Recent advances in CO2 bubble-generating carrier systems for localized controlled release

Abstract

This article reviews recent progress in the development of carbon dioxide (CO₂) bubble-generating drug carriers, including their designs and operating mechanisms; these carriers constitute an advanced class of stimuli-responsive delivery systems with considerable potential. The drug carriers contain stimuli-responsive agents, which are stable before they reach the target location, but enable rapid drug release that is triggered by the generation of CO₂ bubbles, which are chemically inert, under certain stimuli. These CO₂ bubble-generating carrier systems can be used to accumulate locally a delivered drug at the diseased tissue, while reducing side effects on the normal tissue, improving their therapeutic effectiveness. Since the generated CO₂ bubbles are hyperechogenic, they may also be used as an ultrasound contrast agent in elucidating the status of the carriers and providing real-time diagnostic images. Perspectives of the future of applications of gases with therapeutic effects, such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S), in such bubble-generating carrier systems, are also briefly discussed.

Keywords: Ammonium bicarbonate; Calcium carbonate; Gas bubble; Sodium bicarbonate; Stimuli-responsiveness.