Lipidated analogues of luteinizing hormone-releasing hormone (LHRH) reduce serum levels of follicle-stimulating hormone (FSH) after oral administration

A diverse range of diseases involving the reproductive system are treated with luteinizing hormone-releasing hormone (LHRH) agonists which must be administered daily. Currently, an efficient oral delivery system is not available. Here, we show the facile inclusion of lipoamino acids into the peptide...

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Bibliographic Details
Published in:International journal of pharmaceutics 2012-12, Vol.439 (1-2), p.216-222
Main Authors: Mansfeld, Friederike M., Toth, Istvan
Format: Article
Language:English
Subjects:
acids
Administration, Oral
Agonist
agonists
Animals
blood serum
Caco-2 Cells
Follicle Stimulating Hormone - blood
follicle-stimulating hormone
gonadotropin-releasing hormone
Gonadotropin-Releasing Hormone - administration & dosage
Gonadotropin-Releasing Hormone - chemistry
Humans
Lipoamino acid
Lipopeptides - chemistry
luteinization
luteinizing hormone
Luteinizing Hormone - blood
Luteinizing hormone-releasing hormone
Male
oral administration
Oral peptide delivery
Permeability
Rats
Rats, Sprague-Dawley
reproductive system
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Summary:A diverse range of diseases involving the reproductive system are treated with luteinizing hormone-releasing hormone (LHRH) agonists which must be administered daily. Currently, an efficient oral delivery system is not available. Here, we show the facile inclusion of lipoamino acids into the peptide sequence of LHRH, rendering it more stable towards enzymatic degradation, as well as enhancing permeability across Caco-2cell monolayers. Selected LHRH derivatives were tested in vivo by daily oral administration to rats. The size and weight of the sex organs remained unchanged and the levels of LH were stable over the course of the experiment. However, some of the lipidic peptides (3, 8 and 9) were able to reduce serum levels of follicle-stimulating hormone (FSH), an important finding towards the development of orally available LHRH agonists.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2012.09.038