Authors
Yangyi Chen, Yue Wei, Qiao Li, Huajuan He, Hui Chen, Huajing Zhang, Xiaoqing Rong, Xiao Liang, Shiyuan Lin, Wei Zhang
Published in
Carbohydrate polymers. Volume 391. Pages 125843. Nov 01, 2026. Epub Sep 08, 2026.
Abstract
A kind of novel pyrimidine nucleoside (PYN) and silybin (SB) conjugated chitosan (CS) (PYN-CS-SB) polymer micelles were designed for enhancing the oral absorption of doxorubicin (DOX) via the nucleoside transporters located at intestinal epithelial cell. The four types of endogenous PYNs selected respectively as the ligands of the transporter, along with SB, were conjugated to CS. The PYN-CS-SB were synthesized and identified by 1H NMR and FT-IR. The drug-loaded micelles were prepared by ultrasound-assisted self-assembly, and their predominant characteristics, including the microscopic well-dispersed and regular globular shapes with the small particle sizes of 143 nm - 170 nm and the high loading capacities of 9-12%, the amorphous form of DOX encapsulated in micelles, the low critical micelle concentration of 23.1-31.6 μg/mL, and extremely sustained in-vitro release, were shown. Among them, the desoxycytidine (DCD) conjugated micelles (DCD-CS-SB@DOX) exhibited the highest oral bioavailability of 391% versus DOX·HCl. The enhanced absorption based on the nucleoside transporter-mediation, and the dual inhibition of PYN-CS-SB micelles on P-gp efflux and CYP3A4 enzyme, was confirmed by cellular uptake, immunofluorescence, enzyme activity inhibition test. The findings showed the extensive potential of intestinal nucleoside transporter mediated PYN-CS-SB micelles in oral drug delivery.
PMID:
42785882
Bibliographic data and abstract were imported from PubMed on 25 Sep 2026.
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