Researcher(s)
- Erin Smyntek, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Kristi Kiick, Biomedical Engineering, University of Delaware
Abstract
Injectable PEG microgels are three-dimensional cross-linked polymer gel structures that have the potential to be used as delivery vehicles. Microgels are synthesized by combining four-arm PEG thiol with either four-arm PEG vinyl sulfone for four-arm PEG maleimide. A thiol-Michael type addition occurs between these two molecules to form chemically crosslinked microgels. One of the most useful properties of microgels is their ability to hold and release molecules that are encapsulated inside their polymer mesh. Many therapeutics, such as proteins, peptides, and small water-soluble molecules can be encapsulated directly into a microgel’s polymer mesh. Liposomes are another type of cargo molecule that can be encapsulated within microgels. Our chemistry and microgel fabrication methods are unique as they also allow for the chemical incorporation of liposomes which have been used to carry cargo in hydrogel materials in ours and other groups. Liposomes are made up of a bilayer of lipids arranged in a spherical shape and are used as carriers for water-insoluble molecules or small water-soluble molecules. Doxorubicin (Dox) is a prime example of a water-soluble drug that can be encapsulated either freely in a microgel, or within liposomes that are encapsulated in microgels. Its hydrophilic, small, and fluorescent properties make it an ideal molecule for mapping the release of the drug from microgels. Release curves are generated for the release of Dox from liposomes within microgels as well as when Dox is only entrapped by microgels. By encapsulating a drug to be gradually released inside liposomes, rather than entrapping the liposomes inside microgels, it is possible to have more control over the release profile. By characterizing the small molecule release from microgels, the rate of release can be used to draw conclusions about the potential for delivering small molecules from hybrid microgels as a method to improve targeted drug delivery in vasculature. In order to broaden the scope of deliverable molecules, we investigated the ability to load and release DNA via incorporation of polyplexes. Polyplexes are a combination of the hydrophilic, cationic polymer PEI bound to DNA through electrostatic interactions that also have the potential to be encapsulated in microgels. After experimenting with different buffer solutions to make polyplex encapsulated microgels, they were stained and imaged to ensure that the polyplexes are encapsulated correctly. Synthesizing polyplex encapsulated microgels has applications in gene delivery for wound repair as they can be injected directly to the site of the wound and it is possible to target different genes with different populations of microgels.