Drug-loaded electrospun fibers with stabilizing sheath: prevent post-fabrication drug precipitation-induced recrystallization and controlling Molecular Relaxation for controlled release.

Burst release and insufficient sustained release continue to pose significant challenges in the clinical application of pirfenidone-loading ureteral stents for treating ureteral strictures. Herein, we present a coaxial electrospun drug-loading membrane featuring an outer stabilizing sheath designed to reduce the initial burst release and enable sustained delivery of pirfenidone (PFD). The membrane consists of aligned microfibers with a core of poly(L-lactide-co-ε-caprolactone) (PLCL) encapsulating PFD, surrounded by a poly(L-lactic acid) (PLLA) sheath that acts as a diffusion-resisting and release controlling sheath. In vitro drug release experiments are conducted alongside with detailed physicochemical and mechanical analyses. The results demonstrate that the sheath effectively suppresses drug precipitation during the drying process after electrospinning. Consequently, it obviously decreases the initial burst release by about 22% in 3 hours and by around 11% in 48 hours compared with PLLA uniaxial drug-loading membrane. It is followed by a sustained release profile over 48 hours, with a total drug release exceeding 90%. Meanwhile, the molecular orientation relaxation is mitigated by about 29.9% within the first 24 hours by the sheath. Then, there is an approximately linear molecular orientation relaxation at the following stage. Furthermore, the membrane preserves its structural integrity and maintains desirable mechanical properties, such as strength and ductility, throughout the release period. These findings suggest that the stabilizing sheath is a promising method for modulating drug release profiles, offering a valuable platform for developing advanced covered stents.