Controlled Drug Delivery Systems Using Stimuli-Responsive Electrospun Nanofibers
Chronic diseases account for approximately 71% of the deaths globally. Patients suffering from chronic illness require a constantly changing therapeutic need to keep up with the progression of the disease. However, traditional pharmaceutical treatments fail to provide proper therapy in many ways from high cytotoxicity due to uncontrolled drug release rate to low bioavailability of the drug which requires frequent administration. Therefore, there is a growing interest in developing drug delivery systems to precisely maintain therapeutic drug in the system and protect the active drug molecules from rapid metabolism, thus improving the bioavailability. In this regard, we have developed exogenous stimuli-responsive drug delivery systems based on functionalized electrospun nanofibers.
By utilizing high-performing piezoelectric poly(vinylidene-trifluoroethylene) (P(VDF-TrFE)) nanofibrous membrane, we have developed a mechanical-stimulus responsive drug delivery system based on their piezoelectric effect, where energy conversion occurs from applied mechanical strains to changes in electric potential of P(VDF-TrFE). Using an extracorporeal shockwave system as the mechanical trigger, we demonstrated the control over drug release by regulating nanofiber diameter, and magnitude and frequency of applied mechanical force. We also examined the controllability of the drug delivery system with in vitro and ex vivo models, demonstrating its potential for in vivo applications.
Despite this promising capability of P(VDF-TrFE) nanofibers for controlled drug delivery applications, they need to be surgically removed from the body after drug release due to their non-biodegradable nature. This led us to investigate strategies to enable phagocytosis of the material, which can excrete synthetic non-biodegradable polymer nanofibers from the body. In this regard, we have developed a facile method to fragment polymeric nanofibers into nanorods using colloid electrospinning followed by ultrasonication.
We also developed magneto- & opto-stimulus-responsive nanofibers as an alternative drug delivery system. We functionalized poly(ε-caprolactone) (PCL) nanofibers by integrating superparamagnetic iron oxide nanoparticles (SPIONs) into the fibrous network. By exploiting heat generation from Néel relaxation effect of activated SPIONs under magnetic fields or laser light, we utilized structural changes of thermo-sensitive nanofibers from the heating to trigger drug release. With this composite material, we demonstrated the tunability of drug release by manipulating the SPION loading and stimulus duration.