Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model

doi:10.3389/fphar.2020.00058

科研成果详情

题名	Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model
作者	Zhang, Li 1,2,3; Huang, Tongzhou 1,2; Bi, Jianing1,2; Zheng, Yingying 1,2; Lu, Chao 1,2; Hui, Qi2; Wang, Xiaojie 1,2,3; Lin, Xiaohua1,2,3
发表日期	2020-02-21
发表期刊	FRONTIERS IN PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	rh-aFGF carbomer 940 hydrogel long-term toxicity immunotoxicity neutralization antibody
其他关键词	FIBROBLAST-GROWTH-FACTOR ; IN-VITRO
摘要	We developed a highly stable recombinant human acidic fibroblast growth factor (rh-aFGF) carbomer 940 hydrogel for wound healing. This study aimed to reveal toxicity target organs and the toxicity dose-response in the long-term administration of rh-aFGF carbomer 940 hydrogel in a rabbit skin wound model. New Zealand rabbits were topically administrated rh-aFGF carbomer 940 hydrogel at a daily dose of 900 IU/cm(2), 1,800 IU/cm(2), and 3,600 IU/cm(2) for 28 days. Lyophilized rh-aFGF agent was used as the positive control group. General behavior, serum chemistry, skin irritation, immunogenicity, immunotoxicity, and histopathology were analyzed at designated time points. Results revealed that food intake, body weight, body temperature, heart rate, and eye examinations were all normal, suggesting no obvious toxicity induced by the rh-aFGF hydrogel. Medium and high dose rh-aFGF hydrogel groups and the positive control group displayed increased cell numbers in the local lymph nodes near the site of administration, likely caused mesenteric lymph node follicular hyperplasia, and this observation was alleviated after 14 days of recovery. Immunogenicity studies demonstrated that the serum antibody titer against rh-aFGF increased with the duration and number of drug applications but were not neutralization antibodies. After administration stopped, antibody titer decreased and disappeared in some mice. In summary, the safe dose for long-term administration of rh-aFGF carbomer 940 hydrogel for persistently damaged skin was 900 IU/cm(2), which is 10 times that of the proposed clinical dosing.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81601695]; Science and Technology Project of Wenzhou [Y20180150]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1663-9812
卷号	11 页码:58
DOI	10.3389/fphar.2020.00058
页数	8
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000523683200001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	32153396
PMC记录号	PMC7046797
SCOPUSEID	2-s2.0-85081254507
通讯作者地址	[Wang, Xiaojie]The Department of Dermatology of the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology;Pharmacology (medical)
引用统计	被引频次：9[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/15256
专题	附属第一医院_皮肤科药学院（分析测试中心）
通讯作者	Wang, Xiaojie
作者单位	1.The Department of Dermatology of the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.School of Pharmacy,Wenzhou Medical University,Wenzhou,China; 3.Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors,Biomedical Collaborative Innovation Center of Wenzhou,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 温州医科大学
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Zhang, Li,Huang, Tongzhou,Bi, Jianing,et al. Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model[J]. FRONTIERS IN PHARMACOLOGY,2020,11:58.
APA	Zhang, Li., Huang, Tongzhou., Bi, Jianing., Zheng, Yingying., Lu, Chao., ... & Lin, Xiaohua. (2020). Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model. FRONTIERS IN PHARMACOLOGY, 11, 58.
MLA	Zhang, Li,et al."Long-Term Toxicity Study of Topical Administration of a Highly-Stable rh-aFGF Carbomer 940 Hydrogel in a Rabbit Skin Wound Model".FRONTIERS IN PHARMACOLOGY 11(2020):58.