(534b) Biodegradable Nano-Branched Particles for Sustained Adhesion Andrelease of Drug in Epithelial Tissues

In recent decades, engineered nanoparticles have garnered considerable attention for drug delivery due to their high surface area-to-volume ratios, tunable drug release rates, and ability to deliver drugs to target sites deep within the body. However, weak attractive interactions between nanoparticles and epithelia often result in poor retention times, limiting their benefits in clinical settings. To address this challenge, we present soft microparticles with nanostructured branches that are loaded with hydrophobic drugs. The dendritic morphology of the particles allows them to strongly adhere to epithelial tissues, gradually release drugs, and later degrade into biocompatible products (i.e., lactic acid, glycolic acid) under physiological conditions. We synthesized soft dendritic particles using poly(lactic-co-glycolic acid) (PLGA), a copolymer that is widely used in therapeutic drug delivery applications due to its well-studied biocompatibility and biodegradability. In highly turbulent flows, precipitation of the PLGA in an antisolvent results in the formation of numerous branched nanofibers around the particle, which increases van der Waals forces and enhances the adhesion of particles along soft tissue boundaries. We demonstrate that the adhesive PLGA soft dendritic particle results in stronger surface adhesion than spherical PLGA microparticles using standard tensile testing. We further demonstrate that, due to strong van der Waals forces, the dendritic particles display better retention on epithelial tissues such as a mouse bladders and skin. Finally, we show that sustained release of the FDA-approved chemotherapeutic drug gemcitabine from the dendritic particles effectively kills bladder cancer cells. Our work highlights a novel drug delivery system that offers high retention at target tissues for sustained drug release