Water-stable and finasteride-loaded polyvinyl alcohol nanofibrous particles with sustained drug release for improved prostatic artery embolization - In vitro and in vivo evaluation.

Abstract

Prostatic artery embolization (PAE) has been a well-established treatment for benign prostatic hyperplasia (BPH). To enhance the therapeutic efficacy, a strategy is to use embolic agent preloaded with 5&#x3b1;-reductase inhibitors for localized drug delivery. In this study, finasteride (FNS) was encapsulated into the polyvinyl alcohol (PVA) nanofibers via co-electrospinning technique, followed by heat treatment and cryogenic grinding to convert them into nanofibrous particles as a drug-loaded embolic agent. The FNS was found to be distributed uniformly in PVA nanofibers, and the processed FNS/PVA nanofibrous particles were 272&#xa0;&#x3bc;m in mean particle size. Besides, the studies on the composition, thermal properties, swelling ratio, and water stability of the nanofibers and drug showed that the FNS remained its crystalline state in PVA nanofibers. The heat treatment increased the crystallinity of nanofibers and rendered them water stability. Both FNS and PVA possessed excellent thermal stability at high temperature (150&#xa0;&#xb0;C). In addition, in vitro drug release studies suggested the FNS followed a favorable sustained release up to 744&#xa0;h. Furthermore, the cell viability and hemocompatibility assays indicated the nanofibers possessed excellent cytocompatibility and with no evidence of hemolysis. More importantly, the in vivo PAE procedures on beagles demonstrated the crosslinked FNS/PVA nanofibrous particles exhibited higher embolization efficacy with more obvious prostate volume (PV) reduction compared to crosslinked PVA nanofibrous particles after embolization for 1, 3, and 6&#xa0;months (P&#xa0;<&#xa0;0.05). Therefore, such drug-loaded PVA nanofibrous particles combined physical embolization and localized medical therapy together, which offer great potential to be used as an effective embolic agent for BPH therapy.