Triborheological analysis of reconstituted gastrointestinal porcine mucus / chitosan:TPP nanoparticles system for studying mucoadhesion under different pH conditions

Abstract

The use of biodegradable polymers as vehicles for administration and long-term release of drugs has great relevance in the delivery of new generation therapeutic agents, such as: amino acids, peptides, proteins, antibodies, nucleic acids, among others. Because biomolecules are metabolized or excreted after short periods within the body, which are usually shorter than time required to observe their therapeutic effect or to reach the site of action. For that reason, the encapsulation of biomolecules in microspheres or nanoparticles represents a method of interest for biopharmaceuticals administration. Additionally, the phenomenon of mucoadhesion has been studied as an alternative to increase the residence time of nanocarriers within the body and, consequently, increase the half-life and cell permeability of biomolecules, allowing them to reach the level of bioavailability necessary to carry out its therapeutic activity when administered orally. Chitosan nanoparticles were analyzed as a possible mucoadhesive vehicle for drug delivery based on their cationic nature that exhibits a high degree of interaction with negatively charged mucus functional groups. However, chitosan presents significant changes in its surface charge throughout the gastrointestinal tract due to variations in pH, affecting its mucoadhesive properties. This project proposed the analysis of the interaction between reconstituted gastrointestinal porcine mucus and chitosan:TPP nanoparticles under gastrointestinal pH conditions (pH = 2.0 – 7.0) from a triborheological point of view. Considering that rheological synergism represents an indirect method to evaluate the presence or absence of mucoadhesion phenomenon based on the strength of the interfacial layer between mucus and nanoparticles, which is measured by the increase of viscosity (η) or elastic modulus (G’) in the mixture of mucus-nanoparticles as a result of the interpenetration of polymeric and mucin chains through electrostatic interactions and physical entanglement, mainly. Therefore, triborheological tests were performed to characterize the viscoelastic, viscous, and lubricating profiles of reconstituted mucus at different pH conditions to examine the variations experienced by the mucus along the gastrointestinal tract. Similarly, triborheological synergism analyzes were performed to determine under which pH values the mucoadhesion phenomenon occurs, revealing that chitosan:TPP exhibit mucoadhesiveness at conditions below its value of pKa (6.5). Whereas, under neutral environment or above to their pKa value, chitosan:TPP nanoparticles do not exhibit the mucoadhesion properties.