BME MS Thesis Defense Seminar: Benyamin Horev
Thursday, April 10, 2014
Goergen Hall 101 (Sloan Auditorium)
"pH-Activated Nanoparticles for Targeted Delivery and Controlled Release of Bioactive Agents to Disrupt Oral Biofilms"
Advisor: Danielle Benoit
The cost to treat or prevent oral biofilm-related infectious diseases exceeds $81 billion annually in the US alone. The development of effective therapies to control oral biofilm formation is challenging, as topically-introduced antibacterial agents must target the biofilm microenvironment while avoiding rapid clearance from the biofilm-tooth interface. Therefore, we developed nanoparticle carriers (NPC) capable of binding to tooth-pellicle and biofilm exopolysacharide (EPS) matrix that respond to acidic pH microenvironments within cariogenic biofilms by rapidly releasing drug. NPC are formed of diblock copolymers composed of dimethylaminoethyl methacrylate (DMAEMA), butyl methacrylate (BMA), and 2-propylacrylic acid (PAA) (p(DMAEMA)-b-p(DMAEMA-co-BMA-co-PAA)). Diblocks self-assemble into cationic micelles that exhibit electrostatic interactions to anionic tooth and biofilm matrix, resulting in high binding affinities. Moreover, and owing to hydrophobic and pH-responsive cores, NPC load high amounts of hydrophobic drug, farnesol, and exhibit pH-responsive behaviors that result in core destabilization at acidic pH, which are characteristic of biofilm microenvironments. Specifically, farnesol release was pH-dependent with 2-folds more rapid drug release at pH 4.5 compared to physiologic pH 7.2. Topical applications of farnesol-loaded NPC reduced the number of viable cells within Streptococcus mutans (S. mutans) biofilms to ˜50%, and resulted in ˜2-fold greater biofilm removal from pellicle surfaces when exposed to shear stress, compared to free farnesol or no treatment controls. Overall, NPC have great potential to enhance antibacterial drug efficacy through targeted delivery and controlled drug release in response to microenvironmental pH triggers, and represent a promising method to effectively treat biofilm-related dental diseases.