Electrospun fibers loaded with ball-milled poly(n-isopropylacrylamide) microgel particles for smart delivery applications

Stimuli-responsive electrospun fibers loaded with therapeutic agents for smart delivery are attractive biomedical applications. However, development of such fibers requires the use of complex chemical processes that can induce toxicity, reduce fiber quality, or prohibit fiber electrospinnablity. To address these challenges, core-shell structured fibers capable of temperature-controlled delivery of nanoparticles were developed. The fiber core contained an aqueous suspension of poly(n-isopropylacrylamide) (PNIPAM) microgel particles and silver nanoparticles (model antibacterial drug). A novel use of ball-milling was applied to produce microgel particles with an average hydrodynamic diameter of 511 +/- 100 nm. The ball-milling technique was developed to avoid the current complex chemical processes for syntheses of microgels, and to address the need for high-yield techniques in industrial manufacturing. The results show that the thermoresponsive properties of the PNIPAM hydrogel particles were preserved during the ball-milling process. The fiber shell formed a strong structure matrix, regulated the nanoparticles release pathway (through open pores formed via selective dissolution of porogen), and served as a barrier to prevent direct contact of microgel particles with tissues. This core-shell fiber design allows for the future application of various therapeutic agents, including fragile and bioactive agents, and microgel particles with special properties.