###### Abstract  
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 cyclospor 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 akin, 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. Keywords:transdermal delivery; cyclospor A; nanoparticle; PLGA-PEG-PLGA; PLGA; PLGA; psoriasis; mouse +
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the barrier function of the stratum corneum mainly against foreign substances from the outside of the body is lowered. It was reported that psoriatic lesions are highly infiltrated by immune cells [6; 7]. Pro-inflammatory cytokines produced by these cells contribute to the pathogenesis of psoriasis by causing the activation of keratinocytes and other resident skin cells [5]. Lesional T cells that secrete IL-17 (Th17 cells) were recognized as important contributors to the pathogenesis of psoriasis. Th17 cells are involved in the pathogenesis of many autoimmune and inflammatory diseases such as psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease [8]. Symptoms of psoriasis are caused by Th17 cells overexpressing cytokines IL-17A and IL-22. In addition, Th17 cells induced from naive T cells are maintained by IL-23 produced from dendritic cells. These IL-23-producing dendritic cells are called Tip-DCs and are major TNF-\(\alpha\) producing cells [7]. Therefore, in psoriasis, TNF-\(\alpha\), IL-23, and IL-17A continuously work from the upstream to form eruptions [5]. Recently, the T helper (Th)-17/interleukin (IL)-23 axis has attracted attention in the treatment of psoriasis., as humanized anti-human IL-23p19 monoclonal antibody and humanized anti-human IL-17 monoclonal antibody, risankizumab and secukinumab were newly developed, and studies on verifying their therapeutic effects were reported [9; 10]. Conventional drugs such as cyclospor, which can be administered orally, and tacrolimus, which is used externally, are still used. In the previous study, we successfully prepared cyclospor A (CsA)-loaded nanoparticles with a mean diameter of 30 nm using poly(DL-lactide-_co_-glycolide)-_block_-poly(ethylene glycol)-_block_-poly(DL-lactide-_co_-glycolide) triblock copolymers (PLGA-PEG-PLGA). It was shown that PLGA-PEG-PLGA nanoparticles are better able to penetrate the skin than PLGA nanoparticles and have higher drug delivery to deep within the skin [11]. CsA is a highly lipophilic and relatively large-molecular-weight (1202 Da) drug. Its cyclic structure and large diffusional cross-section make it difficult to penetrate deep into the skin [12]. In psoriatic skin, the barrier function against external foreign substances, mainly the stratum corneum, is lowered.