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Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats4.15 MB
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Journal article
Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats
Evidence-Based Complementary and Alternative Medicine, Vol.2022, pp.1-13
2022
Abstract
Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog (Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the eecacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. is paper investigated the pharmaceutical kinetic proole, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. e results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (C max) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T 1/2 was 4.58 hr, and AUC 0-last was 1890 h × ng/mL. In female rats, C max was 256 ng/mL, with an average drug retention time of 2.96 hr, T 1/2 of 1.33 hr, and AUC 0-last of 740 h × ng/mL. e results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T 1/2 extended, and C max , AUC 0-last , and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. e results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts.
Details
- Title
- Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats
- Authors
- Xiaodan Yang (Author) - First Affiliated Hospital of Guangdong Pharmaceutical UniversityJunjie Li (Author) - First Affiliated Hospital of Guangdong Pharmaceutical UniversityShu Chen (Author) - First People's Hospital of FoshanLiyin Xiao (Author) - First People's Hospital of FoshanDongmin Cao (Author) - First People's Hospital of FoshanXiaolian Wu (Author) - First People's Hospital of FoshanHejie Li (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyGuoying Ni (Corresponding Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyTianfang Wang (Corresponding Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - LegacyGuoqiang Chen (Corresponding Author) - First People's Hospital of FoshanXiao Song Liu (Corresponding Author) - First Affiliated Hospital of Guangdong Pharmaceutical University
- Publication details
- Evidence-Based Complementary and Alternative Medicine, Vol.2022, pp.1-13
- Publisher
- Hindawi Limited
- Date published
- 2022
- DOI
- 10.1155/2022/9869293
- ISSN
- 1741-4288; 1741-427X
- Copyright note
- Copyright © 2022 Xiaodan Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99661597902621
- Output Type
- Journal article
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