Ionic Diffusion and Drug Release Behavior of Core-Shell-Functionalized Alginate-Chitosan-Based Hydrogel

Abstract

This paper reports the core-shell structure effects in calcium alginate (CaALG) microbeads due to the threshold water level for phase transition and correlates these properties with respect to pH and electrical conductivity. Further, in this study, we used a novel microfluidic device for drug release testing to study the programmed release of risedronate (RIS-anti-osteoporotic drug) encapsulated in pH-responsive CaALG-chitosan (CHT) microbeads. Our microfluidic device contains a single straight microchannel containing a steplike barrier design used to restrict the mobility of the microbeads at the sample detection zone. For optical and fluorescence microscopy, single fluorescently labeled CaALG-CHT microbead containing RIS was placed in the sample detection zone by flowing through the inlet port with ultrapure water. The RIS release behavior from the microbeads at different pH (2.1, 4, 6.8, and 7.4) conditions was determined by using a spectrophotometer connected to the outlet port of the device. Results of our first study showed that the decrease in the concentration of CaCl2 increases the swelling rate in CaALG microbeads. Maximum swelling was achieved with the lowest molar concentration of CaCl2 used for fabrication of CaALG microbeads. Further, electrical current-voltage characteristic shows the nature of ionic mobility with respect to varying levels of pH indicating electrokinetic forces developed in the CaALG microbeads. By using a microfluidic device for drug release testing, we demonstrated that a sustained release delivery system for RIS can be prepared by coating with pH-sensitive and biodegradable CaALG-CHT. The CaALG-CHT microbeads used for encapsulating RIS are resistant to the acidic environment of the stomach. This may improve the therapeutic effectiveness and reduce the gastric adverse effects associated with RIS by preventing its decomposition in the acidic condition of stomach. The newly developed microfluidic device for drug release testing may find applications in screening novel drugs and delivery systems.