Self-propelled PLGA micromotor with chemotactic response to inflammation

Local drug delivery systems have recently been developed for multiple diseases that have the requirements of site-specific actions, prolonged delivery periods, and decreased drug dosage to reduce undesirable side effects. The challenge for such systems is to achieve directional and precise delivery in inaccessible narrow lesions, such as periodontal pockets or root canals in deeper portions of the dentinal tubules. The primary strategy to tackle this challenge is fabricating a smart tracking delivery system. Here, drug-loaded biodegradable micromotors showing self-propelled directional movement along a hydrogen peroxide concentration gradient produced by phorbol esters-stimulated macrophages are reported. The drug-loaded poly(lactic-co-glycolic acid) micromotors with asymmetric coverage of enzyme (patch-like enzyme distribution) are prepared by electrospraying and postfunctionalized with catalase via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide coupling. Doxycycline, a common drug for the treatment of periodontal disease, is selected as a model drug, and the release study by high-performance liquid chromatography is shown that both the postfunctionalization step and the presence of hydrogen peroxide have no negative influence on drug release profiles. The movement behavior in the presence of hydrogen peroxide is confirmed by nanoparticle tracking analysis. An in vitro model is designed and confirmed the response efficiency and directional control of the micromotors toward phorbol esters-stimulated macrophages.