Alchemistic Polymers for the Delivery of Therapeutic Agents in Treatment of Pediatric Tracheomalacia




Goodfriend, Amy Claire

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Tracheomalacia is characterized by flaccidity of the airway whereby tracheal collapse occurs during respiration. Globally, approximately 1:21 children are affected by airway malacia whether it be acquired or from congenital origins. Of the available modalities of treatment, stenting has the greatest potential for success but remains controversial in pediatrics due to limitations in biocompatibility and internal reinforcement. There is a pressing need in the design of bioresorbable devices for the treatment of this disease. Ergo, this research shows the development of a MRI-visible multi-drug release composite coating that is to be applied to a bioresorbable stent. The coating combines novel polymers synthesized using non-traditional initiators such as contrast medium and therapeutic agents. The characterization of these polymers leads to the optimization of a coating platform. Using a factorial design, a library of drug delivery particles for the delivery of an anti-inflammatory agent was generated. The novel polymer containing the contrast agent was blended with preexisting polymers to formulate theranostic nanoparticles for a three month delivery of an anti-inflammatory agent. The optimized polymer platform is synthesized using a contrast medium and an antibiotic to inhibit bacterial infection up to two weeks. Thus the combination of the polymeric theranostic nanoparticles and the antibiotic release polymer platform were combined to generate a composite coating. Each individual component of the composite coating and the combination of components was analyzed for biocompatibility and therapeutic potential in-vitro. The local multi-drug delivery and imaging capabilities in this coating design in combination with a bioresorbable stent should result in a successful intervention specifically designed for pediatric tracheomalacia. This design should mitigate long-term risks associated with current permanent devices and provide necessary theranostic agents to facilitate healing and monitor progress via non-invasive imaging techniques.

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