Hydrogen‐Bonded Films for Zero‐Order Release of Leuprolide

Abstract

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.

Physicochemical and Biopharmaceutical Controllability of New Self-Assembled Fatty Acid Conjugated Leuprolide for the Enhanced Anticancer Activity

“…In water solution, LEU and LFCs spectra were depicted with a single large negative peak at around 200 nm, featuring a major random coil structure. 33 In the solution of 50% TFE, three LFCs stilled performed predominantly random coil structures like that of LEU with a single negative peak at around 203 nm. Herein, the remained unchanged secondary structure of LEU in water and 50% TFE could be affected by the number of amino acids (9 amino acids) contained in the peptide chain, as compared to CM4 (35 amino acids) or CAMEL (15 amino acids) as reported in previous studies.…”

Single-injection COVID-19 subunit vaccine elicits potent immune responses

“…In addition, since both TA and PEG have a narrow molecular weight distribution, k 1 could be regarded as constant. Therefore, disintegration rate of the film is constant [ 23 , [29] , [30] , [31] , [32] , [33] ].…”

Correlation of Solubility Thermodynamics of Glibenclamide with Recrystallization and In Vitro Release Profile

“…The present study is focused mainly on the screening of GLN solvate forms, which could provide an improved in vitro release profile along with high purity in the tablets with respect to impurities and degradation products during the manufacturing processes (high-shear wet granulation, drying, and tableting) and physiological conditions (pH and temperature) [23,24]. The goal of the study is to determine the solubility of GLN in various organic solvents and aqueous mixtures.…”