Abstract
The aim of this study was to develop and evaluate a novel mucoadhesive drug delivery system based on thiolated poly(acrylic acid) nanoparticles exhibiting mucolytic properties to enhance particle diffusion into deeper mucus regions before adhesion. Mediated by a carbodiimide, cysteine and the mucolytic enzyme papain were covalently attached to poly(acrylic acid) via amide bond formation. The conjugates were co-precipitated with calcium chloride in order to obtain papain modified (PAA-pap) and thiolated nanoparticles (PAA-cys) as well as particles containing both conjugates (PAA-cys-pap). The nanoparticulate systems were characterized regarding particle size distribution and zeta potential. Particle transport was investigated by diffusion studies across intestinal mucus using two different techniques. Furthermore, mucoadhesive properties of all particles were evaluated via rheological measurements. Results demonstrated that all nanoparticles were in a size range of 158–214nm and showed negative zeta potentials. Due to the presence of papain, the PAA-cys-pap particles were capable of cleaving mucoglycoprotein substructures and consequently exhibited a 2.0-fold higher penetration into the mucus layer in comparison with PAA-cys particles. Within the rheological studies, an 1.9-fold increase in mucoadhesion could be achieved for the nanoparticulate system based on thiolated PAA compared to papain modified particles (PAA-pap). Therefore, the newly developed particulate system (PAA-cys-pap) is characterized by mucoadhesive as well as mucolytic properties. The combination of both effects – mucus-permeating and mucoadhesive properties – might be a promising strategy for the development of oral drug delivery systems to overcome the mucus barrier and providing a prolonged residence time close to the absorption membrane.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: European Journal of Pharmaceutics and Biopharmaceutics
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
