Suppositories with bioactive calcium phosphate nanoparticles for intestinal transfection and gene silencing

Abstract

Calcium phosphate nanoparticles (diameter about 60 nm, triple‐shell) were loaded with nucleic acids (DNA or siRNA) for local gene therapy in the colon. To avoid the oral administration where a passage through the stomach is necessary, the nanoparticles were incorporated into custom‐made hard‐fat suppositories after freeze‐drying with trehalose. After melting the suppository at 37°C, the nanoparticles were released and well dispersed in cell culture medium. They retained their bioactivity as shown by in vitro cell culture studies with the model cell line HeLa and the colon cancer cell line Caco‐2. The nanoparticles were easily taken up by both cell types and also efficient for transfection and gene silencing, as shown with the model protein eGFP. This opens a way for local gene therapy in the colon.