Benefits of pH-responsive polyelectrolyte coatings for carboxymethyl cellulose-based microparticles in the controlled release of esculin

Abstract

Moderate and prolonged payload release in response to a particular factor is highly demanded for efficient carriers of low-molecular-weight, chemically unstable phytopharmaceuticals. Thus, the objective of our contribution was to establish the effect of pH-responsive polyelectrolyte coatings on the release properties of carboxymethyl cellulose-based microparticles designed to deliver phytopharmaceuticals through the gastrointestinal tract. Microparticles were fabricated via extrusion coupled with external gelation and further coated with polyelectrolytes (PEs) (chitosan, gelatin, or PAH and PSS) involving electrostatic interactions. Successful deposition of PEs was confirmed by FTIR, and their thickness and viscosity were characterized in terms of QCM-D and ellipsometric techniques. The encapsulation efficiency of esculin, used as a model phytopharmaceutical, as proven by UV-Vis studies, was over 57%. SEM and fluorescence microscopy revealed a micrometric size, a mostly spherical shape and an altered topography of the investigated microcapsules. The physical stability of the microcapsules in media of various pH values was confirmed with CLSM and gravimetric studies. Studies on human gingival fibroblasts in vitro revealed that the obtained microparticles did not induce any cytotoxic effects. Payload release was monitored in situ by means of CLSM and ex situ under gastrointestinal conditions in vitro. Mathematical evaluation of the microparticle release profiles using classical models led to the establishment of a new hybrid model that revealed the mechanism behind esculin release. We demonstrated that the application of a polyelectrolyte shell onto CMC-based microspheres may provide controlled delivery of the payload, with its release triggered by the pH and ionic strength of the medium. These observations suggest that the release manner of small-molecule glycosides under gastrointestinal conditions can be tailored by careful selection of suitable materials to obtain biocompatible and functional hydrogel microparticles.

Keywords: Controlled release; Esculin; Hydrogel; Intestinal targeted delivery; Microparticle; pH-responsive polyelectrolyte coating.