(M1130-01-05) Novel Cell-Penetrating Peptide-Based Therapy for Treating Atopic Dermatitis

Purpose: The objective of the research is to nanoformulate a new peptide with cell penetration properties and anti-inflammatory efficacy for the application in atopic dermatitis.

Methods: Peptides with cell-penetrating and anti-inflammatory properties were screened and evaluated for their anti-inflammatory effects. The peptide-loaded nanoparticles were prepared using thin-film hydration methods and their physicochemical characterization was assessed. To evaluate overall efficacy, cytotoxicity assays and assessment of inflammation-related factor expression were conducted. Additionally, efficacy evaluation was performed in an atopic animal model.

Results: The selected peptide, RMSP1, has been confirmed to possess both cell-penetrating properties and anti-inflammatory effects. Moreover, upon palmitoylation and subsequent peptide treatment, there was a significant decrease in the expression levels of inflammation-related genes and proteins, thereby enhancing the anti-inflammatory effect. To reduce the peptide’s cytotoxicity and enhance its stability, it was formulated into liposomes and micelles, resulting in sizes of 120nm or less and a narrow size distribution.[1] Both cell viability assays and PCR results confirmed that when the peptide was formulated into nanoparticles, cytotoxicity decreased while the expression of inflammatory mediators also decreased. Finally, in vivo experiments in mice with induced atopy demonstrate a decrease in serum IgE levels and alleviation of atopic symptoms upon peptide-loaded nanoparticles administration.

Conclusion: The developed peptide demonstrates both cell-penetrating and anti-inflammatory properties, and the nano-formulation research indicates reduced toxicity and improved anti-inflammatory efficacy. Therefore, it is suggested that this peptide nanoformulation could serve as a promising new option for the treatment of atopic dermatitis.

References: [1] A. Zeb, et al. Controlled release and targeted drug delivery with poly (lactic-co-glycolic acid) nanoparticles: Reviewing two decades of research, J. Pharm. Invest., 2022, 52 , 683 —724.


Figure 1 Evaluating anti-inflammatory effects of the RMSP1 peptide. Relative expression amounts of inflammatory-associated (a) genes analyzed by qRT-PCR and (b) proteins analyzed by western blots in RMSP1-treated HaCaT cells. Expression changes of inflammatory-associated (c) genes analyzed by qRT-PCR and (d) proteins analyzed by western blots in Pal-RMSP1-treated HaCaT cells.


Figure 2 In vitro evaluation of Pal-RMSP1. (a) and (b) Cell viability and (c) changes of relative TNF-α expression of sample-treated cells via real-time PCR analysis. (c) Change of relative TNF-α release of sample-treated RAW 264.7 cells via ELISA analysis.Evaluating anti-inflammatory effects of the RMSP1 peptide. Relative expression amounts of inflammatory-associated (a) genes analyzed by qRT-PCR and (b) proteins analyzed by western blots in RMSP1-treated HaCaT cells. Expression changes of inflammatory-associated (c) genes analyzed by qRT-PCR and (d) proteins analyzed by western blots in Pal-RMSP1-treated HaCaT cells.


Figure 3 Evaluation of Pal-RMSP1 against the oxazolone-induced atopy animal model. (a) Schematic description of the experimental design. (b) Effect of Pal-RMSP1 on serum IgE concentrations. (c) Histopathological features of skin lesions after sample treatment. (d) H&E-stained ear skin sections of mice treated with each sample. (e) Thickness of ear measured as the distance from the basal to the upper granular layer.