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Nanoparticles induced by embedding self‐assembling cassette into glucagon‐like peptide 1 for improving in vivo stability
Author(s) -
Li Ying,
Cui Tao,
Kong Xiaodong,
Yi Xiulin,
Kong Dexin,
Zhang Jianning,
Liu Changxiao,
Gong Min
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701033rrr
Subject(s) - in vivo , embedding , chemistry , nanoparticle , peptide , nanotechnology , biochemistry , materials science , computer science , biology , microbiology and biotechnology , artificial intelligence
The multiple physiologic characteristics of glucagon‐like peptide 1 (GLP‐1) make it a promising drug candidate for treating type 2 diabetes mellitus. However, the half‐life of GLP‐1 is short as a result of degradation by dipeptidyl peptidase IV and renal clearance. Stabilizing GLP‐1 is therefore critical for its use in drug development. Self‐assembling peptides are a class of peptides that undergo spontaneous assembly into ordered nanostructures. Recently, studies of self‐assembling peptides as drug carriers have increased because of their enhanced stability. In the present study, GLP‐1 was modified to incorporate the structural characteristics of self‐assembling peptides aiming to generate a self‐assembling GLP‐1 derivative. Receptor binding capacity and insulinotropic effects were measured to investigate the physiologic functions of GLP‐1, along with morphologic approaches to observe supramolecular formation on self‐assembly at the nano scale. Finally, blood glucose regulation and body weight were monitored after administration of selected derivatives. Our findings revealed that cadyglp1e and cadyglp1m both exhibited improved stability even though different nanoshapes were observed for these two self‐assembling peptides. Both cadyglp1e and cadyglp1m retained glucoregulatory activity after insulin stimulation and were potent drug candidates for long‐acting GLP‐1 derivatives to treat type 2 diabetes mellitus. Our findings support the feasibility of introducing self‐assembly functions into peptides with poor stabilities, such as GLP‐1.—Li, Y., Cui, T., Kong, X., Yi, X., Kong, D., Zhang, J., Liu, C., Gong, M. Nanoparticles induced by embedding self‐assembling cassette into glucagon‐like peptide 1 for improving in vivo stability. FASEB J. 32, 2992–3004 (2018). www.fasebj.org