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.
Keywords: electrospun fibers; mechano-sensitive; on-demand drug delivery; piezoelectric; poly(vinylidene trifluoroethylene).