RUI: Boronic Ester Modified Polysaccharides for Oxidation-Responsive Delivery Applications

Mount Holyoke College, South Hadley MA

Investigators

Abstract

Non-technical summary: The field of drug delivery aims to improve or control how bioactive molecules get to their intended target. This is most often accomplished using carrier "vehicles" that are designed to locally release their payload at a desired time, rate, and location, often in response to a specific signal molecule. Hydrogen peroxide is an oxidizing agent that is frequently used as this signal molecule because it is generated as a part of the immune response and in ischemic events like heart attacks and strokes. Boronic esters are chemical groups used to give materials sensitivity to hydrogen peroxide; this research investigates the effects of making changes to the molecular structure surrounding these boronic esters. The PI synthesizes new materials by modifying biologically derived polymers with a range of boronic esters, and then we measure whether and how those modifications lead to materials capable of carrying payload molecules and releasing them in response to oxidizing environments. This research aims to discover design parameters that might be used to make the next generation of drug delivery vehicles. Mount Holyoke College is the oldest women's college in the US, and serves a diverse student body. The students who engage in this research will learn modern laboratory techniques and scientific communication skills, and their experiences will prepare them for future endeavors in a wide variety of fields. Technical summary: The use of arylboronic esters to endow molecular sensors and delivery vehicles with sensitivity to hydrogen peroxides has become widespread in the past 15 years. The large majority of these contain pinacol (2,3-dimethylbutane-2,3-diol) as the esterifying group. The identity of this diol influences the rate of degradation in response to hydrogen peroxide, and may additionally affect the interactions between boronic esters and biomolecules. This project will explore the effects replacing this group with more rigid or sterically hindered diols in the context of modified polysaccharide-based polymeric materials. These materials will be evaluated based on their solution-processability, hydrolytic stability, and sensitivity to hydrogen peroxide. Additionally, esterifying diols will be modified with hydrophobicity-modulating groups or releasable bioactive molecules, and their ability to encapsulate and release molecular payloads will be evaluated. This research will result in improved understanding of the design parameters for boronic ester-containing molecules and materials. Mount Holyoke College is the oldest women?s college in the US, and serves a diverse student body. The students that engage in this research will learn modern laboratory techniques, scientific communication skills, and their experiences will prepare them for future endeavors in a wide variety of fields. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.