A systematic correlation of nanoparticle size with diffusivity through biological fluids

Nanomedicine, the application of nanotechnology for medical purposes, has been widely identified as a potential solution for today‟s healthcare problems. Nanomedicine uses the "bottom-up‟ principles of nanoscale engineering to improve areas of medicine which have previously been considered undevelopable. One of the enduring challenges for medicine is the design of innovative devices able to overcome biological barriers, allowing drugs and therapeutics to effectively reach their correct location of action. Biological barriers are a defence mechanism of the body which are extremely well-evolved to protect the body from foreign and harmful particles. Therapeutic drugs and devices, which are not harmful, are often identified by the body as dangerous because their composition differs from native and accepted entities. The traversal of these biological barriers, such as mucus, remains a bottleneck in the progress of drug delivery and gene therapy. The mucus barrier physically limits the motion of particles due to its complicated mesh structure which obstructs the particles' traversal path. Mucus fibres can also adhere to the particles, entrapping them and restricting their motion. Particle traversal of mucus is carried out by passive diffusion. As diffusion has traditionally been defined by the Stokes-Einstein equation as inversely proportional to particle radius, it follows that reducing particle sizes into the nanoscale would result in increased diffusive ability. These predictions, however, do not consider the obstructive effects of the complicated mesh structure for the case of mucus. The exact effect of reducing particle size into the nanoscale for diffusion through mucus is therefore unknown. Multiple Particle Tracking was used to obtain real-time movies of the diffusion of nanoparticles, ranging from 12nm – 220nm in diameter, through mucus samples. The experimental data generated was used to systematically correlate the relationship between particle size and diffusivity through mucus. This study reveals that nanoparticles, smaller than the average pore size in the mucus mesh structure, can diffuse through lower viscosity pores which pose less resistance to diffusive motion, allowing nanoparticles to travel at up to four times the speed expected from the bulk viscosity of the mucus. This type of information can help researchers understand the importance of size for therapeutic nanoparticles, allowing researchers to decide whether attempts to decrease nanoparticle size at the expense of other functionality are worthwhile.EThOS - Electronic Theses Online ServiceGBUnited Kingdo