Nanoparticles are a promising solution for delivery of a wide range of medicines and vaccines. Optimizing their design depends on being able to resolve, understand, and predict biophysical and therapeutic properties, as a function of design parameters. While existing tools have made great progress, gaps in understanding remain because of the inability to make detailed measurements of multiple correlated properties. Typically, an average measurement is made across a heterogeneous population, obscuring potentially important information. In this work, we develop and apply a method for characterizing nanoparticles with single-particle resolution. We use convex lens-induced confinement (CLiC) microscopy to isolate and quantify the diffusive trajectories and fluorescent intensities of individual nanoparticles trapped in microwells for long times. First, we benchmark detailed measurements of fluorescent polystyrene nanoparticles against prior data to validate our approach. Second, we apply our method to investigate the size and loading properties of lipid nanoparticle (LNP) vehicles containing silencing RNA (siRNA), as a function of lipid formulation, solution pH, and drug-loading. By taking a comprehensive look at the correlation between the intensity and size measurements, we gain insights into LNP structure and how the siRNA is distributed in the LNP. Beyond introducing an analytic for size and loading, this work allows for future studies of dynamics with single-particle resolution, such as LNP fusion and drug-release kinetics. The prime contribution of this work is to better understand the connections between microscopic and macroscopic properties of drug-delivery vehicles, enabling and accelerating their discovery and development.

A drug delivery system which contains antibiotics for treating osteomyelitis based on a borate bioactive glass was developed. The system was consisted of the borate bioactive glass6Na2O-8K2O-8MgO-22CaO-54B2O3-2P2O5(mol%) as the solid phase, the solution of chitosan, critic acid and glucose as the liquid phase and carried watersoluble teicoplanin as the antibiotics. In vitro test, the drug release behavior, the mechanical properties and the biocompatibility of the drug delivery system were investigated, when the drug delivery device was immersed in phosphate buffer solution (PBS). The drug concentration in PBS were tested by HPLC(High Performance Liquid Chromatography). The drug releasing process could last as long as 30d and 72% of the drug content was released within the first week. The mechanism for the drug releasing from the devices was in accordance with Fick’s diffusion law, when the process was simulated in the Peppas model. The XRD results proved that the bioactive glass material converted into hydroapatite (HA) during the drug release process, indicating that the system had bioactivity in vitro. In vivo test on rabbits, the drug delivery system cured the osteomyelitis in tibial bone, and stimulated the regeneration of tibial bone. The above results proved that the borate bioactive glass was a suitable material for carrying antibiotics to cure osteomyelitis, and for stimulating bone regeneration