Bae, Do Hyun Bae, Hayeon Yu, Hyung-Seok Dorjsembe, Banzragch No, Young Hyun Kim, Taejung Kim, Nam Hyeong Kim, Jin-Woo Kim, Jiyool Lee, Bok-Soo Kim, Ye Ji Park, Seongchan Khaleel, Zinah Hilal Sa, Deok Hyang Lee, Eui-Chul Lee, Jaecheol Ham, Jungyeob Kim, Jin-Chul Kim, Yong Ho 2024-03-21T09:00:15Z 2024-03-21T09:00:15Z 2024-03-21 2024-06 2192-2640 https://pubs.kist.re.kr/handle/201004/149514 Peptide-drug conjugates (PDCs) are a promising class of drug delivery systems that utilize covalently conjugated carrier peptides with therapeutic agents. 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-penetrating 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-Paradol (PAR) exhibits inhibitory activity against phosphodiesterase 4, which can be utilized for an anti-inflammatory PDC. The transcellular PDC (SDT7-conjugated 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. Transcellular peptides (SDTs) derived from antimicrobial peptides are designed based on cell-penetrating peptides for efficient delivery through the skin barrier. 6-Paradol (PAR) is conjugated with SDT7 to treat psoriatic skin inflammation by inhibiting phosphodiesterase 4. The transcellular peptide-drug conjugate (TM5) exhibits superior efficacy in psoriasis mouse models suggesting a promise for treating inflammatory skin disorders. image English Wiley-Blackwell Peptide-Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis-Like Inflammation Article 10.1002/adhm.202303480 1 Advanced Healthcare Materials, v.13, no.15 Advanced Healthcare Materials 13 15 N scie scopus 001181099300001 2-s2.0-85186895071 Engineering, Biomedical Nanoscience & Nanotechnology Materials Science, Biomaterials Engineering Science & Technology - Other Topics Materials Science Article CELL-PENETRATING PEPTIDES TRANSDERMAL DELIVERY GROWTH MICE peptide-drug conjugates skin barrier transcellular peptide anti-inflammation ginger-driven compounds