Electro-responsive Drug Delivery System Research Articles

Electrically Triggered Drug Delivery from Novel Electrospun Poly(Lactic Acid)/Graphene Oxide/Quercetin Fibrous Scaffolds for Wound Dressing Applications.

The novel controlled and localized delivery of drug molecules to target tissues using an external electric stimulus makes electro-responsive drug delivery systems both feasible and desirable, as well as entailing a reduction in the side effects. Novel micro-scaffold matrices were designed based on poly(lactic acid) (PLA) and graphene oxide (GO) via electrospinning. Quercetin (Q), a natural flavonoid, was loaded into the fiber matrices in order to investigate the potential as a model drug for wound dressing applications. The physico-chemical properties, electrical triggering capacity, antimicrobial assay and biocompatibility were also investigated. The newly fabricated PLA/GO/Q scaffolds showed uniform and smooth surface morphologies, without any beads, and with diameters ranging from 1107 nm (10%PLA/0.1GO/Q) to 1243 nm (10%PLA). The in vitro release tests of Q from the scaffolds showed that Q can be released much faster (up to 8640 times) when an appropriate electric field is applied compared to traditional drug-release approaches. For instance, 10 s of electric stimulation is enough to ensure the full delivery of the loaded Q from the 10%PLA/1%GO/Q microfiber scaffold at both 10 Hz and at 50 Hz. The antimicrobial tests showed the inhibition of bacterial film growth. Certainly, these materials could be loaded with more potent agents for anti-cancer, anti-infection, and anti-osteoporotic therapies. The L929 fibroblast cells cultured on these scaffolds were distributed homogeneously on the scaffolds, and the highest viability value of 82.3% was obtained for the 10%PLA/0.5%GO/Q microfiber scaffold. Moreover, the addition of Q in the PLA/GO matrix stimulated the production of IL-6 at 24 h, which could be linked to an acute inflammatory response in the exposed fibroblast cells, as a potential effect of wound healing. As a general conclusion, these results demonstrate the possibility of developing graphene oxide-based supports for the electrically triggered delivery of biological active agents, with the delivery rate being externally controlled in order to ensure personalized release.

Electroresponsive Alginate-Based Hydrogels for Controlled Release of Hydrophobic Drugs.

Stimuli-responsive biomaterials have attracted significant attention for the construction of on-demand drug release systems. The possibility of using external stimulation to trigger drug release is particularly enticing for hydrophobic compounds, which are not easily released by simple diffusion. In this work, an electrochemically active hydrogel, which has been prepared by gelling a mixture of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and alginate (Alg), has been loaded with curcumin (CUR), a hydrophobic drug with a wide spectrum of clinical applications. The PEDOT/Alg hydrogel is electrochemically active and organizes as segregated PEDOT- and Alg-rich domains, explaining its behavior as an electroresponsive drug delivery system. When loaded with CUR, the hydrogel demonstrates a controlled drug release upon application of a negative electrical voltage. Comparison with the release profiles obtained applying a positive voltage and in the absence of electrical stimuli indicates that the release mechanism dominating this system is complex because of not only the intermolecular interactions between the drug and the polymeric network but also the loading of a hydrophobic drug in a water-containing delivery system.

Biocompatible conductive hydrogels based on dextran and aniline trimer as electro-responsive drug delivery system for localized drug release

Dextran with good biocompatibility and degradability shows great potentials for drug delivery and tissue engineering applications. Electro-responsive drug delivery system can provide on-demand and localized drug release. However, dextran-based conductive hydrogel with electrical stimuli responsiveness as drug delivery system has not been reported. Herein, we designed and fabricated a kind of biocompatible biodegradable conductive hydrogel system with the property of electro-responsiveness as a new smart drug delivery system for localized drug release. These series of hydrogels were synthesized by mixing dextran and electroactive aniline trimer with hexamethylene diisocyanate as crosslinker to form hydrogel network. These series of hydrogels exhibited stable rheological property and controllable swelling ratio. These hydrogels showed good conductivity and desirable electric stimuli ability to control drug release. Furthermore, this kind of hydrogel was controlled by external electrical stimuli to generate a kind of “on-off” precise drug release system. When extra voltage was applied, they released more drug intelligently and less drug molecule without external stimuli. The hydrogel showed good cytocompatibility and in vivo biocompatibility by using H&E staining and Toluidine blue staining. All together, these results indicated that these series of biocompatible conductive dextran-based hydrogels were promising candidates as smart drug delivery systems in future biomedical field.

Electric field-responsive nanoparticles and electric fields: physical, chemical, biological mechanisms and therapeutic prospects.

