Mucus-penetrating nanoparticles made with "mucoadhesive" poly(vinyl alcohol)

Nanoparticles that readily penetrate mucosal layers are desirable for a variety of biomedical applications. Nevertheless, most nanoparticles tend to be immobilized in mucus via steric and/or adhesive interactions. Contrary to the established opinion that poly(vinyl alcohol) (PVA) is mucoadhesive, we discovered that coating otherwise mucoadhesive nanoparticles with certain partially hydrolyzed PVAs can aid particle mobility in mucus. We describe two approaches to producing such mucus-penetrating particles (non-covalent modification of pre-formed nanoparticles and emulsification in the presence of PVA) and provide mobility data in human cervicovaginal mucus ex vivo as measured by multiple particle tracking and bulk permeation. When coated with PVAs that are ≥95% hydrolyzed, nanoparticles as small as ~210nm were immobilized in mucus similarly to well-established mucoadhesive controls (P>0.05). However, nanoparticles coated with PVAs that are <95% hydrolyzed penetrated mucus with velocities significantly exceeding those for the mucoadhesive controls (P<0.001) and were mobile in the bulk permeation assay.