The control over biodistribution and pharmacokinetics is critical to enhance the efficacy and minimize the side effects of therapeutic agents. To address the need for an on-demand drug delivery system for precise control over the release time and the quantity of drugs, we exploited the mechano-responsiveness of piezoelectric poly(vinylidene fluoride-trifluroethylene) (P(VDF-TrFE)) nanofibers for drug delivery applications. The large surface area-to-volume ratio inherent to nanomaterials, together with the transformative piezoelectric properties, allowed us to use the material as an ultrasensitive and mechano-responsive drug delivery platform driven by the direct piezoelectric effect. The intrinsic negative zeta potential of the nanofibers was utilized to electrostatically load cationic drug molecules, where surface potential changes by exogenous mechanical actuation trigger the release of drug molecules. We show that the drug release kinetics of the P(VDF-TrFE) nanofibers depends on the fiber diameter, thus piezoelectric properties. We further demonstrated that the drug release quantity can be tuned by the applied pressure or dose of physiologically safe corporeal shockwaves as a mechanical stimulus in in vitro and ex vivo models. Overall, we demonstrated the utility of piezoelectric electrospun nanofibers for mechano-responsive controlled drug release.

Abstract: Electrospinning is a versatile method for synthesizing nanofibrous structures from nearly all polymers, offering a solution for the industrial‐scale mass production of nanomaterials in a wide range of applications. However, the continuous non‐woven structure intrinsic to electrospun fibers limits their applications, where a smaller length scale is desired. Here, we present a novel method to synthesize polymeric nanofiber‐fragments based on colloid electrospinning of polymer and sacrificial silica nanoparticles, followed by mechanical fracturing with ultrasonication. The size and hydrophobicity of silica nanoparticles are optimized for their improved integration within the polymer matrix, and the controllability of nanofiber‐fragment length by the amount of silica nanoparticle loading, down to 2 µm in length for poly(vinylidene fluoride‐trifluoroethylene) nanofibers with an average fiber diameter of approximately 100 nm, is shown. The resultant nanofiber‐fragments are shown to maintain their material properties including piezoelectric coefficients and their enhanced injectability for drug delivery application is demonstrated with an animal model.