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Helen Chuang Chemical Engineering Grad Student |
I was born and raised in Taiwan and came to the U.S. for high school and college, spending eight sunny years in California. I obtained my B.S. in chemical engineering from Caltech. I enjoy transferring my laboratory skills home by experimenting on ways of preparing food, using my husband as the lab rat. For stress relief from failed research, I enjoy jogging outdoors or a trip to the gym.
My research involves multilayered polymer thin films that are constructed via the layer-by-layer (LbL) deposition technique using a unique water-hydrolyzable polycation, resulting in coatings that are stable in air but erode top-down in a layer-by-layer fashion when exposed to aqueous physiological environment. The multilayered nature of these films allows for the encapsulations and subsequent sequential releases of multiple drugs, with individually tunable dosage and timing (Figure 1). These films are nm-thin, very shape conformal, and can be deposited onto virtually any material. In addition, the fabrication process is cheap, easily scalable, and involves only mild aqueous solutions, making it ideal for encapsulating sensitive biologic drugs.
Our target application is orthopedic implant coatings that can address the multiple complications of pain, infection, and implant rejection through the sequential releases of pain killers + anti-inflammatory agents, antibiotics, and growth factors (Figure 1). My research focuses on the antibiotic component of this coating. I have successfully encapsulated several classes of antibiotics with a wide range of in vitro activity (Figure 2), encapsulation dosage, and release rate. Other therapeutics for the orthopedic implant coating are being investigated by Mara Macdonald (growth factors) and Renee Smith (anti-inflammatory).
Current foci of my project are sustained multi-day release of novel antibiotics and in vivo evaluation of efficacy and biocompatibility through osteomyelitis (bone infection) models in rabbits (Figure 3).
Other projects that I’ve been involved with include (1) the sequential release of multiple distinct polysaccharides, (2) the encapsulation of antibiotics, an anti-coagulant, and an enzyme at therapeutically relevant dosages, with established controls over the release rate and dosage of these drugs and in vitro activity, and (3) encapsulation and controlled release of siRNAs. Other LbL drug delivery projects in our lab include wound dressings for battlefield application (Anita Shukla) and electrochemically-activated thin films (Daniel Schmidt).
Aside from drug-eluting coatings on biomedical devices, this technology can also be applied towards the delivery of a single therapeutic agent with a complex release profile, such as a self-scheduling vaccine. Such a timing-controlled coating can be deposited onto nanospheres for intravenous administration. Applications are not limited to biomedical uses; other possibilities include coated ‘SuperSeeds’ that can elute their own schedule of fertilizers and pesticides, or coated laundry beads that schedule their own release of detergent, bleach, fragrance, and softeners.
Figure 1. Schematic of proposed therapeutic coating on orthopedic implants, demonstrating the sequential releases of pain killers, antibiotics, then growth factors as the coating erodes controllably top-down. The bottom graphs show the proposed timescale of release for each therapeutic agent.
Figure 2. A sample set of Kirby-Bauer disk diffusion assays demonstrating the ability of our antimicrobial films in inhibiting the growth of Staphylococcus aureus, a bacterial species responsible for many biomedical device infections. (Left) a control plate of S. Aureus culture with no film placed on it, showing complete coverage by S. Aureus culture, (Center) a plated S. Aureus culture with our antimicrobial film placed at the center, showing a ‘zone of inhibition’ in which no growth occurred, and (Right) a plated S. Aureus culture with another antimicrobial film of higher antibiotic loading, showing an even bigger zone of inhibition.
Figure 3. In vivo evaluation of antibiotic coating involves establishing osteomyelitis (bone infection) within a cylindrical defect drilled into the medial femoral condyle (i.e. right above the knee joint on the interior side), then treating the infection by press-fitting a coated cylindrical implant into the defect.
