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Open Access Publications from the University of California

Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC Riverside Electronic Theses and Dissertations (2020)

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.

    Cover page: Controlled Drug Delivery Systems Using Stimuli-Responsive Electrospun Nanofibers
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2021)
    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.
      Cover page: Mechano-Responsive Piezoelectric Nanofiber as an On-Demand Drug Delivery Vehicle
      • Article
      • Peer Reviewed
      UC Riverside Previously Published Works (2022)
      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.
        Cover page: A facile method for synthesizing polymeric nanofiber‐fragmentsCreative Commons 'BY-NC-SA' version 4.0 license
        • Article
        • Peer Reviewed
        UC Riverside Previously Published Works (2021)
        Due to dissimilarities in genetics and metabolism, current animal models cannot accurately depict human neurological diseases. To develop patient-specific in vitro neural models, a functional material-based technology that offers multi-potent stimuli for enhanced neural tissue development is devised. An electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) nanofibrous scaffold is systematically optimized to maximize its piezoelectric properties while accommodating the cellular behaviors of neural stem cells. Hydro-acoustic actuation is elegantly utilized to remotely activate the piezoelectric effect of P(VDF-TrFE) scaffolds in a physiologically-safe manner for the generation of cell-relevant electric potentials. This mechano-electrical stimulation, which arose from the deflection of the scaffold and its consequent generation of electric charges on the scaffold surface under hydro-acoustic actuation, induces the multi-phenotypic differentiation of neural stem cells simultaneously toward neuronal, oligodendrocytic, and astrocytic phenotypes. As compared to the traditional biochemically-mediated differentiation, the 3D neuron-glial interface induced by the mechano-electrical stimulation results in enhanced interactions among cellular components, leading to superior neural connectivity and functionality. These results demonstrate the potential of piezoelectric material-based technology for developing functional neural tissues in vitro via effective neural stem cell modulation with multi-faceted regenerative stimuli.
          Cover page: Formation of 3D Self‐Organized Neuron‐Glial Interface Derived from Neural Stem Cells via Mechano‐Electrical Stimulation
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