View : 344 Download: 68
PEGylation improves the therapeutic potential of dimerized translationally controlled tumor protein blocking peptide in ovalbumin-induced mouse model of airway inflammation
- Title
- PEGylation improves the therapeutic potential of dimerized translationally controlled tumor protein blocking peptide in ovalbumin-induced mouse model of airway inflammation
- Authors
- Seo, Hyeran; Bae, Hae-Duck; Pyun, Haejun; Kim, Bo-Gyu; Lee, Sang-Il; Song, Jin-Sook; Lee, Kyunglim
- Ewha Authors
- 이경림
- SCOPUS Author ID
- 이경림
- Issue Date
- 2022
- Journal Title
- DRUG DELIVERY
- ISSN
- 1071-7544
1521-0464
- Citation
- DRUG DELIVERY vol. 29, no. 1, pp. 2320 - 2329
- Keywords
- PEGylation; dimerized TCTP-binding peptide 2 (dTBP2); dimerized translationally controlled tumor protein (dTCTP); histamine-releasing factor (HRF); allergic airway inflammation
- Publisher
- TAYLOR &
FRANCIS LTD
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Dimerized translationally controlled tumor protein (dTCTP) initiates a variety of allergic responses in mouse models and that dTCTP-binding peptide 2 (dTBP2) attenuates the allergic inflammation by targeting dTCTP. However, the usefulness of peptide-based drugs is often limited due to their short half-lives, rapid degradation, and high levels of clearance after systemic administration. In this study, we chemically conjugated dTBP2 with 10 kDa polyethylene glycol (PEG) to improve its therapeutic potential. N-terminal mono-PEGylated dTBP2 (PEG-dTBP2) was characterized by in vitro bioactivity assay, pharmacokinetics study, and in vivo efficacy. When compared to the unmodified dTBP2, PEG-dTBP2 reduced proinflammatory cytokine IL-8 secretion in human bronchial cells by 10 to 15% and increased plasma half-life by approximately 2.5-fold in mice. This study specifically demonstrated that PEG-dTBP2 shows higher inhibitory action against ovalbumin (OVA)-induced airway inflammation in mice compared to dTBP2. Importantly, PEG-dTBP2, when administered once at 1 mg/kg, significantly reduced the migration of inflammatory cells and the levels of cytokines in the bronchoalveolar lavage fluids as well as OVA-specific IgE levels in serum. In addition, the degree of goblet cell hyperplasia and mucus secretion were significantly attenuated in the PEG-dTBP2 group compared with the control group. These results suggest that PEG-dTBP2 can be considered a potential candidate drug for regulating allergic inflammation.
- DOI
- 10.1080/10717544.2022.2100511
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
-
PEGylation improves the therapeutic potential of dimerized translationally controlled tumor protein blocking peptide in ovalbumin induced mouse model.pdf(2.34 MB)
Download
- Export
- RIS (EndNote)
- XLS (Excel)
- XML