Ca-Alginate-Based Janus Capsules with a Pumping Effect for Intestinal-Targeted Controlled Release

Abstract

A novel intestinal-targeted θ-shaped capsule with a pumping effect for the controlled release of hydrophobic drugs is successfully developed. The proposed capsule is composed of a Ca-alginate–chitosan/protamine/silica (ACPSi) composite shell and two chambers forming a θ-shape (θ-ACPSi), which respectively encapsulate drugs and booster agents. Enteric hydroxypropyl methylcellulose phthalate (HPMCP) microspheres are embedded into the drug chamber shell. The θ-ACPSi composite shell offers improved protection for the encapsulated drug in the stomach environment and excellent intestinal-targeted drug release. Using indomethacin as the model drug and polyacrylic acid (PAA) as the booster agent, both the opening of “microchannels” in the drug chamber and the swelling of PAA in the booster chamber increase the release rate of high-concentration indomethacin and ensure a constant release of indomethacin in the small intestine. In the stomach (pH 2.5), less than 1% of the indomethacin is released. However, when the θ-ACPSi capsules enter the small intestine (pH 6.8), the HPMCP microspheres in the drug chamber shell dissolve to open the “microchannels,” while the PAA swells to provide pumping impetus. As a result, more than 60% of the indomethacin is released at a constant speed in the small intestine. The proposed θ-ACPSi capsules provide a potential and novel model for developing responsive pumping controlled-release systems and intestinal-targeted drug delivery systems.

Keywords

• Capsules
• Ca-alginate
• Intestinal-targeted delivery
• Pumping effects
• Controlled release