Development of a novel nanogel for non-invasive transdermal delivery of cancer vaccines using hyaluronic acid
Mentor: Omid Farokhzad, M.D. (Brigham and Women's Hospital)
Drug administration via needle injection requires specialized personnel, causes patient discomfort form the needle, and serves as a potential site of infection. With the advent of nanomedicine, noninvasive drug delivery routes are capable of providing the same efficacy while increasing patient compliancy, comfort and decreasing biohazardous waste. Skin is the first line of defense, preventing pathogens from entering the body by a complex immune system. The efficacy of previously explored topical and transdermal drugs have fallen short in comparison to their injected counterparts due to this significant skin barrier. Hyaluronic acid (HA) is a biocompatible, biodegradable, non-toxic and naturally occurring polysaccharide with a hydrophobic patch domain. As HA binds to its receptors in each skin layer, it is broken down into smaller fragments causing the drug carried to be released. Blood and lymphatic vessels located in the dermis layer will absorb the nanoparticle-carrying drug, allowing for a systemic along with a local effect. In this work, a novel nanogel and drug delivery system is formed using HA with “click” chemistry crosslinkers. The nanogel system is optimized by varying the concentrations of each crosslinker and testing each sample via DLS and TEM to determine the size. The free functional group and amphiphilic nature of HA enable the conjugation and encapsulation of several drugs, such as vaccines and anti-inflammatory agents. The proof of concept for each application will be tested via in vitro analysis using keratinocyte cell lines. In vivo studies will consist of bioimaging to specifically track nanoparticle activity and method of action. This nanogel system can be exploited to treat various diseases without needle injection.
Unpublished electron microscopy image of hyaluronic acid nanoparticles. The schematic illustrates the “click” chemistry reaction between tetrazine (Tz) and trans-cyclooctene (TCO) used to crosslink the polymeric particles. Source: