Non-porous silica nanoparticles as a cavitation sensitive vehicle for antibiotic delivery

Abstract

Ultrasound stimulated drug delivery is attractive for controlled dose and localised delivery to reduce excess loss of drug and side effects, which for antibiotics is pertinent to the fight against antimicrobial resistance. Low frequency ultrasound is commonly used in dental clinical practice for bacterial biofilm removal and is an attractive versatile stimulus for drug release. Here we introduce nonporous (amorphous) silica nanoparticles as a biocompatible, encapsulant for triggered drug release by low frequency ultrasound. A 20 kHz ultrasonic sonotrode is used in to evaluate the release of the antibiotic ciprofloxacin, CPX, from non-porous particles, CPX ⊂ SiO₂. Laser doppler vibrometry (LDV) was employed to characterise the ultrasonic vibration displacement of the sonotrode. Drug release from CPX ⊂ SiO₂ was monitored for increasing the tip displacement. Clinically relevant quantities of CPX release (5.7 mg/L) occurred at 40 μm tip displacement in our studies. A strong correlation was observed between cavitation features in the acoustic spectra and drug release from CPX ⊂ SiO₂. Silica nanoparticles with and without encapsulated CPX, CPX ⊂ SiO₂ and SiO₂, respectively, were found to promote cavitation at lower amplitudes confirmed by high-speed imaging, in contrast to mesoporous particles with and without adsorbed CPX, CPX@m-SiO₂ and m-SiO₂. Spectra of the emissions collected via an acoustic cavitation detector supported these results. Our studies demonstrate a novel platform for drug delivery employing low frequency ultrasound for synergistic enhancement of cavitation effects and triggered drug release.