Mucoadhesive Nanoparticles for Treatment of Influenza A

Abstract

Influenza A is the most pandemic-prone class of the influenza virus, with new strains emerging every year. Though vaccination is promoted as the vanguard against wide-spread infection, it is not enough to withstand mutating virus strains. Current antiviral therapeutics are frequently falling to resistant virus types. Better antiviral therapies are needed, and nanotechnology can be part of the solution. Mucoadhesive nanoparticles (MNPs) are nanoparticles which bind to the mucus membrane. Polymeric micellar MNPs made from poly(lactic acid), dextran, and phenylboronic acid have been quite successful in ocular drug delivery to treat dry-eye disease. Their mucus-binding ability points to applications in treatments for other diseases which target the mucus membrane, such as influenza A. This thesis aims to determine the potential for MNPs as a new class of antiviral therapeutic. A review of current literature highlights the use of nanoparticles in influenza treatment, and the work in this thesis draws on this information. Binding kinetics studies are conducted to determine the strength of MNPs’ binding with mucin/sialic acid, and compare this to that of sialic acid-influenza as found in literature. The effect of aerosolization on the MNPs is studied in terms of their key characteristics such as morphology and drug encapsulation in order to determine their suitability as a delivery vehicle to the pulmonary tract. The binding kinetics studies also provide another avenue of study regarding prediction of in vivo mucoadhesion using in vitro techniques. Overall these studies present a promising basis for the use of MNPs as a novel antiviral therapeutic. Through detailed binding kinetics and aerosolization studies, the first in vitro steps have been established for their viable use. Further steps involving in vitro and in vivo studies are discussed in the conclusions.