Therapeutic Effects of 30 nm Cyclosporin A-Loaded Nanoparticles Using PLGA-PEG-PLGA Triblock Copolymer for Transdermal Delivery in Mouse Models of Psoriasis
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作者:
Kagawa, Akira
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Tokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, JapanTokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, Japan
Kagawa, Akira
[1
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Sato, Akira
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Tokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, JapanTokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, Japan
Sato, Akira
[1
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Makino, Kimiko
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Tokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, JapanTokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, Japan
Makino, Kimiko
[1
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Takeuchi, Issei
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Tokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, Japan
Josai Int Univ, Fac Pharmaceut Sci, 1 Gumyo, Togane 2838555, JapanTokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, Japan
Takeuchi, Issei
[1
,2
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机构:
[1] Tokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda 2788510, Japan
[2] Josai Int Univ, Fac Pharmaceut Sci, 1 Gumyo, Togane 2838555, Japan
This study aimed to evaluate the effectiveness of poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) as a drug carrier in the treatment of psoriasis. Nanoparticles containing cyclosporin A (CsA) were prepared, and their cytotoxicity and skin irritation properties were investigated. These results revealed that the nanoparticles themselves had no obvious cytotoxicity or skin irritation effects. Furthermore, it was shown that loading CsA into nanoparticles promoted its cellular uptake. The therapeutic effect of CsA-loaded PLGA-PEG-PLGA nanoparticles on psoriasis was evaluated using a mouse model of psoriasis induced by imiquimod. In psoriatic skin, we confirmed that nanoparticles penetrate deep into the skin. Furthermore, it was suggested that by using PLGA-PEG-PLGA, drug carriers could reach the dermal layer, which is the target site for psoriasis treatment. The observation of skin sections after the treatment experiment showed that excessively proliferated keratinocytes were restored to an almost normal state by using PLGA-PEG-PLGA nanoparticles as drug carriers. Additionally, the quantitative measurement results for cytokines revealed that the levels of TNF-alpha, IL-17A, and IL-22 were significantly decreased compared with those of the group to which CsA suspended in a 20% ethanol solution was administered. These results indicate that PLGA-PEG-PLGA nanoparticles are promising drug carriers for the transdermal administration of CsA.
机构:
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, ChibaFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba
Kagawa A.
Makino K.
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Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba
Center for Drug Delivery Research, Tokyo University of Science, 2641, Yamazaki, Noda, ChibaFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba
机构:Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Ctr Controlled Chem Delivery, Salt Lake City, UT 84112 USA
Choi, S
Baudys, M
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机构:Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Ctr Controlled Chem Delivery, Salt Lake City, UT 84112 USA
Baudys, M
Kim, SW
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Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Ctr Controlled Chem Delivery, Salt Lake City, UT 84112 USAUniv Utah, Dept Pharmaceut & Pharmaceut Chem, Ctr Controlled Chem Delivery, Salt Lake City, UT 84112 USA