Electric fields are among physical stimuli that have revolutionized therapy. Occurring endogenously or exogenously, the electric field can be used as a trigger for controlled drug release from electroresponsive drug delivery systems, can stimulate wound healing and cell proliferation, may enhance endocytosis or guide stem cell differentiation. Electric field pulses may be applied to induce cell fusion, can increase the penetration of therapeutic agents into cells, or can be applied as a standalone therapy to ablate tumors. This review describes the main therapeutic trends and overviews the main physical, chemical and biological mechanisms underlying the actions of electric fields. Overall, the electric field can be used in therapeutic approaches in several ways. The electric field can act on drug carriers, cells and tissues. Understanding the multiple effects of this powerful tool will help harnessing its full therapeutic potential in an efficient and safe way.

Carbon Nanohybrids as Electro-Responsive Drug Delivery Systems

Electro-responsive nanomaterials are usually made with polyelectrolytes able to undergo shrinkage or swelling by tuning on electrical fields. Nevertheless, the electrical conductivity of many polymeric materials used for the fabrication of release devices is not high enough to achieve an effective modulation of the drug release. The incorporation of conducting materials (e.g. carbon nanostructures) in polymeric networks has been proposed as a valuable strategy to overcome this limitation. In this regard, carbon nanotubes and graphene, by virtue of their unique chemical structures and attractive physiochemical properties, have been receiving exciting attention primarily in biology and medicine. By their incorporation into composite hydrogels, the biocompatibility and biodegradability of polymers can be merged with the favorable properties of carbon nanostructures, such as enhanced cellular uptake, electromagnetic, and magnetic behavior. The applicability of carbon hybrid materials to modulate release of therapeutics in response to an external current voltage, is being extensively investigated in the present review.

Nano-engineered electro-responsive drug delivery systems.

Stimuli-responsive drug delivery systems can release therapeutic agents when actuated by an appropriate stimulus, whether endogenous or exogenous. Interestingly, exogenous stimuli are completely dissociated from the patient's physiology and can be precisely controlled externally in magnitude, in space, and in time. They can therefore constitute more reproducible means of controlling the release of therapeutics from appropriately responsive delivery systems. One stimulus which has long attracted attention is the application of an electric potential, and most electro-responsive drug delivery systems reported to date have been based on intrinsically conducting polymers. These systems, however, are limited by slow drug release and low drug loading. These challenges are currently driving the development of new electro-responsive delivery systems with higher responsiveness and drug loading, by implementing concepts of nano-engineering into their structure. This review will focus on this exciting and most recent direction taken in this field by first discussing drug delivery from electro-responsive films containing nano-scaled features, and then nanoscale dispersed/colloidal electro-responsive drug delivery systems, such as nanoparticles, micelles, and vesicular structures.

Spherical gelatin/CNTs hybrid microgels as electro-responsive drug delivery systems

Novel spherical hybrid hydrogels composed of gelatin and multi-walled carbon nanotubes were synthesized by emulsion polymerization in the presence of sodium methacrylate and N,N'-ethylenebisacrylamide, and proposed as drug delivery microspheres for the electro-responsive release of Diclofenac sodium salt. Different amounts of nanotubes (up to 35% by weight) were covalently inserted into the polymeric network in order to determine the percentage conferring the highest electric sensitivity to the composite microspheres. Characterization of hydrogels was performed by electrical, morphological and calorimetric analyses, Raman measurements, biocompatibility assays and evaluation of the swelling behaviors in water (pH 1.0 and pH 7.4) with and without the application of an external electric field. Finally, the release profiles were determined and the diffusion behavior was evaluated by semi-empirical equations.

Electroresponsive Polyacrylamide-grafted-xanthan Hydrogels for Drug Delivery

An electroresponsive drug delivery system was developed using poly(acrylamide-grafted-xanthan gum) (PAAm-g-XG) hydrogel for transdermal delivery of ketoprofen. The electrically sensitive PAAm-g-XG copolymer was synthesized by free radical polymerization under nitrogen atmosphere followed by alkaline hydrolysis. When a swollen PAAm-g-XG hydrogel was placed in between a pair of electrodes, deswelling of the hydrogel was observed in the vicinity of electrodes carrying the electric stimulus. The membrane-controlled drug delivery systems were prepared using drug-loaded PAAm-g-XG hydrogel as the reservoir and crosslinked with poly(vinyl alcohol) to form films as rate controlling membranes (RCM). The in vitro drug permeation study from the formulations was performed through excised rat abdominal skin. Drug permeation across the skin was greatly enhanced in the presence of electric stimulus as compared to passive diffusion and was found to be dependent upon the applied electric current strength and crosslink density of RCM. A pulsated pattern of drug release was observed as the electric stimulus was switched `on' and `off.' The skin histopathology study demonstrated that, after the application of an electrical stimulus, there were changes in the structure of stratum corneum and cell structure. These PAAm-g-XG hydrogel could be useful as transdermal drug delivery systems actuated by an electric signal to provide on-demand release of drugs.