Electrospun triaxial nanofibers with middle blank cellulose acetate layers for accurate dual-stage drug release.

• Cellulose acetate-based trilayer core-shell fibers with discrete drug distribution. • A modified triaxial electrospinning for producing the complex nanostructure. • The nanofibers can provide an accurate dual-stage release of the loaded drug. • A clear process-nanostructure-performance relationship is exhibited. The combination of complex nanostructures with carbohydrate polymers can provide a strong platform for promoting the development of novel drug delivery systems. In this study, tri-layer core-shell nanofibers F2 with discrete drug distributions were prepared using cellulose acetate (CA) as a key filament-forming polymeric matrix and ketoprofen (KET) as a model drug. The discrete distribution was characterized by inserting a bank CA layer between the CA/KET core layer and the PVP/KET outer layer through a modified triaxial electrospinning. Compared with the traditional core-shell nanofibers F1, the tri-layer nanofibers F2 with drug discrete distributions provided better drug dual-stage release profiles in terms of accurate release contents at the first stage and longer time period sustained release at the second stage. Despite having the same components (drug, soluble PVP, and insoluble CA) and similar linear morphologies, core-shell nanofibers F1 and tri-layer nanofibers F2 exhibited significantly different functional performances in providing dual-stage release. The different structure-performance relationships of the two types of nanofibers have played their important roles on manipulating the accuracy of dual-stage drug controlled release profiles. The mechanism that the tri-layer core-shell nanostructure containing a blank CA middle layer adjusted the drug release behaviors was proposed. [ABSTRACT FROM AUTHOR]