidoamine dendrimer (CDE) had excellent gene transfer ability and that underlying dendrimer inhibited TTR aggregation. Conversely, folate receptors are known to be highly expressed in retina; thus, folate has potential as a retinal target ligand. In this study, we prepared a novel folate-modified CDE (FP-CDE) and investigated its potential as a carrier for the retinal delivery of TTR-CRISPR plasmid DNA (pDNA). The results suggested that FP-CDE/TTR-CRISPR pDNA could be taken up by retinal pigment epithelial cells via folate receptors, exhibited TTR V30M amyloid inhibitory effect, and suppressed TTR production via the genome editing effect (knockout of TTR gene). Thus, FP-CDE may be useful as a novel therapeutic TTR-CRISPR pDNA carrier in the treatment of ATTR ocular amyloidosis.

著者

Nasrul Wathoni Taofik Rusdiana Aliya Nur Hasanah Ahmad Muhtadi Elasari Dwi Pratiwi Ripa’tul Mahmudah Ahmed Fouad Abdelwahab Mohammed Maiko Okajima Tatsuo Kaneko Hidetoshi Arima

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.67, no.8, pp.849-854, 2019-08-01 (Released:2019-08-01)

参考文献数

49

被引用文献数

7

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Regenerative therapy with keratinocyte growth factor (KGF) is a novel therapeutic approach for treatment of chronic wounds. However, KGF cannot be used directly to the wound site due to its physicochemical instability. In previous study, sacran, a natural megamolecular polysaccharide, showed potential properties as a biomaterial for hydrogel film in wound healing. In this study, we fabricated sacran hydrogel film containing KGF (Sac/KGF-HF) and evaluated the effects of Sac/KGF-HF on fibroblasts migration and re-epithelialization process. We successfully prepared a homogenous and -amorphous Sac/KGF-HF by a casting method. In addition, Sac/KGF-HF had a high swelling ratio and flexibility. Sac/KGF-HF promoted a migration process of NIH3T3 cells and improved wound healing ability in mice with a percentage of wound closure reaching 90.4% at 9 d. Interestingly, the addition of KGF in Sac-HF considerably increased the number of epithelial cells compared to control, which is important in the re-epithelialization process. It could be concluded that KGF in Sac-HF has the potential for promoting Sac-HF abilities in wound healing process.

著者

Taishi Higashi Daisuke Iohara Keiichi Motoyama Hidetoshi Arima

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.66, no.3, pp.207-216, 2018-03-01 (Released:2018-03-01)

参考文献数

174

被引用文献数

40

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Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry. However, it is not a major domain in the pharmaceutical field. In this review, we propose a new concept in pharmaceutical sciences termed “supramolecular pharmaceutical sciences,” which combines pharmaceutical sciences and supramolecular chemistry. This concept could be useful for developing new ideas, methods, hypotheses, strategies, materials, and mechanisms in pharmaceutical sciences. Herein, we focus on cyclodextrin (CyD)-based supermolecules, because CyDs have been used not only as pharmaceutical excipients or active pharmaceutical ingredients but also as components of supermolecules.