Development of a Light Actuated Drug Delivery-on-Demand System
- Author(s): Linsley, Chase Schilling
- Advisor(s): Wu, Benjamin M
- et al.
The need for temporal-spatial control over the release of biologically active molecules has motivated efforts to engineer novel drug delivery-on-demand strategies actuated via light irradiation. Many systems, however, have been limited to in vitro proof-of-concept due to biocompatibility issues with the photo-responsive moieties or the light wavelength, intensity and duration. To overcome these limitations, the objective of this dissertation was to design a light actuated drug delivery-on-demand strategy that uses biocompatible chromophores and safe wavelengths of light, thereby advancing the clinical prospects of light actuated drug delivery-on-demand systems. This was achieved by 1) characterizing the photothermal response of biocompatible visible light and near infrared-responsive chromophores, and demonstrating the feasibility and functionality of the light actuated on-demand drug delivery system in vitro; and 2) designing a modular drug delivery-on-demand system that could control the release of biologically active molecules over an extended period of time.
Three biocompatible chromophores - cardiogreen, methylene blue, and riboflavin - were identified and demonstrated significant photothermal response upon exposure to near infrared and visible light, and the amount of temperature change was dependent upon light intensity, wavelength as well as chromophore concentration. As a proof-of-concept, pulsatile release of a model protein from a thermally responsive delivery vehicle fabricated from poly (N-isopropylacrylamide) was achieved over four days by loading the delivery vehicle with cardiogreen and irradiating with near infrared light. To extend the useful lifetime of the light actuated drug delivery-on-demand system, a modular, reservoir-valve system was designed. Using poly (ethylene glycol) as a reservoir for model small molecule drugs combined with a poly (N-isopropylacrylamide) valve spiked with chromophore-loaded liposomes, pulsatile release was achieved over seven days upon light irradiation. Ultimately, this drug delivery strategy has potential for clinical applications that require explicit control over the presentation of biologically active molecules. Further research into the design and fabrication of novel biocompatible thermally responsive delivery vehicles will aid in the advancement of the light actuated drug delivery-on-demand strategy described here.