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PDCs offer several advantages over traditional drug delivery systems including enhanced target engagement, improved bioavailability, and increased cell permeability. However, the development of efficient transcellular peptides capable of effectively transporting drugs across biological barriers remains an unmet need. In this study, physicochemical criteria based on cell\u2010penetrating peptides are employed to design transcellular peptides derived from an antimicrobial peptides library. Among the statistically designed transcellular peptides (SDTs), SDT7 exhibits higher skin permeability, faster kinetics, and improved cell permeability in human keratinocyte cells compared to the control peptide. Subsequently, it is found that 6\u2010Paradol (PAR) exhibits inhibitory activity against phosphodiesterase 4, which can be utilized for an anti\u2010inflammatory PDC. The transcellular PDC (SDT7\u2010conjugated with PAR, named TM5) is evaluated in mouse models of psoriasis, exhibiting superior therapeutic efficacy compared to PAR alone. These findings highlight the potential of transcellular PDCs (TDCs) as a promising approach for the treatment of inflammatory skin disorders.<\/jats:p>","DOI":"10.1002\/adhm.202303480","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T06:59:14Z","timestamp":1709189954000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Peptide\u2010Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis\u2010Like Inflammation"],"prefix":"10.1002","volume":"13","author":[{"given":"Do Hyun","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Sungkyunkwan University (SKKU)  Suwon 16419 Republic of Korea"},{"name":"Center for Neuroscience Imaging Research (CNIR) Institute for Basic Science (IBS)  Suwon 16419 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayeon","family":"Bae","sequence":"additional","affiliation":[{"name":"SKKU Advanced Institute of Nano Technology (SAINT) Sungkyunkwan University (SKKU)  Suwon 16419 Republic of Korea"},{"name":"Department of Nano Science and Technology Sungkyunkwan University (SKKU)  Suwon 16419 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung\u2010Seok","family":"Yu","sequence":"additional","affiliation":[{"name":"Natural Products Research Institute Korea Institute of Science and Technology (KIST)  Gangneung 25451 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banzragch","family":"Dorjsembe","sequence":"additional","affiliation":[{"name":"Natural Products Research Institute Korea Institute of Science and Technology (KIST)  Gangneung 25451 Republic of Korea"},{"name":"Division of Bio\u2010Medical Science &amp; 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