A signal-responsive hydrogel for controlled drug release

Open Access
Author:
Huang, Yike
Graduate Program:
Bioengineering
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
July 02, 2015
Committee Members:
  • Yong Wang, Thesis Advisor
Keywords:
  • drug delivery
  • controlled protein release
  • signal responsive material
  • aptamer
Abstract:
Precisely controlling the release of pharmaceutical compounds is necessary in order to achieve maximum therapeutic benefit. Controlled drug release systems of different sizes, shapes, structures, and functionalities have been widely investigated for drug delivery and tissue engineering applications. The most promising drug release systems are on-demand release systems in which drugs are released in response to environmental stimuli, traditionally through dramatic physical or chemical changes of the carrier material. In particular, self-regulated drug release systems, which respond to changes in the concentration of specific analytes, are especially intriguing as the systems can be applied to maintain homeostasis by counteracting pathological events as they occur. Though current techniques to engineer self-regulated systems show promise, they are not generalizable for complex pathological situations where numerous signals are present. Hence, a dual aptamer-based hydrogel system that is potentially able to respond to any specific signal molecule was engineered. The dual aptamer system includes a drug-loading oligonucleotide strand and a signal molecule-binding strand. In the absence of the signal molecule, the two strands are hybridized and the system sequesters the drug. In the presence of the signal molecule, the two strands separate and the system releases the drug. In the thesis, human vascular endothelial growth factor (VEGF) and adenosine were used as the model drug and signal molecule, respectively. First, the drug-loading strand was designed and its activated and deactivated states were optimized for VEGF sequestration and release. Then, the signal molecule-binding strand was generated and the association and dissociation of the two strands in response to adenosine investigated. Finally, the dual aptamer-based superporous hydrogel system was established and the behavior of adenosine-triggered VEGF release was characterized.