Hydrogen-Bonded Films for Zero-Order Release of Leuprolide

Fu, M (Fu, Mian)^{[ 1,2 ]} ; Zhuang, XM (Zhuang, Xiaomei)^{[ 3 ]} ; Zhang, TH (Zhang, Tianhong)^{[ 3 ]} ; Guan, Y (Guan, Ying)^{[ 1,2 ]} ; Meng, QB (Meng, Qingbin)^{[ 3 ]} ; Zhang, YJ (Zhang, Yongjun)^{[ 1,2 ]}

MACROMOLECULAR BIOSCIENCE, 2020, 文献号: 2000050

DOI: 10.1002/mabi.202000050

摘要

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 approximate to 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.