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Peptide-Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis-Like Inflammation.
- Source :
-
Advanced healthcare materials [Adv Healthc Mater] 2024 Jun; Vol. 13 (15), pp. e2303480. Date of Electronic Publication: 2024 Mar 09. - Publication Year :
- 2024
-
Abstract
- 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.<br /> (© 2024 Wiley‐VCH GmbH.)
- Subjects :
- Animals
Humans
Mice
Keratinocytes drug effects
Keratinocytes metabolism
Inflammation drug therapy
Inflammation metabolism
Skin metabolism
Skin drug effects
Drug Delivery Systems methods
Cell-Penetrating Peptides chemistry
Cell-Penetrating Peptides pharmacology
Cell-Penetrating Peptides pharmacokinetics
Phosphodiesterase 4 Inhibitors chemistry
Phosphodiesterase 4 Inhibitors pharmacology
Phosphodiesterase 4 Inhibitors pharmacokinetics
Psoriasis drug therapy
Psoriasis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2192-2659
- Volume :
- 13
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Advanced healthcare materials
- Publication Type :
- Academic Journal
- Accession number :
- 38421096
- Full Text :
- https://doi.org/10.1002/adhm.202303480