Enhanced pharmacokinetic and therapeutic of GSH-responsive mPEG-b-P(HPMA)-SGI1776 conjugate for osteosarcoma
Year: 2025
Type: article
Abstract: Introduction: SGI-1776 represents the first serine/threonine kinase inhibitor to be utilized in the treatment of osteosarcoma. It is severely restricted by poor aqueous solubility, short degradation half-life and severe side effect. Methods: -P(N-(2-hydroxypropyl) methylacrylamide) carrier via GSH-responsive disulfide bond. The chemical composition and assembly properties of the conjugate are characterized. Results: The loading capacity of SGI1776 in the conjugate is 22%. The conjugate displays a typical spherical nanoparticle with diameters around 150-260 nm. Cumulative release amounts of SGI1776 can be detected to be 52.9% at the concentration dithiothreitol of 20 mM at 24 h. The hemolysis rate is about 2.35% even when the concentration increases up to 1,000 mg/L. The value of IC50 is about 18.8 μg SGI1776 equiv. per mL for 143b cells. Discussion: The conjugate is more likely to induce apoptosis and can be blocked 143b cells in the S cycle phase. The maximum plasma concentration of the conjugate is attained 0.52 ± 0.092 μg/mL at 4 ± 0 h after the oral administration. The conjugate exhibits better lysosomal escape ability, biocompatibility.
Source: Frontiers in Pharmacology
Authors: Xingchen Shi, Xingchen Shi, Rourou Wang, Zhenghua Zhang, Zixuan Wang, Weibing Xu, Xinhe Shi, Xinhe Shi, Zhe Geng
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G2617552816
OpenAlex ID: W4415457317