Hydrogen-Bonded Films for Zero-Order Release of Leuprolide.
Animals
Drug Liberation
Hydrogen Bonding
Hydrogen-Ion Concentration
Leuprolide
/ blood
Male
Organ Size
Polyethylene Glycols
/ chemistry
Polymethyl Methacrylate
/ chemistry
Rats, Sprague-Dawley
Spectrophotometry, Ultraviolet
Spectroscopy, Fourier Transform Infrared
Tannins
/ chemistry
Testosterone
/ blood
androgen deprivation therapy
hydrogen bonding
layer-by-layer film
leuprolide
zero-order release
Journal
Macromolecular bioscience
ISSN: 1616-5195
Titre abrégé: Macromol Biosci
Pays: Germany
ID NLM: 101135941
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
19
02
2020
revised:
19
06
2020
pubmed:
8
7
2020
medline:
11
8
2021
entrez:
8
7
2020
Statut:
ppublish
Résumé
Leuprolide has been widely used in androgen deprivation therapy for the treatment of advanced prostate cancer, but its use is still limited due to its short half-life. Herein, hydrogen-bonded layer-by-layer films are fabricated from PEGylated leuprolide (PEG-LEU) and tannic acid (TA). Because of its dynamic nature, the film disintegrates gradually in water and releases PEG-LEU and TA. The in vitro release profile indicated perfect zero-order kinetics, which is explained by the unique release mechanism. When implanted subcutaneously in male rats, the films maintain a constant serum drug level. For a 60-bilayer film, the serum drug level is maintained constant for ≈24 days. No initial burst release is observed, suggesting that the in vivo release also follows zero-order kinetics. Initially, an increase in the level of serum testosterone is induced by the released drug, followed by testosterone suppression to a constant level below the castrate level, which could be maintained as long as a constant serum drug level is maintained. Since the new drug carriers avoid an initial burst release of the drug and maintain a constant serum drug level and hence a constant serum testosterone level below the castrate level, these carriers are highly promising for androgen deprivation therapy.
Identifiants
pubmed: 32633851
doi: 10.1002/mabi.202000050
doi:
Substances chimiques
Tannins
0
Polyethylene Glycols
3WJQ0SDW1A
Testosterone
3XMK78S47O
Polymethyl Methacrylate
9011-14-7
Leuprolide
EFY6W0M8TG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2000050Informations de copyright
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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