Ultrasonic/electrical dual stimulation response nanocomposite bioelectret for controlled precision drug release

Abstract

Electret materials have attracted extensive attention because of their permanent polarization and electrostatic effect. However, it is one of problem that needs to be solved in biological application to manipulate the change of surface charge of electret by external stimulation. In this work, a drug-loaded electret with flexibility and no cytotoxicity was prepared under relatively mild conditions. The electret can release the charge through stress change and ultrasonic stimulation, and the drug release can be accurately controlled with the help of ultrasonic and electric double stimulation response. Here, the dipoles like particles of carnauba wax nanoparticles (nCW) are fixed in the matrix based on the interpenetrating polymer network structure, and "frozen" oriented dipolar particles that are treated by thermal polarization and cooled at high field strength. Subsequently, the charge density of the prepared composite electret can reach 101.1 ​nC/m² at the initial stage of polarization and 21.1 ​nC/m² after 3 weeks. In addition, the stimulated change of electret surface charge flow under cyclic tensile stress and cyclic compressive stress can generate a current of 0.187 ​nA and 0.105 ​nA at most. The ultrasonic stimulation results show that when the ultrasonic emission power was 90% (P_max ​= ​1200 ​W), the current of 0.472 ​nA can be generated. Finally, the drug release characteristics and biocompatibility of the nCW composite electret containing curcumin were tested. The results showed that it not only had the ability to accurately control the release by ultrasound, but also triggered the electrical effect of the material. The prepared drug loaded composite bioelectret provides a new way for the construction, design and testing of the bioelectret. Its ultrasonic and electrical double stimulation response can be accurately controlled and released as required, and it has broad application prospects.

Keywords: Charge density; Double stimulation response; Drug release; Flexible bioelectret.

Graphical abstract

Fig. 1

Preparation of DN-gel@nCW flexible bioelectret. (a) The synthetic scheme of DN-gel@nCW composites. (b) Polarization of DN-gel@nCW flexible bioelectret.

Fig. 2

(a) Preparation of carnauba wax microcapsule. The particle size and zeta potential of (b) nCW-1, (c) nCW-2, (d) nCW-3, (e) nCW-4, and (f) nCW-5 respectively. (g) The SEM microscopic image of the morphology of nCW.

Fig. 3

Characterization for DN-gel composites. (a) Macroscopic, microscopic SEM images and EDS, (b) FTIR, (c) XRD, (d) The water holding ratio, (e) Contact angle (f) Tensile stress-strain curve and (g) Compression stress-strain curve, (h) Young's modulus and Compression modulus of DN-gel-1, DN-gel-2, DN-gel-3, DN-gel-4, and DN-gel-3@nCW composite.

Fig. 4

Poling characteristics. (a) Diagram of breakdown test device for composite gels and breakdown voltage for different composite gels. (b) Schematic diagram of surface charge density measurement. When the upper plate is near or away from the film, the charge is captured and passed through a charge amplifier connected to the upper and lower electrodes. (c) Charge density of pDN-gel-3 and pDN-gel-3@nCW at different polarization temperatures under 200 ​kV/m. (d) Charge density of different pDN-gel composites after polarization, data is obtained after 24h test. (e) Charge attenuation of different pDN-gel composites. (f) Dielectric constant (solid lines) and dielectric loss (dashed lines) of nCW, DN-gel-3, and DN-gel-3@nCW as a function of frequency at room temperature. (g) Schematic diagram of a thermal polarization-oriented freezing dipole. (h) Polarization charge distribution and charge conduction mechanism in pDN-gel flexible bioelectret.

Fig. 5

External stimuli control mechanical and electrical conduction of the flexible bioelectret. Schematic diagram of electret surface charge test device (a) under stretch and (d) under compression. Electret surface charge of (b) unpolarized and (c) polarized DN-gel-3@nCW at different stretching frequencies. Electret surface charge of (e) unpolarized and (f) polarized DN-gel-3@nCW at different compression frequencies. Linear fit to charge change of pDN-gel-3@nCW under (g) stretching or (h) compression conditions. (i) Output current as a function of the frequency of stretching or compression.

Fig. 6

Electric power generation by ultrasound propagation in pDN-gel-3@nCW. (a) Schematic diagram of ultrasonic stimulation electromechanical conduction device and the effect of ultrasonic on shear and longitudinal waves generated by pDN-gel-3@nCW. (b) Effect of different ultrasonic power on surface charge of unpolarized and polarized DN-gel-3@nCW. (c) The charge change rate and (d) output current as a function of ultrasonic power.

Fig. 7

Ultrasonic/electrical dual stimulation response for controlled drug release. (a) Cumulative release curve and (b) Cur release rate curve of drug-loaded membrane at different time points. (c) Cumulative release curve and (d) Cur release rate curve of drug-loaded membrane at different ultrasonic treatment time points. (e) Mechanism of accelerating Cur release from drug-loaded membranes by ultrasonic treatment.

Fig. 8

Biocompatibility properties. (a) Calcein AM staining for live cells. Results of CCK-8 assay: OD values (b) and cell viability (c). ∗P ​< ​0.05 compared with blank control, ∗∗P ​< ​0.01 compared with blank control.