Mucus barrier components, challenges for nanoscale drug delivery
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In this present study changes in nanoparticles motion were explored in the presence and the absence of G-blocks in mucus matrices such as; porcine gastric mucus (45 mg/ml), and a mixture of porcine gastric mucus + polymeric mucus (non degraded mucin from porcine stomach (45 mg/ml) respectively.These mucus types were tested to determine nanoparticle motion in their mesh networks, in order to deepen the understanding of nanoparticle motion behaviors in these complex biological environments, clarify the involvement of mucus components as motion barrier to nanoparticle diffusion, as well as identify the exciting challenges for nanoscale drug delivery.Multiple particle tracking technique was used to image movements of amine and carboxylate modified nanoparticles in mucus samples precisely by a series of experimental design. Nanoparticles exhibited sub diffusive motion in mucus samples, which is a common behavior of nanoparticle in mucus matrix, however, there were other types of nanoparticle motion modes seen in samples; diffusive (nanoparticle display increased motion with time scale), immobile (nanoparticle would not move with time scale), and hindered motion (nanoparticle would not move further in mucus with time scale and show vibrating motion).It was found that, nanoparticle motion is dependent on mucus components present in mucus mesh. A significant increased on nanoparticle motion was identified in porcine gastric mucus mixed with polymeric mucus (45 mg/ml) compared to nanoparticle motion in sigma porcine mucus which not subjected to mixture with polymeric mucus (45 mg/ml).It was stated that, polymeric mucus makes more pores or either provides a scaffold in mucus network which results in increased nanoparticle motion. A shift toward greater nanoparticle motion at longer time scales confirmed the ability of G-blocks to improve nanoparticle diffusion. It is apparent that high levels of G-blocks may collapse all the structure and increase the mucus barrier. In addition, nanoparticle motion is dependent on the surface chemistry which determines the degree of interaction with the mucus components and mucus barrier disruption. The apparent barriers to particle motion vary with time scale. At short timescales movements on short distance are shown.Trajectory patterns at short time scales could reflect particle interaction with the matrix architecture or moving within network pores but are unlikely to show particles crossing matrix pore elements.A key success in nanoparticle transport is to avoid adhesive interaction within mucus components. Results of this study indicate that, G-blocks have enough potential to engineer nanoparticle in order to traverse mucus matrix and reach targeted sites in the body.Reduction of barrier properties of the mucus layer would be associated to G-blocks ability to alter mucus rheology in a favorable manner to uptake nanoparticle.Whether the barrier is decresed or increased by G-blocks depends on amount of G-blocks, Nanoparticle surface, addition of G-blocks in mucus matrix, as well as time scale.Such an improvement in nanoparticle transport through mucus blanket can lead to innovative drug delivery system for site specific target drug release, in order to combat against respiratory disease in particular cystic fibrosis disorder.The data presented here may be consistant with a model where G-blocks alter the mucus barrier architecture. This study must be repeated in ex vivo native matricses because it has been clearly shown here that the matrix components is critical to the barrier properties.