Programmable 3D printed conductive polymers for releasing neutrally-charged drugs

Conductive polymers (CPs) are an exciting class of functional polymers that can respond to a voltage stimulus. As a drug delivery system (DDS), the voltage applied to CPs can modulate drug release, offering unprecedented spatial and temporal control as we strive for precision and personalised medicines. However, this requires the drug to be charged in order to respond to a voltage stimulus, where unfortunately there are numerous clinically-relevant drugs that are neutrally-charged. Herein, we propose an innovative solution that leverages charged polymeric particles as an intermediary vehicle. In this investigation, we electrospray paracetamol, a neutrally-charged drug, with poly(lactic-co-glycolic acid) (PLGA) to obtain drug-loaded microparticles with an overall negative charge of -53.01 ± 2.71 mV. The drug-loaded microparticles were then mixed with a CP and subsequently three-dimensionally (3D) printed into films. The films were subjected to voltages of 0, +1 and -1 V, where multivariate analysis of variance (MANOVA) revealed statistical significance in their drug release profiles. Applying -1 V (i.e., the same charge as the PLGA particle) resulted in a three-fold increase in drug release compared to 0 V (i.e., passive release), increasing from 9.82 ± 1.32% to 29.03 ± 2.34%. Furthermore, the platform was confirmed to respond and exhibit pulsatile release when switching the voltage “on-and-off”. Another benefit of leveraging PLGA discovered included sustained drug release and is discussed. The findings suggest that neutrally-charged drugs can be made voltage-responsive by leveraging charged polymeric particles, and signals a promising strategy for widening the clinical impact of CPs as DDSs.