Enteric Coating Systems for the Oral Administration of Bioactive Calcium Phosphate Nanoparticles Carrying Nucleic Acids into the Colon

Abstract A system to deliver bioactive calcium phosphate nanoparticles (about 60 nm, loaded with nucleic acids) across the stomach into the colon was developed by freeze‐drying the nanoparticles in the presence of the cryoprotectant trehalose, incorporation into gelatin capsules, and coating the capsules with an enteric polymer. These capsules were stable at pH 1 (stomach conditions) and dissolved at pH 7.1 (colon conditions). The nanoparticles were released after about 60–120 min at pH 7.1. Cell culture experiments with HeLa and Caco‐2 cells showed an uptake of the nanoparticles, a transfection with EGFP‐encoding plasmid DNA, and a gene‐silencing with anti‐EGFP siRNA. From a variety of enteric coating polymers, the systems cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose‐Eudragit L100, and hydroxypropylmethylcellulose‐polyvinylalcohol‐Eudragit L100 were the most suitable to accomplish the desired biological effect. The presented method is applicable for colon therapy, e. g. for an oral administration of bioactive nanoparticles which are sensitive to acidic conditions.