Development and in vivo evaluation of papain-functionalized nanoparticles.

The aim of the present study was to develop a novel nanoparticulate delivery system being capable of penetrating the intestinal mucus layer by cleaving mucoglycoprotein substructures. Nanoparticles based on papain grafted polyacrylic acid (papain-g-PAA) were prepared via ionic gelation and labeled with fluorescein diacetate. In vitro, the proteolytic potential of papain modified nanoparticles was investigated by rheological measurements and diffusion studies across fresh porcine intestinal mucus. The presence of papain on the surface and inside the particles strongly decreases viscosity of the mucus leading to facilitated particle transition across the mucus layer. Results of the permeation studies revealed that enzyme grafted particles diffuse through mucus layer to a 3.0-fold higher extent than the same particles without enzyme. Furthermore, the penetration behavior of the nanocarriers along the gastrointestinal tract of Sprague Dawley rats was investigated after oral administration of nanoparticles formulated as enteric coated capsules. The majority of the papain functionalized particles was able to traverse across the mucus layer and remained in the duodenum and jejunum of the small intestine where drug absorption primarily occurs. Polymeric nanoparticles combined with mucolytic enzymes that are capable of overcoming intestinal mucus barriers offer an encouraging new attempt for mucosal drug delivery.