Temperature Responsive Drug Delivery Systems by Combining Nanoparticles and Flexible Devices

Abstract

Recently, nanoparticles have been investigated for their applications to biomedical areas including diagnosis, therapy and theranostics. Controlled drug release systems with internal/external stimuli can provide the effective therapeutic functions on targeted region. Among stimuli-responsive drug delivery, temperature-responsive drug delivery enables on/off, step-wised, and multi-stage drug delivery with controlled heating. With integration of flexible devices, temperature-responsive drug delivery can make considerable progress such as precise control of temperature, multi-stage delivery, and wireless control system. Firstly, temperature-responsive microneedles were fabricated with introducing phase change material (PCM) to the conventional microneedle system. To utilize phase change material as drug carriers, I successfully synthesized phase change nanoparticles (PCNs) with probe-ultrasonicating process. Using different PCMs, I could control the temperature of drug releasing at 40 and 45 oC, respectively. The phase change nanoparticles (PCNs) could load the type 2 diabetes drug (metformin) and only release the drugs when they are heated above melting temperatures. By integrating with three channel heaters and temperature sensors, microneedles enable multi-stage drug delivery upto six releasing amounts for diabetes treatment. Secondly, theranostic nanoparticles were developed by coating of temperature-responsive polymers with photo- and chemo-drugs for colon cancer treatment. By integrating lasers with endoscope system, I could overcome penetration depth problem of lasers. With irradiation of near-infrared (NIR) laser, Au nanorods generate heat, which can function as photothermal therapy and activate temperature-responsive delivery of doxorubicin. Also, photodynamic dyes on mesoporous silica shells can act as both imaging and therapeutic agents with red laser. These combined therapies (photothermal, photodynamic, and chemotherapy) made synergistic effect of colon cancer treatment in in-vitro and in-vivo experiments. The nanoparticles can actively deliver to colon cancer cells by conjugated antibodies and selectively treat cancer cells with irradiation of red/NIR lasers, which reduces side effects of cancer therapy.