Fabrication and characterization of 2 dimensional biodegradable microrobot with 5 Fluorouracil for targeted drug delivery

Abstract

Microrobots for biomedical applications have various advantages such as minimally invasive surgery, targeted delivery of drug or biological compounds to specific area, as well as transportation energies, for example, thermal energy by hyperthermia treatment in comparison to a conventional invasive surgery. For such targeted therapeutics with microrobots, it is crucial not only to accurately control them but also to make them biocompatible to use in an in-vivo environment. In terms of the biocompatibility, biodegradable material has emerged as a promising material because it naturally biodegrades into harmless substances in aqueous environment therefore the microrobot does not need to be retrieved from the body. In this thesis, we developed 2 dimensional biodegradable microrobot for targeted drug delivery that consists of poly (D,L-lactide-co-glycolide acid) (PLGA), magnetic particles (Fe particles) (average size < 10 μm) and a drug compound, 5 Fluorouracil (5-FU). The microrobot was fabricated with various 2 dimensional shapes of water-dissoluble PVA templates cut by using UV laser micro machining. Most biomedical microrobots that uses photo-curable reagent to polymerize and form microrobot structure under UV require post-process to load drugs because drugs can be denatured by UV. In contrast, the developed biodegradable microrobot allows simultaneous encapsulation of anticancer drug (5-FU) without additional drug loading procedure, forming a microrobot structure in PLGA/Fe/5-FU solution. Translational and rotational motion of the developed 2 dimensional biodegradable microrobot were remotely and accurately controlled by external magnetic field (constant magnetic field (B) to Z axis and magnetic field gradient (∇B) to X axis) manipulated using an electromagnetic actuation (EMA) system. The fastest translational velocity of fabricated microrobot with 60 % (w/v) of magnetic particles was approximately 2.8 mm/s (≈1/5 body length per second). They have successfully loaded and released approximately 0.013 μg/microrobot of anticancer drug (5-FU) in aqueous environment (around pH 7, 37 ˚C) by biodegrading itself for 6 weeks. In conclusion, the facile fabrication was developed to form 2 dimensional biodegradable microrobot with various shapes using UV laser micro machining, encapsulating drugs into the microrobot simultaneously. The 2 dimensional biodegradable microrobot was successfully controlled by using electromagnetic actuation (EMA) system and released drugs for 6 weeks by biodegrading itself. ⓒ 2017 DGIST