Gemcitabine-Loaded PLGA Ureteral Stents via Sacrificial Electrospinning: Release Kinetics and Anti-Tumor Mechanism

The rational design of drug-eluting polymeric implants requires a fundamental understanding of macromolecular structure, degradation, and transport kinetics. Herein, we report the structure-property-function relationships of a gemcitabine-loaded poly(lactic-co-glycolic acid) (PLGA) nanofibrous matrix, engineered into a precise tubular architecture via a modified sacrificial template electrospinning strategy. Physicochemical characterization elucidated excellent drug-polymer compatibility, enabling the homogeneous, amorphous dispersion of gemcitabine within the PLGA network. Macroscopically, the engineered matrix overcomes traditional electrospinning defects, retaining essential mechanical robustness (specifically radial compression recovery) during its functional window. Crucially, the polymeric network exhibits a highly regulated, biphasic release profile extending over 30 days, which is fundamentally governed by a coupled Fickian diffusion and bulk polymer erosion mechanism (anomalous transport, n = 0.53). As a biological validation of this tailored macromolecular design, the construct was evaluated in a subcutaneous xenograft model of upper tract urothelial carcinoma (UTUC). The spatiotemporally controlled release translated into a potent 70.5% tumor inhibition rate with negligible systemic toxicity. Immunohistochemical analysis confirmed that the locally delivered drug retained its bioactivity, effectively triggering a specific P53/P21/Cyclin B-mediated G2/M phase cell cycle arrest. Consequently, this study establishes a robust fundamental paradigm for designing functionalized polymeric architectures tailored for localized cancer therapy.